The weakness from LEMS typically involves the muscles of the proximal arms and legs (the muscles closer to the trunk). In contrast to myasthenia gravis, the weakness affects the legs more than the arms. This leads to difficulties climbing stairs and rising from a sitting position. Weakness is often relieved temporarily after exertion or physical exercise. High temperatures can worsen the symptoms. Weakness of the bulbar muscles (muscles of the mouth and throat) is occasionally encountered. Weakness of the eye muscles is uncommon. Some may have double vision, drooping of the eyelids and difficulty swallowing, but generally only together with leg weakness; this too distinguishes LEMS from myasthenia gravis, in which eye signs are much more common. In the advanced stages of the disease, weakness of the respiratory muscles may occur. Some may also experience problems with coordination (ataxia).

Three-quarters of people with LEMS also have disruption of the autonomic nervous system. This may be experienced as a dry mouth, constipation, blurred vision, impaired sweating, and orthostatic hypotension (falls in blood pressure on standing, potentially leading to blackouts). Some report a metallic taste in the mouth.

On neurological examination, the weakness demonstrated with normal testing of power is often less severe than would be expected on the basis of the symptoms. Strength improves further with repeated testing, e.g. improvement of power on repeated hand grip (a phenomenon known as "Lambert's sign"). At rest, reflexes are typically reduced; with muscle use, reflex strength increases. This is a characteristic feature of LEMS. The pupillary light reflex may be sluggish.

In LEMS associated with lung cancer, most have no suggestive symptoms of cancer at the time, such as cough, coughing blood, and unintentional weight loss. LEMS associated with lung cancer may be more severe.

Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder characterized by muscle weakness of the limbs. It is the result of an autoimmune reaction in which antibodies are formed against presynaptic voltage-gated calcium channels, and likely other nerve terminal proteins, in the neuromuscular junction (the connection between nerves and the muscle that they supply). The prevalence is 3.4 cases per million. Around 60% of those with LEMS have an underlying malignancy, most commonly small-cell lung cancer; it is therefore regarded as a paraneoplastic syndrome (a condition that arises as a result of cancer elsewhere in the body).

LEMS usually occurs in people over 40 years of age, but may occur at any age. The diagnosis is usually confirmed with electromyography and blood tests; these also distinguish it from myasthenia gravis, a related autoimmune neuromuscular disease.

If the disease is associated with cancer, direct treatment of the cancer often relieves the symptoms of LEMS. Other treatments often used are steroids, azathioprine, which suppress the immune system, intravenous immunoglobulin, which outcompetes autoreactive antibody for Fc receptors, and pyridostigmine and 3,4-diaminopyridine, which enhance the neuromuscular transmission. Occasionally, plasma exchange is required to remove the antibodies.

The initial, main symptom in MG is painless weakness of specific muscles, not fatigue. The muscle weakness becomes progressively worse during periods of physical activity and improves after periods of rest. Typically, the weakness and fatigue are worse toward the end of the day. MG generally starts with ocular (eye) weakness; it might then progress to a more severe generalized form, characterized by weakness in the extremities or in muscles that govern basic life functions.

Weakness of the muscles involved in speaking may lead to dysarthria and hypophonia. Speech may be slow and slurred, or have a nasal quality. In some cases, a singing hobby or profession must be abandoned.

Immune-mediated diseases include a variety of diseases not only affecting the neuromuscular junction. Immune-mediated disorders range from simple and common problems such as allergies to disorders such as HIV/AIDS. Within this classification, autoimmune disorders are considered to be a subset of immune-mediated syndromes. Autoimmune diseases occur when the body's immune system begins to target its own cells, often causing harmful effects.

The neuromuscular junction diseases present within this subset are myasthenia gravis, and Lambert-Eaton syndrome.(reference 26) In each of these diseases, a receptor or other protein essential to normal function of the junction is targeted by antibodies in an autoimmune attack by the body.

Metabolic diseases are usually a result of abnormal functioning of one of the metabolic processes required for regular production and utilization of energy in a cell. This can occur by damaging or disabling an important enzyme, or when a feedback system is abnormally functioning. Toxic diseases are a result of a form of poison that effects neuromuscular junction functioning. Most commonly animal venom or poison, or other toxic substances are the origin of the problem.

Neuromuscular junction diseases in this category include snake venom poisoning, botulism, arthropod poisoning, organophosphates and hypermagnesemia.(reference 13) Organophosphates are present in many insecticides and herbicides. They are also the basis of many nerve gases.(reference 27) Hypermagnesmia is a condition where the balance of magnesium in the body is unstable and concentrations are higher than normal baseline values.(reference 28)

NMT is a diverse disorder. As a result of muscular hyperactivity, patients may present with muscle cramps, stiffness, myotonia-like symptoms (slow relaxation), associated walking difficulties, hyperhidrosis (excessive sweating), myokymia (quivering of a muscle), fasciculations (muscle twitching), fatigue, exercise intolerance, myoclonic jerks and other related symptoms. The symptoms (especially the stiffness and fasciculations) are most prominent in the calves, legs, trunk, and sometimes the face and neck, but can also affect other body parts. NMT symptoms may fluctuate in severity and frequency. Symptoms range from mere inconvenience to debilitating. At least a third of people also experience sensory symptoms.

There are three main types of NMT:

- Chronic

- Monophasic (symptoms that resolve within several years of onset; postinfection, postallergic)

- Relapsing Remitting

The following diseases manifest by means of neurological dysfunction: Lambert-Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration, encephalomyelitis, limbic encephalitis, brainstem encephalitis, opsoclonus myoclonus ataxia syndrome, anti-NMDA receptor encephalitis, and polymyositis.

The types of CMS are classified into three categories: presynaptic, postsynaptic, and synaptic.

- "Presynaptic" symptoms include brief stops in breathing, weakness of the eye, mouth, and throat muscles. These symptoms often result in double vision and difficulty chewing and swallowing.

- "Postsynaptic" symptoms in infants include severe muscle weakness, feeding and respiratory problems, and delays in the ability to sit, crawl, and walk.

- "Synaptic" symptoms include early childhood feeding and respiratory problems, reduced mobility, curvature of the spine, and weakness, which causes a delay in motor milestones.

Onset symptoms for all ages may include droopy eyelids. A particular form of postsynaptic CMS (slow-channel CMS) includes severe weakness beginning in infancy or childhood that progresses and leads to loss of mobility and respiratory problems in adolescence or later life.

The following diseases manifest by means of mucocutaneous dysfunction: acanthosis nigricans, dermatomyositis, Leser-Trélat sign, necrolytic migratory erythema, Sweet's syndrome, Florid cutaneous papillomatosis, pyoderma gangrenosum, and acquired generalized hypertrichosis. Mucocutaneous dysfunctions of paraneoplastic syndromes can be seen in cases of itching (hypereosinophilia), immune system depression (latent varicella-zoster virus in sensory ganglia), pancreatic tumors (leading to adipose nodular necrosis of subcutaneous tissues, flushes (prostaglandin secretions), and even dermic melanosis (cannot be eliminated via urine and results in grey to black-blueish skin tones).

Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several types at the neuromuscular junction. The effects of the disease are similar to Lambert-Eaton Syndrome and myasthenia gravis, the difference being that CMS is not an autoimmune disorder.

The ‘Harlequin Sign’ is unilateral flushing and sweating of the face, neck, and upper chest usually after exposure to heat or strenuous exertion. Horner syndrome, another problem associated with the sympathetic nervous system, is often seen in conjunction with harlequin syndrome.

Since Harlequin syndrome is associated with a dysfunction in the autonomic nervous system, main symptoms of this dysfunction are in the following: Absence of sweat(anhidrosis) and flushing on one side of the face, neck, or upper thoracic area. In addition, other symptoms include cluster headaches, tearing of the eyes, nasal discharge, abnormal contraction of the pupils, weakness in neck muscles, and drooping of on side of the upper eyelid.

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)

One possible cause of Harlequin syndrome is a lesion to the preganglionic or postganglionic cervical sympathetic fibers and parasympathetic neurons of the ciliary ganglion. It is also believed that torsion (twisting) of the thoracic spine can cause blockage of the anterior radicular artery leading to Harlequin syndrome. The sympathetic deficit on the denervated side causes the flushing of the opposite side to appear more pronounced. It is unclear whether or not the response of the undamaged side was normal or excessive, but it is believed that it could be a result of the body attempting to compensate for the damaged side and maintain homeostasis.

Since the cause and mechanism of Harlequin syndrome is still unknown, there is no way to prevent this syndrome.

In patients that have already been diagnosed with sarcoidosis, Heerfordt syndrome can be inferred from the major symptoms of the syndrome, which include parotitis, fever, and facial nerve palsy. In cases of parotitis, ultrasound-guided biopsy is used to exclude the possibility of lymphoma. There are many possible causes of facial nerve palsy, including Lyme disease, HIV, Melkersson–Rosenthal syndrome, schwannoma, and Bell's palsy. Heerfordt syndrome exhibits spontaneous remission. Treatments for sarcoidosis include corticosteroids and immunosuppressive drugs.

The Kocher–Debré–Semelaigne syndrome is hypothyroidism in infancy or childhood characterised by lower extremity or generalized muscular hypertrophy, myxoedema, short stature and cretinism. The absence of painful spasms and pseudomyotonia differentiates this syndrome from its adult form, which is Hoffmann syndrome.

The syndrome is named after Emil Theodor Kocher, Robert Debré and Georges Semelaigne.

Also known as Debre–Semelaigne syndrome or cretinism-muscular hypertrophy, hypothyroid myopathy, hypothyroidism-large muscle syndrome, hypothyreotic muscular hypertrophy in children, infantile myxoedema-muscular hypertrophy, myopathy-myxoedema syndrome, myxoedema-muscular hypertrophy syndrome, myxoedema-myotonic dystrophy syndrome.

Kocher-Debre-Semelaigne syndrome gives infant a Hercules appearance.

Heerfordt syndrome, also referred to as uveoparotid fever, Heerfordt–Mylius syndrome, Heerfordt–Waldenström syndrome, and Waldenström's uveoparotitis, is a rare manifestation of sarcoidosis. The symptoms include inflammation of the eye (uveitis), swelling of the parotid gland, chronic fever, and in some cases, of the facial nerves.

Hyporeflexia refers to below normal or absent reflexes (areflexia). It can be detected through the use of a reflex hammer. It is the opposite of hyperreflexia.

Hyporeflexia is generally associated with a lower motor neuron deficit (at the alpha motor neurons from spinal cord to muscle), whereas hyperreflexia is often attributed to upper motor neuron lesions (along the long, motor tracts from the brain). The upper motor neurons are thought to inhibit the reflex arc, which is formed by sensory neurons from intrafusal fibers of muscles, lower motor neurons (including alpha and gamma motor fibers) and appurtenant interneurons. Therefore, damage to lower motor neurons will subsequently result in hyporeflexia and/or areflexia.

Note that, in spinal shock, which is commonly seen in the transection of the spinal cord (Spinal cord injury), areflexia can transiently occur below the level of the lesion and can , after some time, become hyperreflexic. Furthermore, cases of severe muscle atrophy or destruction could render the muscle too weak to show any reflex and should not be confused with a neuronal cause.

Hyporeflexia may have other causes, including hypothyroidism, electrolyte imbalance (e.g. excess magnesium), drug induced (e.g. the symptoms of benzodiazepine intoxication include confusion, slurred speech, ataxia, drowsiness, dyspnea, and hyporeflexia).

Diseases associated with hyporeflexia include

- Centronuclear myopathy

- Guillain–Barré syndrome

- Lambert-Eaton myasthenic syndrome

- Polyneuropathy (Achilles and plantar reflexes)

Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) is a peripheral neuropathy, a disorder of the nerves. HNPP is a nerve disorder that affects the peripheral nerves,—pressure on the nerves can cause tingling sensations, numbness, pain, weakness, muscle atrophy, and even paralyzation of affected area. In normal individuals these symptoms disappear quickly but in sufferers of HNPP even a short period of pressure can cause the symptoms to occur. Palsies can last from minutes, days to weeks, or even months.

The symptoms may vary—some individuals report minor problems, whilst others experience severe discomfort and disability. In many cases the symptoms are mild enough to go unnoticed. The time period between episodes is known to vary between individuals. HNPP has not been found to alter the lifespan, although in some cases a decline in quality of life is noticed. Some sufferers (10-15%) report various pains growing in severity with progression of the disease. The nerves most commonly affected are the peroneal nerve at the fibular head (leg and feet), the ulnar nerve at the elbow (arm), and the median nerve at the wrist (palm, thumbs and fingers), but any peripheral nerve can be affected. HNPP is part of the group of hereditary motor and sensory neuropathy (HMSN) disorders and is linked to Charcot–Marie–Tooth disease (CMT).

Romano–Ward syndrome presents the following in an affected individual:

- Ventricular fibrillation

- Syncope

- Torsade de pointes

- Abnormality of ear

The syndrome is a rare clinical disorder.

- Physical

- Overgrowth

- Accelerated skeletal maturation

- Dysmorphic facial features

- Prominent eyes

- Bluish sclerae

- Coarse eyebrows

- Upturned nose

- Radiologic examination

- Accelerated osseous maturation

- Phalangeal abnormalities

- Tubular thinning of the long bones

- Skull abnormalities

- Mental

- Often associated with intellectual disability (of variable degree)

Romano–Ward syndrome is the major variant of "long QT syndrome". It is a condition that causes a disruption of the heart's normal rhythm. This disorder is a form of long QT syndrome, which is a heart condition that causes the cardiac muscle to take longer than usual to recharge between beats; if untreated, the irregular heartbeats can lead to fainting, seizures, or sudden death

Among the signs/symptoms of hereditary neuropathy with liability to pressure palsy are the following (different symptoms are caused by different nerves, such as the "foot drop" is caused by the "peroneal nerve"):