A diagnostic test for statin-associated auto-immune necrotizing myopathy will be available soon in order to differentiate between different types of myopathies during diagnosis. The presence of abnormal spontaneous electrical activity in the resting muscles indicates an irritable myopathy and is postulated to reflect the presence of an active necrotising myopathic process or unstable muscle membrane potential. However, this finding has poor sensitivity and specificity for predicting the presence of an inflammatory myopathy on biopsy. Further research into this spontaneous electrical activity will allow for a more accurate differential diagnosis between the different myopathies.

Currently a muscle biopsy remains a critical test, unless the diagnosis can be secured by genetic testing. Genetic testing is a less invasive test and if it can be improved upon that would be ideal. Molecular genetic testing is now available for many of the more common metabolic myopathies and muscular dystrophies. These tests are costly and are thus best used to confirm rather than screen for a diagnosis of a specific myopathy. Due to the cost of these tests, they are best used to confirm rather than screen for a diagnosis of a specific myopathy. It is the hope of researchers that as these testing methods improve in function, both costs and access will become more manageable

The increased study of muscle pathophysiology is of importance to researchers as it helps to better differentiate inflammatory versus non-inflammatory and to aim treatment as part of the differential diagnosis. Certainly classification schemes that better define the wide range of myopathies will help clinicians to gain a better understanding of how to think about these patients. Continued research efforts to help appreciate the pathophysiology will improve clinicians ability to administer the most appropriate therapy based on the particular variety of myopathy.

The mechanism for myopathy in individuals with low vitamin D is not completely understood. A decreased availability of 250HD leads to mishandling of cellular calcium transport to the sarcoplasmic reticulum and mitochondria, and is associated with reduced actomyosin content of myofibrils.

During vigorous ischemic exercise, skeletal muscle functions aerobically, generating lactate and ammonia a coproduct of muscle myoadenylate deaminase (AMPD) activity. The forearm ischemic exercise test takes advantage of this physiology and has been standardized to screen for disorders of glycogen metabolism and AMPD deficiency. Patients with a glycogen storage disease manifest a normal increase in ammonia but no change from baseline of lactate, whereas in those with AMPD deficiency, lactate levels increase but ammonia levels do not. If ischemic exercise testing gives an abnormal result, enzyme analysis must be performed on muscle to confirm the putative deficiency state because false-positive results can occur.

Elevated creatine kinase (CK) levels in the blood (at most ~10 times normal) are typical in sIBM but affected individuals can also present with normal CK levels. Electromyography (EMG) studies usually display abnormalities. Muscle biopsy may display several common findings including; inflammatory cells invading muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins. sIBM is a challenge to the pathologist and even with a biopsy, diagnosis can be ambiguous.

A diagnosis of inclusion body myositis was historically dependent on muscle biopsy results. Antibodies to cytoplasmic 5'-nucleotidase (cN1A; NT5C1A) have been strongly associated with the condition. In the clinical context of a classic history and positive antibodies, a muscle biopsy might be unnecessary.

IBM is often initially misdiagnosed as polymyositis. A course of prednisone is typically completed with no improvement and eventually sIBM is confirmed. sIBM weakness comes on over months or years and progresses steadily, whereas polymyositis has an onset of weeks or months. Other forms of muscular dystrophy (e.g. limb girdle) must be considered as well.

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.

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.

The diagnosis of the disease is mainly clinical (see diagnostic criteria). A laboratory workup is needed primarily to investigate for the presence of associated disorders (metabolic, autoimmune, and renal diseases).

- Every patient should have a fasting blood glucose and lipid profile, creatinine evaluation, and urinalysis for protein content at the first visit, after which he/she should have these tests on a regular basis.

- Although uncommon, lipid abnormalities can occur in the form of raised triglyceride levels and low high-density lipoprotein cholesterol levels.

- Patients usually have decreased serum C3 levels, normal levels of C1 and C4, and high levels of C3NeF (autoantibody), which may indicate the presence of renal involvement.

- Antinuclear antibodies (ANA) and antidouble-stranded deoxyribonucleic acid (DNA) antibodies have reportedly been observed in some patients with acquired partial lipodystrophy.

- A genetic workup should be performed if the familial form of lipodystrophy is suggested.

Laboratory work for associated diseases includes:

- Metabolic disease - fasting glucose, glucose tolerance test, lipid profile, and fasting insulin to characterize the insulin resistance state; free testosterone (in women) to look for polycystic ovary syndrome.

- Autoimmune disease - ANA, antidouble-stranded DNA, rheumatoid factor, thyroid antibodies, C3, and C3NeF.

As a confirmatory test, whole-body MRI usually clearly demonstrates the extent of lipodystrophy. MRI is not recommended on a routine basis.

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.

Diagnosis can be made solely on the basis of history and physical examination in people who present with only facial asymmetry. For those who report neurological symptoms such as migraine or seizures, MRI scan of the brain is the imaging modality of choice. A diagnostic lumbar puncture and serum test for autoantibodies may also be indicated in people who present with a seizure disorder of recent onset.

A review published in 2004, which was based on 35 patients seen by the respective authors over 8 years and also a literature review of 220 cases of acquired partial lipodystrophy (APL), proposed an essential diagnostic criterion. Based on the review and the authors experience, they proposed that APL presents as a gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the "cephalocaudal" sequence, sparing the lower extremities. The median age of the onset of lipodystrophy was seven years. Several autoimmune diseases, in particular systemic lupus erythematosus and dermatomyositis, were associated with APL. The prevalence rates of diabetes mellitus and impaired glucose tolerance were 6.7% and 8.9%, respectively. Around 83% of APL patients had low complement 3 (C3) levels and the presence of polyclonal immunoglobulin C3 nephritic factor. About 22% of patients developed membranoproliferative glomerulonephritis (MPGN) after a median of about 8 years following the onset of lipodystrophy. Compared with patients without renal disease, those with MPGN had earlier age of onset of lipodystrophy (12.6 ± 10.3 yr vs 7.7 ± 4.4 yr, respectively; p < 0.001) and a higher prevalence of C3 hypocomplementemia (78% vs 95%, respectively; p = 0.02).

The adipose stores of the gluteal regions and lower extremities (including soles) tend to be either preserved or increased, particularly among women. Variable fat loss of the palms, but no loss of intramarrow or retro-orbital fat, has been demonstrated.

Neurotoxin may act on the neuromuscular junction either post synaptically or presynaptically as there are several different forms of toxins that the NMJ is sensitive to.(reference 14) Common mechanisms of action include blockage of acetylcholine release at the synapse thus causing the NMJ to become abnormal in function.(reference 12)

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.

Myasthenia gravis is the most common neuromuscular disease affecting function of the end plate in patients. It is present in 100 people out of 1,000,000 in the population, and its onset is usually in either younger or older individuals.(reference 14)

Acquired myasthenia gravis is the most common neuromuscular junction disease.(reference 7) Important observations were made by Patrick and Lindstrom in 1973 when they found that antibodies attacking the acetylcholine receptors were present in around 85% of cases of myasthenia gravis.(reference renamed form 13)(reference 36) The remaining diseases were also a result of antibody attacks on vital proteins, but instead of the acetylcholine receptor, the culprits were MuSK, a muscle-specific serum kinase, and lipoprotein receptor-related protein.(reference 36) So these mechanisms describe myasthenia gravis that is acquired, and not congenital, affecting these vital proteins by an immunological response against self-antigens. The cases not caused by antibodies against the acetylcholine receptors became by convention called seronegative myasthenia gravis.(reference 37) The term seronegative came about because scientists would be testing for acetylcholine receptor antibodies in patients that had myasthenia gravis resulting in negative tests in the serum. This does not imply that there are no antibodies present, but this terminology only became present because scientists were testing for the wrong antigen.(reference 36)(reference 38)

Neonatal myasthenia gravis is a very rare condition in which a mother with myasthenia gravis passes down her antibodies to her infant through the placenta, causing the it to be born with antibodies that will attach self-antigens.(reference 12)

Drug-induced myasthenia gravis is also a very rare condition in which pharmacological drugs cause a blockade or disruption of the NMJ machinery.(reference 12) Robert W. Barrons summarizes the possible causes of drug-induced myasthenia gravis: "Prednisone was most commonly implicated as aggravating myasthenia gravis, and D-penicillamine was most commonly associated with myasthenic syndrome. The greatest frequency of drug-induced neuromuscular blockade was seen with aminoglycoside-induced postoperative respiratory depression. However, drugs most likely to impact myasthenic patients negatively are those used in the treatment of the disease. These include overuse of anticholinesterase drugs, high-dose prednisone, and anesthesia and neuromuscular blockers for thymectomy."(reference 39)

Among the methods of diagnosing tropical spastic paraparesis are MRI (magnetic resonance imaging) and lumbar puncture (which may show lymphocytosis).

The usual initial investigations include chest X ray, electrocardiogram and echocardiography. Typical findings are those of an enlarged heart with non specific conduction defects. Biochemical investigations include serum creatine kinase (typically increased 10 fold) with lesser elevations of the serum aldolase, aspartate transaminase, alanine transaminase and lactic dehydrogenase. Diagnosis is made by estimating the acid alpha glucosidase activity in either skin biopsy (fibroblasts), muscle biopsy (muscle cells) or in white blood cells. The choice of sample depends on the facilities available at the diagnostic laboratory.

In the late onset form, the findings on investigation are similar to those of the infantile form with the caveat that the creatinine kinases may be normal in some cases. The diagnosis is by estimation of the enzyme activity in a suitable sample.

On May 17, 2013 the Secretary's Discretionary Advisory Committee on Heritable Diseases in Newborns and Children (DACHDNC) approved a recommendation to the Secretary of Health and Human Services to add Pompe to the Recommended Uniform Screening Panel (RUSP). The HHS secretary must first approve the recommendation before the disease is formally added to the panel.

In terms of the differential diagnosis for polyneuropathy one must look at the following:

The prognosis for Tropical spastic paraparesis indicates some improvement in a percentage of cases due to immunosuppressive treatment. A higher percentage will eventually lose the ability to walk within a ten-year interval.

The diagnosis of polyneuropathies begins with a history and physical examination to ascertain the pattern of the disease process (such as-arms, legs, distal, proximal) if they fluctuate, and what deficits and pain are involved. If pain is a factor, determining where and how long the pain has been present is important, one also needs to know what disorders are present within the family and what diseases the person may have. Although diseases often are suggested by the physical examination and history alone, tests that may be employed include: electrodiagnostic testing, serum protein electrophoresis, nerve conduction studies, urinalysis, serum creatine kinase (CK) and antibody testing (nerve biopsy is sometimes done).

Other tests may be used, especially tests for specific disorders associated with polyneuropathies, quality measures have been developed to diagnose patients with distal symmetrical polyneuropathy (DSP).

Evaluation of a child with torticollis begins with history taking to determine circumstances surrounding birth and any possibility of trauma or associated symptoms. Physical examination reveals decreased rotation and bending to the side opposite from the affected muscle. Some say that congenital cases more often involve the right side, but there is not complete agreement about this in published studies. Evaluation should include a thorough neurologic examination, and the possibility of associated conditions such as developmental dysplasia of the hip and clubfoot should be examined. Radiographs of the cervical spine should be obtained to rule out obvious bony abnormality, and MRI should be considered if there is concern about structural problems or other conditions.

Ultrasonography is another diagnostic tool that has high frequency sound waves used to visualize the muscle tissue. A colour histogram can also be used to determine cross sectional area and thickness of the muscle.

Evaluation by an optometrist or an ophthalmologist should be considered in children to ensure that the torticollis is not caused by vision problems (IV cranial nerve , nystagmus-associated "null position," etc.).

Differential diagnosis for torticollis involves

- Cranial nerve IV palsy

- Spasmus nutans

- Sandifer syndrome

- Myasthenia gravis

Cervical dystonia appearing in adulthood has been believed to be idiopathic in nature, as specific imaging techniques most often find no specific cause.

Breathing difficulties can occur, resulting from neuromyotonic activity of the laryngeal muscles. Laryngeal spasm possibly resulting from neuromyotonia has been described previously, and this highlights that, in patients with unexplained laryngospasm, neuromytonia should be added to the list of differential diagnoses.

Studies have shown subtly decreased metabolism on positron emission tomography (PET) and single photon emission computed tomography (SPECT) in the left inferior frontal and left temporal lobes. and or basal ganglia hypermetabolism. Ancillary laboratory tests including MRI and brain biopsy have confirmed temporal lobe involvement. Cranial MRI shows increased signal in the hippocampus.

Cerebral spinal fluid (CSF) shows normal protein, glucose, white blood cell, and IgG index but there are weak oligoclonal bands, absent in the blood. Marked changes in circadian serum levels of neurohormones and increased levels of peripheral neurotransmitters were also observed. The absence of morphological alterations of the brain pathology, the suggestion of diffusion of IgG into the thalamus and striatum, more marked than in the cortex (consistent with effects on the thalamolimbic system) the oligoclonal bands in the CSF and the amelioration after PE all strongly support an antibody-mediated basis for the condition. Raised CSF IgG concentrations and oligoclonal bands have been reported in patients with psychosis. Anti-acetylcholine receptors (anti-AChR) antibodies have also been detected in patients with thymoma, but without clinical manifestations of myasthenia gravis. There have also been reports of non-paraneoplastic limbic encephalitis associated with raised serum VGKC suggesting that these antibodies may give rise to a spectrum of neurological disease presenting with symptoms arising peripherally, centrally, or both. Yet, in two cases, oligoclonal bands were absent in the CSF and serum, and CSF immunoglobulin profiles were unremarkable.

In the absence of a liver transplant, FAP is invariably fatal, usually within a decade. The disadvantage of liver transplantation is that approximately 10% of the subjects die from the procedure or complications resulting from the procedure, which is a form of gene therapy wherein the liver expressing wild type and mutant TTR is replaced by a liver only expressing wild type TTR. Moreover, transplanted patients must take immune suppressants (drugs) for the remainder of their life, which can lead to additional complications. In late 2011, the European Medicines Agency approved the transthyretin kinetic stabilizer Tafamidis or Vyndaqel discovered by Jeffery W. Kelly and developed by FoldRx pharmaceuticals (acquired by Pfizer in 2010) for the treatment of FAP based on clinical trial data. Tafamidis (20 mg once daily) slowed the progression of FAP over a 36-month period and importantly reversed the weight loss and muscle wasting associated with disease progression.

There are several types of immune-mediated neuropathies recognised. These include

- Chronic inflammatory demyelinating polyneuropathy (CIPD) with subtypes:

- Classical CIDP

- CIDP with diabetes

- CIDP/monoclonal gammopathy of undetermined significance

- Sensory CIDP

- Multifocal motor neuropathy

- Multifocal acquired demyelinating sensory and motor neuropathy (Lewis-Sumner syndrome)

- Multifocal acquired sensory and motor neuropathy

- Distal acquired demyelinating sensory neuropathy

- Guillain-Barre syndrome with subtypes:

- Acute inflammatory demyelinating polyradiculoneuropathy

- Acute motor axonal neuropathy

- Acute motor and sensory axonal neuropathy

- Acute pandysautonomia

- Miller Fisher syndrome

- IgM monoclonal gammopathies with subtypes:

- Waldenstrom's macroglobulinemia

- Mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome

- Myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome (POEMS)

For this reason a diagnosis of chronic inflammatory demyelinating polyneuropathy needs further investigations.

The diagnosis is usually provisionally made through a clinical neurological examination. Patients usually present with a history of weakness, numbness, tingling, pain and difficulty in walking. They may additionally present with fainting spells while standing up or burning pain in extremities. Some patients may have sudden onset of back pain or neck pain radiating down the extremities, usually diagnosed as radicular pain. These symptoms are usually progressive and may be intermittent.

Autonomic system dysfunction can occur; in such a case, the patient would complain of orthostatic dizziness, problems breathing, eye, bowel, bladder and cardiac problems. The patient may also present with a single cranial nerve or peripheral nerve dysfunction.

On examination the patients may have weakness, and loss of deep tendon reflexes (rarely increased or normal). There may be atrophy (shrinkage) of muscles, fasciculations (twitching) and loss of sensation. Patients may have multi-focal motor neuropathy, as they have no sensory loss.

Most experts consider the necessary duration of symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made.

Typical diagnostic tests include:

- Electrodiagnostics – electromyography (EMG) and nerve conduction study (NCS). In usual CIDP, the nerve conduction studies show demyelination. These findings include:

1. a reduction in nerve conduction velocities;

2. the presence of conduction block or abnormal temporal dispersion in at least one motor nerve;

3. prolonged distal latencies in at least two nerves;

4. absent F waves or prolonged minimum F wave latencies in at least two motor nerves. (In some case EMG/NCV can be normal).

- Serum test to exclude other autoimmune diseases.

- Lumbar puncture and serum test for anti-ganglioside antibodies. These antibodies are present in the branch of CIDP diseases comprised by anti-GM1, anti-GD1a, and anti-GQ1b.

- Sural nerve biopsy; biopsy is considered for those patients in whom the diagnosis is not completely clear, when other causes of neuropathy (e.g., hereditary, vasculitic) cannot be excluded, or when profound axonal involvement is observed on EMG.

- Ultrasound of the periferal nerves may show swelling of the affected nerves

- MRI can also be used in the diagnosic workup

In some cases electrophysiological studies fail to show any evidence of demyelination. Though conventional electrophysiological diagnostic criteria are not met, the patient may still respond to immunomodulatory treatments. In such cases, presence of clinical characteristics suggestive of CIDP are critical, justifying full investigations, including sural nerve biopsy.

Medical management may involve immunosuppressive drugs such as methotrexate, corticosteroids, cyclophosphamide, and azathioprine. No randomized controlled trials have yet been conducted to evaluate such treatments, so the benefits have not been clearly established.

The drug tafamidis has completed a phase II/III 18-month-long placebo controlled clinical trial

and these results in combination with an 18-month follow-on study demonstrated that Tafamidis or Vyndaqel slowed progression of FAP, particularly when administered to patients early in the course of FAP. This drug is now approved by the European Medicines Agency.

The US Food and Drug Administration's Peripheral and Central Nervous System Drugs Advisory Committee rejected the drug in June 2012, in a 13-4 vote. The committee stated that there was not enough evidence supporting efficacy of the drug, and requested additional clinical trials.

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.