Diagnosis of tumefactive MS is commonly carried out using magnetic resonance imaging (MRI) and proton MR spectroscopy (H-MRS). Diagnosis is difficult as tumefactive MS may mimic the clinical and MRI characteristics of a glioma or a cerebral abscess. However, as compared to tumors and abscesses, tumefactive lesions have an open-ring enhancement as opposed to a complete ring enhancement. Even with this information, multiple imaging technologies have to be used together with biochemical tests for accurate diagnosis of tumefactive MS.

Tumefactive demyelination is distinguished from tumor by the presence of multiple lesions, absence of cortical involvement, and decrease in lesion size or detection of new lesions on serial imaging

MRI diagnosis is based on lesions that are disseminated in time and space, meaning that there are multiple episodes and consisting of more than one area. There are two kinds of MRI used in the diagnosis of tumefactive MS, T1-weighted imaging and T2-weighted imaging. Using T1-weighted imaging, the lesions are displayed with low signal intensity, meaning that the lesions appear darker than the rest of the brain. Using T2-weighted imaging, the lesions appear with high signal intensity, meaning that the lesions appear white and brighter than the rest of the brain. When T1-weighted imaging is contrast-enhanced through the addition of gadolinium, the open ring enhancement can be viewed as a white ring around the lesion. A more specific MRI, Fluid attenuation inversion recovery (FLAIR) MRI show the signal intensity of the brain. Subjects with tumefactive multiple sclerosis may see a reduction of diffusion of the white matter in the affected area of the brain.

The features of the MRI and the characteristics of the lesion can be correlated when a biopsy has been taken, providing a way to standarize the future MRI diagnosis

Balo concentric sclerosis lesions can be distinguished from normal lesions on MRI showing alternative hypotense and hypertense layers

Balo concentric lesions can be viewed using the myelin water imaging techniques. This is a special MRI sequence that shows the myelin's percentage of water content.

Pattern III lesions, including Balo lesions, have a specific initiation pattern under MRI (MRILIP) consisting in showing Gadolinium enhancement before FLAIR MRI appearance.

Multiple sclerosis is typically diagnosed based on the presenting signs and symptoms, in combination with supporting medical imaging and laboratory testing. It can be difficult to confirm, especially early on, since the signs and symptoms may be similar to those of other medical problems. The McDonald criteria, which focus on clinical, laboratory, and radiologic evidence of lesions at different times and in different areas, is the most commonly used method of diagnosis with the Schumacher and Poser criteria being of mostly historical significance.

Clinical data alone may be sufficient for a diagnosis of MS if an individual has had separate episodes of neurological symptoms characteristic of the disease. In those who seek medical attention after only one attack, other testing is needed for the diagnosis. The most commonly used diagnostic tools are neuroimaging, analysis of cerebrospinal fluid and evoked potentials. Magnetic resonance imaging of the brain and spine may show areas of demyelination (lesions or plaques). Gadolinium can be administered intravenously as a contrast agent to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation. Testing of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation in the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on electrophoresis, which are inflammation markers found in 75–85% of people with MS. The nervous system in MS may respond less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined using visual- and sensory-evoked potentials.

While the above criteria allow for a non-invasive diagnosis, and even though some state that the only definitive proof is an autopsy or biopsy where lesions typical of MS are detected, currently, as of 2017, there is no single test (including biopsy) that can provide a definitive diagnosis of this disease

A report comparing 1H-magnetic resonance spectroscopy, magnetization transfer and diffusion tensor imaging with histopathology in a patient with Balo's concentric sclerosis, found that inflammation was traced by fractional anisotropy and increased lactate. In contrast, magnetization transfer ratio and the diffusion coefficient show a loss of tissue in the rings of the lesion.

Below are various methods/techniques used to diagnose demyelinating diseases.

- Exclusion of other conditions that have overlapping symptoms

- Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to visualize internal structures of the body in detail. MRI makes use of the property of nuclear magnetic resonance (NMR) to image nuclei of atoms inside the body. This method is reliable because MRIs assess changes in proton density. "Spots" can occur as a result of changes in brain water content.

- Evoked potential is an electrical potential recorded from the nervous system following the presentation of a stimulus as detected by electroencephalography (EEG), electromyography (EMG), or other electrophysiological recording method.

- Cerebrospinal fluid analysis (CSF) can be extremely beneficial in the diagnosis of central nervous system infections. A CSF culture examination may yield the microorganism that caused the infection.

- Quantitative proton magnetic resonance spectroscopy (MRS) is a non-invasive analytical technique that has been used to study metabolic changes in brain tumors, strokes, seizure disorders, Alzheimer's disease, depression and other diseases affecting the brain. It has also been used to study the metabolism of other organs such as muscles.

- Diagnostic criteria refers to a specific combination of signs, symptoms, and test results that the clinician uses in an attempt to determine the correct diagnosis.

- Fluid-attenuated inversion recovery (FLAIR) uses a pulse sequence to suppress cerebrospinal fluid and show lesions more clearly, and is used for example in multiple sclerosis evaluation.

The Poser criteria for diagnosis are:

- One or two roughly symmetrical large plaques. Plaques are greater than 2 cm diameter.

- No other lesions are present and there are no abnormalities of the peripheral nervous system.

- Results of adrenal function studies and serum very long chain fatty acids are normal.

- Pathological analysis is consistent with subacute or chronic myelinoclastic diffuse sclerosis.

Also inside standard MS different clinical courses can be separated.

AQP4-Ab-negative NMO presents problems for diagnosis. The behavior of the oligoclonal bands respect MS can help to establish a more accurate diagnosis. Oligoclonal bands in NMO are rare and they tend to disappear after the attacks, while in MS they are nearly always present and persistent.

It is important to notice for differential diagnosis that, though uncommon, it is possible to have longitudinal lesions in MS

Other problem for diagnosis is that AQP4ab in MOGab levels can be too low to be detected. Some additional biomarkers have been proposed.

Currently there is no single diagnosis test for MS that is 100% sensitive and specific. To have such a thing would require a standardised definition of the disease, which currently does not exist. The most commonly used definition, based in the McDonald criteria, focuses in the presence and distribution of the lesions, not in the underlying condition that produces them. Therefore, even twins with the same underlying condition can be classified different

While diagnostic criteria are not expected to change in the near future, work to develop biomarkers that help with diagnosis and prediction of disease progression is ongoing. New diagnostic methods that are being investigated include work with anti-myelin antibodies, and studies with serum and cerebrospinal fluid, but none of them has yielded reliably positive results.

At the current time, there are no laboratory investigations that can predict prognosis. Several promising approaches have been proposed including: interleukin-6, nitric oxide and nitric oxide synthase, osteopontin, and fetuin-A. Since disease progression is the result of degeneration of neurons, the roles of proteins showing loss of nerve tissue such as neurofilaments, tau, and N-acetylaspartate are under investigation. Other effects include looking for biomarkers that distinguish between those who will and will not respond to medications.

Improvement in neuroimaging techniques such as positron emission tomography (PET) or magnetic resonance imaging (MRI) carry a promise for better diagnosis and prognosis predictions, although the effect of such improvements in daily medical practice may take several decades. Regarding MRI, there are several techniques that have already shown some usefulness in research settings and could be introduced into clinical practice, such as double-inversion recovery sequences, magnetization transfer, diffusion tensor, and functional magnetic resonance imaging. These techniques are more specific for the disease than existing ones, but still lack some standardization of acquisition protocols and the creation of normative values. There are other techniques under development that include contrast agents capable of measuring levels of peripheral macrophages, inflammation, or neuronal dysfunction, and techniques that measure iron deposition that could serve to determine the role of this feature in MS, or that of cerebral perfusion. Similarly, new PET radiotracers might serve as markers of altered processes such as brain inflammation, cortical pathology, apoptosis, or remylienation. Antibiodies against the Kir4.1 potassium channel may be related to MS.

The Mayo Clinic proposed a revised set of criteria for diagnosis of Devic's disease in 2006. Those new guidelines require two absolute criteria plus at least two of three supportive criteria. In 2015 a new review was published by an international panel refining the previous clinical case definition but leaving the main criteria unmodified:

Absolute criteria:

1. Optic neuritis

2. Acute myelitis

Supportive criteria:

1. Brain MRI not meeting criteria for MS at disease onset

2. Spinal cord MRI with continuous T2-weighted signal abnormality extending over three or more vertebral segments, indicating a relatively large lesion in the spinal cord

3. NMO-IgG seropositive status (The NMO-IgG test checks the existence of antibodies against the aquaporin 4 antigen.)

The 1996 definition of the clinical courses of MS (phenotypes) was updated on 2013 by an international panel (International Advisory Committee on Clinical Trials).

While the main classification in 1996 was the recovery from the attacks (this clinical feature separates RR from progressive), in the updated revision the main classification is the activity.

MS courses in the new revision are divided into active and non-active, and CIS, when is active on MRI, becomes a kind of RRMS (this, of course, must be retrospectively diagnosed after the CDMS conversion)

Some reviews describe CIS as "the prodromal stage of MS".

The typical demyelinating plaques in Schilder's sclerosis are usually found bilaterally in the semioval center; both hemispheres are almost completely occupied by large, well defined lesions. Although plaques of this kind are largely prevalent in Schilder's sclerosis, smaller lesions can also be observed.

Demyelinating diseases can be divided in those affecting the central nervous system and those presents in the peripheral nervous system, presenting different demyelination conditions. They can also be divided by other criteria in inflammatory and non-inflammatory, according to the presence or lack of inflammation, and finally, a division can also be made depending on the underlying reason for demyelination in myelinoclastic (myelin is attacked by an external substance) and leukodystrophic (myelin degenerates without attacks)

A clinically isolated syndrome (CIS) is a clinical situation of an individual's first neurological episode, caused by inflammation or demyelination of nerve tissue. An episode may be monofocal, in which symptoms present at a single site in the central nervous system, or multifocal, in which multiple sites exhibit symptoms. CIS with enough paraclinical evidence can be considered as a clinical stage of Multiple Sclerosis (MS). It can also be retrospectively diagnosed as a kind of MS when more evidence is available.

Brain lesions associated with a clinically isolated syndrome may be indicative of several neurological diseases, like multiple sclerosis (MS) or Neuromyelitis optica. In order for such a diagnosis, multiple sites in the central nervous system must present lesions, typically over multiple episodes, and for which no other diagnosis is likely. A clinically definitive diagnosis of MS is made once an MRI detects lesions in the brain, consistent with those typical of MS. Other diagnostics include cerebrospinal fluid analysis and evoked response testing.

Currently it is considered that the best predictor of future development of clinical multiple sclerosis is the number of T2 lesions visualized by magnetic resonance imaging during the CIS. It is normal to evaluate diagnostic criteria against the "time to conversion to definite".

In 2001, the International Panel on the Diagnosis of Multiple Sclerosis issued the McDonald criteria, a revision of the previous diagnostic procedures to detect MS, known as the Poser criteria. "While maintaining the basic requirements of dissemination in time and space, the McDonald criteria provided specific guidelines for using findings on MRI and cerebrospinal fluid analysis to provide evidence of the second attack in those individuals who have had a single demyelinating episode and thereby confirm the diagnosis more quickly." Further revisions were issued in 2005.

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 a recent analysis (Susac et al., 2003), MRI images from 27 patients fulfilling the diagnostic criteria of Susac's syndrome were reviewed. Multifocal supratentorial lesions were present in all patients. Most lesions were small (3 to 7 mm), though some were larger than 7 mm. All 27 patients had corpus callosum lesions. These all had a punched-out appearance on follow up MRI. Though most commonly involving white matter, many patients also had lesions in deep grey matter structures, as well as leptomeningeal enhancement. Multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) can mimic the MRI changes seen in patients with Susac's syndrome. However, the callosal lesions in Susac's syndrome are centrally located. In comparison, patients with MS and ADEM typically have lesions involving the undersurface of the corpus callosum. Deep gray matter involvement commonly occurs in ADEM but is very rare in MS. Leptomeningeal involvement is not typical of either MS or ADEM. What this means is that if 10 lesions are found in the brain of an MS patient, a lesion may be found in the corpus callosum. If you have 10 lesions in a Susac patient, more than half will be in the corpus callosum.

A concern about this illness is that it mimics multiple sclerosis when looking at the vision loss and brain lesions. If close attention is not paid to the retina of a patient with vision loss and brain lesions, their symptoms may be mistaken for MS instead of Susac's syndrome. This may account for the low prevalence of the illness. There is also a pathological similarity between the endotheliopathy in Susac's syndrome with that seen in juvenile dermatomyositis.

Socioeconomic correlates of health have been well established in the study of heart disease, lung cancer, and diabetes. Many of the explanations for the increased incidence of these conditions in people with lower socioeconomic status (SES) suggest they are the result of poor diet, low levels of exercise, dangerous jobs (exposure to toxins etc.) and increased levels of smoking and alcohol intake in socially deprived populations. Hesdorffer et al. found that low SES, indexed by poor education and lack of home ownership, was a risk factor for epilepsy in adults, but not in children in a population study. Low socioeconomic status may have a cumulative effect for the risk of developing epilepsy over a lifetime.

Although hippocampal sclerosis is relatively commonly found among elderly people (≈10% of individuals over the age of 85 years), association between this disease and ageing remains unknown.

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.

PML is diagnosed in a patient with a progressive course of the disease, finding JC virus DNA in spinal fluid together with consistent white matter lesions on brain magnetic resonance imaging (MRI); alternatively, a brain biopsy is diagnostic when the typical histopathology of demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei are present, coupled with techniques showing the presence of JC virus.

Characteristic evidence of PML on brain CT scan images are multifocal, non-contrast enhancing hypodense lesions without mass effect, but MRI is far more sensitive than CT. The most common area of involvement is the cortical white matter of frontal and parieto- occipital lobes, but lesions may occur anywhere in the brain, like the basal ganglia, external capsule, and posterior cranial fossa structures like the brainstem and cerebellum.

Although typically multifocal, natalizumab-associated PML is often monofocal, predominantly in the frontal lobe.

It took its name from Otto Marburg. It can be diagnosed "in vivo" with an MRI scan.

If Marburg disease occurs in the form of a single large lesion, it can be radiologically indistinguishable from a brain tumor or abscess. It is usually lethal, but it has been found to be responsive to Mitoxantrone and Alemtuzumab, and it has also been responsive to autologous stem cell transplantation. Recent evidence shows that Marburg's presents a heterogeneous response to medication, as does standard MS.

One third up to one half of people with PML die in the first few months following diagnosis, depending on the severity of their underlying disease. Survivors can be left with variable degrees of neurological disability.

Early and aggressive treatment is important to prevent irreversible neurological damage, hearing loss, or vision loss. Medications used include immunosuppressive agents and corticosteroids such a prednisone, or intravenous immunoglobulins (IVIG). Other drugs that have been used are mycophenolate mofetil (Cellcept), azathioprine (Imuran), cyclophosphamide, rituximab, and anti-TNF therapies.

Hearing aids or cochlear implants may be necessary in the event of hearing loss.