Diagnostic procedures that may reveal muscular disorders include direct clinical observations. This usually starts with the observation of bulk, possible atrophy or loss of muscle tone. Neuromuscular disease can also be diagnosed by testing the levels of various chemicals and antigens in the blood, and using electrodiagnostic medicine tests including electromyography (measuring electrical activity in muscles) and nerve conduction studies.

In neuromuscular disease evaluation, it is important to perform musculoskeletal and neurologic examinations. Genetic testing is an important part of diagnosing inherited neuromuscular conditions.

In terms of treatment for neuromuscular diseases (NMD), "exercise" might be a way of managing them, as NMD individuals would gain muscle strength. In a study aimed at results of exercise, in muscular dystrophy and Charcot-Marie-Tooth disease, the later benefited while the former did not show benefit; therefore, it depends on the disease Other management routes for NMD should be based on medicinal and surgical procedures, again depending on the underlying cause.

In regards to the diagnosis of spinal and bulbar muscular atrophy, the "AR Xq12" gene is the focus. Many mutations are reported and identified as missense/nonsense, that can be identified with 99.9% accuracy. Test for this gene in the majority of affected patients yields the diagnosis.

Diagnosis is clinical and initially consists of ruling out more common conditions, disorders, and diseases, and usually begins at the general practitioner level. A doctor may conduct a basic neurological exam, including coordination, strength, reflexes, sensation, etc. A doctor may also run a series of tests that include blood work and MRIs.

From there, a patient is likely to be referred to a neurologist or a neuromuscular specialist. The neurologist or specialist may run a series of more specialized tests, including needle electromyography EMG/ and nerve conduction studies (NCS) (these are the most important tests), chest CT (to rule out paraneoplastic) and specific blood work looking for voltage-gated potassium channel antibodies, acetylcholine receptor antibody, and serum immunofixation, TSH, ANA ESR, EEG etc. Neuromyotonia is characterized electromyographically by doublet, triplet or multiplet single unit discharges that have a high, irregular intraburst frequency. Fibrillation potentials and fasciculations are often also present with electromyography.

Because the condition is so rare, it can often be years before a correct diagnosis is made.

NMT is not fatal and many of the symptoms can be controlled. However, because NMT mimics some symptoms of motor neuron disease (ALS) and other more severe diseases, which may be fatal, there can often be significant anxiety until a diagnosis is made. In some rare cases, acquired neuromyotonia has been misdiagnosed as amyotrophic lateral sclerosis (ALS) particularly if fasciculations may be evident in the absence of other clinical features of ALS. However, fasciculations are rarely the first sign of ALS as the hallmark sign is weakness. Similarly, multiple sclerosis has been the initial misdiagnosis in some NMT patients. In order to get an accurate diagnosis see a trained neuromuscular specialist.

Congenital myasthenic syndromes (CMS) is "often difficult to diagnose because of a broad differential diagnosis and lack of specific laboratory findings. Identification of the underlying mutation is critical, as certain mutations lead to treatment-responsive conditions while others do not." Whole exome sequencing (WES) is often used as a diagnostic tool that allows for the "initiation of specific treatment".

Treatment depends on the form (category) of the disease. Although symptoms are similar to myasthenia gravis, treatments used in MG are not useful in CMS. MG is treated with immunosuppressants, but CMS is not an autoimmune disorder. Instead, CMS is genetic and responds to other forms of drug treatments.

A form of presynaptic CMS is caused by an insufficient release of acetylcholine (ACh) and is treated with cholinesterase inhibitors.

Postsynaptic fast-channel CMS (ACh receptors do not stay open long enough) is treated with cholinesterase inhibitors and 3,4-diaminopyridine. In the U.S., the more stable phosphate salt formulation of 3,4-diaminopyridine (amifampyridine phosphate) is under development as an orphan drug for CMS and is available to eligible patients at no cost under an expanded access program by Catalyst Pharmaceuticals.

Postsynaptic slow-channel CMS is treated with quinidine or fluoxetine, which plugs the ACh receptor.

Ephedrine has been tested on patients in clinical trials and appears to be an effective treatment for DOK7 CMS. Most patients tolerate this type of treatment and improvements in strength can be impressive. Further research must be done in order to determine the long-term response of ephedrine as well as the most effective dosage regimen. Ephedrine can lead to a profound improvement in muscle strength and an even more impressive effect on day-to-day function. The effect of ephedrine is delayed and the improvement occurs over a period of months. Ephedrine was given at doses between 15 and 90 mg/day and as a result, muscle strength improved

A 2006 study followed 223 patients for a number of years. Of these, 15 died, with a median age of 65 years. The authors tentatively concluded that this is in line with a previously reported estimate of a shortened life expectancy of 10-15 years (12 in their data).

Benign fasciculation syndrome is a diagnosis of exclusion; that is, other potential causes for the twitching (mostly forms of neuropathy or motor neuron diseases such as ALS) must be ruled out before BFS can be assumed. An important diagnostic tool here is electromyography (EMG). Since BFS appears to cause no actual nerve damage (at least as seen on the EMG), patients will likely exhibit a completely normal EMG (or one where the only abnormality seen is fasciculations).

Another important step in diagnosing BFS is checking the patient for clinical weakness. Clinical weakness is often determined through a series of strength tests, such as observing the patient's ability to walk on his or her heels and toes. Resistance strength tests may include raising each leg, pushing forward and backward with the foot and/or toes, squeezing with fingers, spreading fingers apart, and pushing with or extending arms and/or hands. In each such test the test provider will apply resisting force and monitor for significant differences in strength abilities of opposing limbs or digits. If such differences are noted or the patient is unable to apply any resisting force, clinical weakness may be noted.

Lack of clinical weakness along with normal EMG results (or those with only fasciculations) largely eliminates more serious disorders from potential diagnosis.

Especially for younger persons who have only LMN sign fasciculations, "In the absence of weakness or abnormalities of thyroid function or electrolytes, individuals under 40 years can be reassured without resorting to electromyography (EMG) to avoid the small but highly damaging possibility of false-positives". "Equally, however, most subspecialists will recall a small number of cases, typically men in their 50s or 60s, in whom the latency from presentation with apparently benign fasciculations to weakness (and then clear MND) was several years. Our impression is that a clue may be that the fasciculations of MND are often abrupt and widespread at onset in an individual previously unaffected by fasciculations in youth. The site of the fasciculations, for example, those in the calves versus abdomen, has not been shown to be discriminatory for a benign disorder. There is conflicting evidence as to whether the character of fasciculations differs neurophysiologically in MND".

Another abnormality commonly found upon clinical examination is a brisk reflex action known as "hyperreflexia". Standard laboratory tests are unremarkable. According to neurologist John C. Kincaid:

Neuromyotonia is a type of peripheral nerve hyperexcitability. Peripheral nerve hyperexcitability is an umbrella diagnosis that includes (in order of severity of symptoms from least severe to most severe) benign fasciculation syndrome, cramp fasciculation syndrome, and neuromyotonia. Some doctors will only give the diagnosis of peripheral nerve hyperexcitability as the differences between the three are largely a matter of the severity of the symptoms and can be subjective. However, some objective EMG criteria have been established to help distinguish between the three.

Moreover, the generic use of the term "peripheral nerve hyperexcitability syndromes" to describe the aforementioned conditions is recommended and endorsed by several prominent researchers and practitioners in the field.

Mitochondrial diseases are usually detected by analysing muscle samples, where the presence of these organelles is higher. The most common tests for the detection of these diseases are:

1. Southern blot to detect big deletions or duplications

2. PCR and specific mutation analysis

3. Sequencing

There are two ways to classify neuromuscular diseases. The first relies on its mechanism of action, or how the action of the diseases affects normal functioning (whether it is through mutations in genes or more direct pathways such as poisoning). This category divides neuromuscular diseases into three broad categories: immune-mediated disease, toxic/metabolic and congenital syndromes.

The second classification method divides the diseases according to the location of their disruption. In the neuromuscular junction, the diseases will either act on the presynaptic membrane of the motor neuron, the synapse separating the motor neuron from the muscle fiber, or the postsynaptic membrane (the muscle fiber).

Congenital syndromes affecting the neuromuscular junction are considered a very rare form of disease, occurring in 1 out of 200,000 in the United Kingdom.(reference 29) These are genetically inherited disorders. Symptoms are seen early since the affected individuals carry the mutation from birth. Congenital syndromes are usually classified by the location of the affected gene products. Congenital syndromes can have multiple targets affecting either the presynaptic, synaptic or postsynaptic parts of the neuromuscular junction.(reference 30) For example, if the malfunctioning or inactive protein is acetylcholinesterase, this would be classified as a synapse congenital syndrome.(reference 29)

If the diagnosis is suspected, serology can be performed:

- One test is for antibodies against the acetylcholine receptor; the test has a reasonable sensitivity of 80–96%, but in ocular myasthenia, the sensitivity falls to 50%.

- A proportion of the patients without antibodies against the acetylcholine receptor have antibodies against the MuSK protein.

- In specific situations, testing is performed for Lambert-Eaton syndrome.

A chest X-ray may identify widening of the mediastinum suggestive of thymoma, but computed tomography or magnetic resonance imaging (MRI) are more sensitive ways to identify thymomas and are generally done for this reason. MRI of the cranium and orbits may also be performed to exclude compressive and inflammatory lesions of the cranial nerves and ocular muscles.

Initial screening for CIP/CIM may be performed using an objective scoring system for muscle strength. The Medical Research Council (MRC) score is one such tool, and sometimes used to help identify CIP/CIM patients in research studies. The MRC score involves assessing strength in 3 muscle groups in the right and left sides of both the upper and lower extremities. Each muscle tested is given a score of 0-5, giving a total possible score of 60. An MRC score less than 48 is suggestive of CIP/CIM. However, the tool requires that patients be awake and cooperative, which is often not the case. Also, the screening tool is non-specific, because it does not identify the cause a person's muscle weakness.

Once weakness is detected, the evaluation of muscle strength should be repeated several times. If the weakness persists, then a muscle biopsy, a nerve conduction study (electrophysiological studies), or both should be performed.

There is no cure for PMD, nor is there a standard course of treatment. Treatment, which is symptomatic and supportive, may include medication for seizures and spasticity. Regular evaluations by physical medicine and rehabilitation, orthopedic, developmental and neurologic specialists should be made to ensure optimal therapy and educational resources. The prognosis for those with Pelizaeus–Merzbacher disease is highly variable, with children with the most severe form (so-called connatal) usually not surviving to adolescence, but survival into the sixth or even seventh decades is possible, especially with attentive care. Genetic counseling should be provided to the family of a child with PMD.

In December 2008, StemCells Inc., a biotech company in Palo Alto, received clearance from the U.S. Food and Drug Administration (FDA) to conduct Phase I clinical trials in PMD to assess the safety of transplanting human neural stem cells as a potential treatment for PMD. The trial was initiated in November 2009 at the University of California, San Francisco (UCSF) Children's Hospital.

The serum creatine phosphokinase (CPK) can be mildly elevated. While the CPK is often a good marker for damage to muscle tissue, it is not a helpful marker in CIP/CIM, because CIP/CIM is a gradual process and does not usually involve significant muscle cell death (necrosis). Also, even if necrosis is present, it may be brief and is therefore easily missed. If a lumbar puncture (spinal tap) is performed, the protein level in the cerebral spinal fluid would be normal.

Amniocentesis or chorionic villus sampling can be used to screen for the disease before birth. After birth, urine tests, along with blood tests and skin biopsies can be used to diagnose Schindler disease. Genetic testing is also always an option, since different forms of Schindler disease have been mapped to the same gene on chromosome 22; though different changes (mutations) of this gene are responsible for the infantile- and adult-onset forms of the disease.

The diagnosis is usually made on electromyography (EMG), which is one of the standard tests in the investigation of otherwise unexplained muscle weakness. This involves the insertion of small needles into the nerves supplying several muscles, administering small electrical impulses through these needles, and measuring the electrical response of the muscle in question. Two EMG investigations can be characteristic in LEMS: compound motor action potentials (CMAPs) and single-fiber examination.

CMAPs show small amplitudes but normal latency and conduction velocities. If repeated impulses are administered (2 per second or 2 Hz), it is normal for CMAP amplitudes to become smaller as the acetylcholine in the motor end plate is depleted. In LEMS, this decrease is larger than observed normally. Eventually, stored acetylcholine is made available, and the amplitudes increase again. In LEMS, this remains insufficient to reach a level sufficient for transmission of an impulse from nerve to muscle; all can be attributed to insufficient calcium in the nerve terminal. A similar pattern is witnessed in myasthenia gravis. In LEMS, in response to exercising the muscle, the CMAP amplitude increases greatly (over 200%, often much more). This also occurs on the administration of a rapid burst of electrical stimuli (20 impulses per second for 10 seconds). This is attributed to the influx of calcium in response to these stimuli. On single-fiber examination, features may include increased jitter (seen in other diseases of neuromuscular transmission) and blocking.

Blood tests may be performed to exclude other causes of muscle disease (elevated creatine kinase may indicate a myositis, and abnormal thyroid function tests may indicate thyrotoxic myopathy). Antibodies against voltage-gated calcium channels can be identified in 85% of people with EMG-confirmed LEMS. Once LEMS is diagnosed, investigations such as a CT scan of the chest are usually performed to identify any possible underlying lung tumors. Around 50–60% of these are discovered immediately after the diagnosis of LEMS. The remainder is diagnosed later, but usually within two years and typically within four years. As a result, scans are typically repeated every six months for the first two years after diagnosis. While CT of the lungs is usually adequate, a positron emission tomography scan of the body may also be performed to search for an occult tumour, particularly of the lung.

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 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.

Infants with Schindler disease tend to die within 4 years of birth, therefore, treatment for this form of the disease is mostly palliative. However, Type II Schindler disease, with its late onset of symptoms, is not characterized by neurological degeneration. There is no known cure for Schindler disease, but bone marrow transplants have been trialed, as they have been successful in curing other glycoprotein disorders.

Because different types of myopathies are caused by many different pathways, there is no single treatment for myopathy. Treatments range from treatment of the symptoms to very specific cause-targeting treatments. Drug therapy, physical therapy, bracing for support, surgery, and massage are all current treatments for a variety of myopathies.

The disease is one in a group of genetic disorders collectively known as leukodystrophies that affect growth of the myelin sheath, the fatty covering—which acts as an insulator—on nerve fibers in the CNS. PMD is generally caused by a recessive mutation of the gene on the long arm of the X-chromosome (Xq21-22) that codes for a myelin protein called proteolipid protein 1 or PLP1.

The onset of Pelizaeus–Merzbacher disease is usually in early infancy. The most characteristic early signs are nystagmus (rapid, involuntary, rhythmic motion of the eyes) and hypotonia (low muscle tone). Motor abilities are delayed or never acquired, mostly depending upon the severity of the mutation. Most children with PMD learn to understand language, and usually have some speech. Other signs may include tremor, lack of coordination, involuntary movements, weakness, unsteady gait, and over time, spasticity in legs and arms. Muscle contractures (shrinkage or shortening of a muscle) often occur over time. Mental functions may deteriorate. Some patients may have convulsions and skeletal deformation, such as scoliosis, resulting from abnormal muscular stress on bones.

There are several forms of Pelizaeus–Merzbacher disease including classic, connatal, transitional, and adult variants. The majority of disease-causing mutations result in duplications of the entire PLP1 gene. Interestingly, deletions at the PLP1 locus (which are rarer) cause a milder form of PMD than is observed with the typical duplication mutations, which demonstrates the critical importance of gene dosage at this locus for normal CNS function. Some of the remaining cases of PMD are accounted for by mutations in the gap junction A12 ("GJA12") gene, and are now called Pelizaeus-Merzbacher-like disease (PMLD). Other cases of apparent PMD do not have mutations in either the "PLP1" or "GJA12" genes, and are presumed to be caused either by mutations in other genes, or by mutations not detected by sequencing the "PLP1" gene exons and neighboring intronic regions of the gene. Among these is a new genetic disorder (discovered in 2003, 2004) which is caused by mutation in the transporter of thyroid hormone, MCT8, also known as SLC16A2, is believed to be account for a significant fraction of the undiagnosed neurological disorders (usually resulting in hypotonic/floppy infants with delayed milestones). This genetic defect was known as Allan–Herndon–Dudley syndrome (since 1944) without knowing its actual cause. Some of the signs for this disorder are as follows: normal to slightly elevated TSH, elevated T and reduced T (ratio of T/T is about double its normal value). Normal looking at birth and for the first few years, hypotonic (floppy), in particular difficulty to hold the head, possibly difficulty to thrive, possibly with delayed myelination (if so, some cases are reported with an MRI pattern similar to Pelizaeus–Merzbacher disease, known as PMD,) possibly with decreased mitochondrial enzyme activities, possibly with fluctuating lactate level. Patients have an alert face, a limited IQ, patients may never talk/walk, 50% need feeding tube, patients have a normal life span. MCT8 can be ruled out with a simple TSH/T/T thyroid test.

Milder mutations of the "PLP1" gene that mainly cause leg weakness and spasticity, with little or no cerebral involvement, are classified as spastic paraplegia 2 (SPG2).

Spindle transfer, where the nuclear DNA is transferred to another healthy egg cell leaving the defective mitochondrial DNA behind, is a potential treatment procedure that has been successfully carried out on monkeys. Using a similar pronuclear transfer technique, researchers at Newcastle University led by Douglass Turnbull successfully transplanted healthy DNA in human eggs from women with mitochondrial disease into the eggs of women donors who were unaffected. In such cases, ethical questions have been raised regarding biological motherhood, since the child receives genes and gene regulatory molecules from two different women. Using genetic engineering in attempts to produce babies free of mitochondrial disease is controversial in some circles and raises important ethical issues. A male baby was born in Mexico in 2016 from a mother with Leigh syndrome using spindle transfer.

In September 2012 a public consultation was launched in the UK to explore the ethical issues involved. Human genetic engineering was used on a small scale to allow infertile women with genetic defects in their mitochondria to have children.

In June 2013, the United Kingdom government agreed to develop legislation that would legalize the 'three-person IVF' procedure as a treatment to fix or eliminate mitochondrial diseases that are passed on from mother to child. The procedure could be offered from 29 October 2015 once regulations had been established.

Embryonic mitochondrial transplant and protofection have been proposed as a possible treatment for inherited mitochondrial disease, and allotopic expression of mitochondrial proteins as a radical treatment for mtDNA mutation load.

Currently, human clinical trials are underway at GenSight Biologics (ClinicalTrials.gov # NCT02064569) and the University of Miami (ClinicalTrials.gov # NCT02161380) to examine the safety and efficacy of mitochondrial gene therapy in Leber's hereditary optic neuropathy.

This condition is usually diagnosed by direct examination of the larynx under light sedation, which also allows checking for benign or malignant tumors. Tests, such as thoracic radiographs, CT-scans, or echocardiography, are sometimes needed to rule out heart, lung, or mediastinal diseases or other possible causes of the symptoms often seen with LP. Some vets may also recommend running a thyroid profile since LP can be a symptom or complication of hypothyroidism.