MS Diagnostics

MS diagnostics has undergone a major evolution over the last 100 years. From mere definition of clinical symptoms, through emergence of electrophysiological and biochemical methods to triumphant confirmation of a diagnosis using the magnetic resonance.

It showed even small inflammatory focuses and the dynamics of the disease, during which 3-10 times more focuses that can be seen by means of MRI are formed than the number of clinical attacks that occur. The old clinicians were right in saying that the disease never sleeps.

ClinicalLY Isolated Syndrome – CIS

Most patients will seek out a physician in a stage that is referred to as a clinically isolated syndrome (CIS). These are the first neurological problems, which arouse suspicion of a possibility of development of clinically definite multiple sclerosis (CDMS). This most often involves an inflammation of the optic nerve or symptoms from the area of brain stem, cerebellum, spinal cord or cerebral hemispheres. We can evaluate neurological manifestations such as CIS only after carefully carrying out laboratory and imaging examinations and after excluding other diseases of the central nervous system.

Since scientific data bring many pieces of evidence that it is necessary to start treating the disease as soon as possible, the diagnostic criteria were also being adapted to this trend. The past criteria from the year 2005 permitted not to wait for the second attack but it was possible to document the activity of the disease and dissemination over time by finding a new focus using MRI. The latest criteria make it possible to diagnose MS in many patients as early as when the first symptoms occur, which we call a clinically isolated syndrome (CIS). 

The currently valid diagnostic criteria are the third version of what is known as McDonald’s criteria (the original ones were defined in 2001; then they were revised in 2005; and the latest revision was in 2010), which was the first to include the magnetic resonance findings in its algorithm. The evolution of these criteria reflects the evolution of the auxiliary examination methods and the collection of data from extensive sets of patients.

The criteria are based on the clinical picture of the disease, referred to as the typical symptoms. They require that at least one attack should be documented by an objective finding on a magnetic resonanceThe basic diagnostic requirement is a proof of dissemination of a process in time and space.

The importance of early diagnosis and treatment of MS highlights the challenge of experts "Brain health - Time Matters in MS" adopted at ECTRIMS Congress 2015 in Barcelona.

Diagnosing MS always requires carrying out careful assessment of medical history, clinical examination, course of the disease and symptoms, carrying out the necessary auxiliary examinations and carefully ruling out other diseases.

Magnetic Resonance (MR)

The magnetic resonance method used in routine clinical practice since the 1990s allows for showing images of even small focuses of inflammation. It is an examination which does not burden the patient with X-rays but people who have metals in their bodies must not undergo this examination. At present, the joint replacements or clips used in surgery are made of non-magnetic materials. However, this information is always requested before the examination. An absolution counter-indication of the examination is a cardiostimulator and a hearing implant. 

The essence of the examination is the influence of a strong magnetic field on some parts of atoms in human organism. Orientation of these atom parts is different in individual tissues and this allows their differentiation, which is carried out by computer processing. This examination is able to display the places of changed tissue or abnormally permeable blood-brain barriers, which characterise inflammatory focuses, with the precision of one millimetre. In some cases, it is possible to identify whether disintegration products of myelin or focuses where nerve fibres have already been scarred and lost are found in such affected tissue.

On a magnetic resonance image, it is possible to observe the focuses of a signal with high intensity (that is, bright white ones on images referred to as T2-weighted images), particularly around cerebral ventricles, less often in the white matter of the brain stem and the cerebellum. Their size ranges from one millimetre to several centimetres. Above the ceilings of the lateral ventricles, we can often see the chains of such focuses like a string of beads.

In patients older than 45 years, it is often possible to find similar focuses not only in the typical areas for MS (the white matter of the brain and the spinal cord, located particularly around cerebral ventricles) but also in the grey brain matter. It is then difficult to differentiate them from small cerebral blood vessels affected by atherosclerotic changes. Inflammatory disease of blood vessels, vasculitis, can also have a very similar picture on MR like MS.

Course of Examination

The patient stays in the tunnel of the examination apparatus for several minutes and it can be unbearable for patients suffering from claustrophobia (fear of enclosed spaces). It is necessary that the patient tells about these problems to their physician in time.

During the examination, noise is heard in the examination tunnel. Patients are informed of this in time because their cooperation and ability to undergo the examination without moving is a prerequisite for its reliable assessment by the attending physician. The examination is not routinely carried out during pregnancy because so far there is not enough information on the influence of a strong magnetic field on a developing foetus.

Examination of Cerebrospinal Fluid

Examination of cerebrospinal fluid used to be a mandatory part of the diagnostic process. Due to massive dissemination of MRI apparatuses, it started to be omitted in some countries (particularly the USA). However, in Europe, mainly in Scandinavia and the German-speaking countries, and in our country, it is still a part of the golden standard of MS diagnostics.

The information obtained from a detailed examination of cerebrospinal fluid is irreplaceable for the attending physician and cannot be obtained in any other way. In this way, it is possible obtain information on the presence of inflammatory cells, which are washed from the focuses of inflammation into cerebrospinal fluid pathways, if these focuses are situated in their vicinity, on production of antibodies produced in the environment of the nervous system, and on production of other proteins, which influence the activity of the inflammation in a positive or negative way.

During the period of activity of the disease (an attack), cells are proliferated. At present, some laboratory instruments make it possible to examine the activation signs on these cells (particularly lymphocytes). These activation signs are molecules, which the cells move to the surface of membranes in order to be better able to participate in the inflammation. Microscopic examination of these cells may reveal cells producing antibodies (plasmatic cells) or cells, which clean up the disintegrated envelopes of nerve pathways, the disintegrated myelin (known as macrophages).

The antibodies participating in the destruction of the myelin envelope of nerve fibres are arranged in special patterns in the process of division in an electric field (electrophoresis). We call these patterns oligoclonal bands and they can be found in more than 95 percent of patients with MS. They represent a significant support of MS diagnosis because they are not found in the serum of these patients and are thus the evidence of production of antibodies directly in the area of the nervous system. (These bands can also occur with other chronic inflammations of the CNS, therefore their identification in itself is not sufficient to diagnose MS; however, with other inflammations, they are mostly situated in a different part of the examined pH spectrum.)

Course of Examination

Before lumbar puncture, it must be clear that the brain swelling or tumour or haemorrhaging is not present in the patient (this could cause shift of the brain tissue into the large opening in the occipital bone); this is why it is necessary to examine eye background or to use an imaging examination method (MR or CT).

Lumbar puncture can be carried out without hospitalisation, using an atraumatic needle, which has a pencil-point and an opening on the side for collection of cerebrospinal fluid. Therefore, it does not traumatise the cerebrospinal membrane and does not create an opening, through which the fluid can drop into hypodermis after the procedure and cause underpressure or reduced pressure in the cerebrospinal fluid system. Such underpressure leads to what is referred to as “post-puncture” problems: headaches in vertical position (the headaches disappear when the person lies down); nausea or vomiting; vertigo.

If the syndrome of post-puncture problems occurs, it can be easily remove by means of what is referred to as “blood patch”, which means that an anaesthesiologist collects a little amount of blood from a vein and applies it at the place of the opening in the cerebrospinal membrane. With this, the opening is sealed with the fibrin from the blood and complete relief comes within 1 – 2 hours.

Mostly around 10 ml of cerebrospinal fluid is collected; the quantity of protein, albumin, IgG, the number and quality of cells are routinely examined and if there is suspicion of MS, particularly the presence of oligoclonal bands is examined using isoelectric focusing.

It is not necessary to be afraid of lumbar puncture.

It is important to know that the material collected is cerebrospinal fluid and not spinal cord and that after 10 ml are taken, the fluid will be replenished within several minutes because around half a litre is produced over a day and there are only 150 ml of this fluid around the spinal cord and in cerebral ventricles. This means that it is regenerated three times a day. Caffeine increases its production; therefore, it is recommended that the patient drinks caffeine beverages after the procedure. It is advisable that the patient spends approximately 20 minutes lying on their stomach after the procedure; if the patient does not get dizzy after sitting up, they can leave the bed. The patient can shower the point of the puncture in the evening. On that day, the patient should not perform any physically straining activity or stay in the sun with their head unprotected.

Further Examinations in the Case of Differential Diagnostics

Sometimes, the finding is not quite typical, especially if only a single focus is present on the MR image or if the finding in cerebrospinal fluid is inconclusive (the same number of bands in the cerebrospinal fluid as in the serum; other cells than lymphocytes and monocytes) and it is necessary to search for a broader spectrum of diseases.

One percent of demyelinations is caused by a disease very similar to MS, which we long believed to occur only in Asia: neuromyelitis optica, the Devic’s disease. It affects particularly the optic nerve and the spinal cord; on MR image, it does not show a finding typical of MS; it mostly does not present oligoclonal bands in cerebrospinal fluid but it is possible to find antibodies against a water channel on astrocytes, aquaporin 4, in the blood. We have been able to examine these antibodies in the Czech Republic since 2007. It is important to distinguish this disease from MS because the long-term treatment significantly differs.

Other clinical symptoms are typical of other autoimmune inflammatory diseases (particularly rheumatic diseases – vasculitis): recurring miscarriages, recurring relapsing meningitides, epileptic seizures, thrombosis, ulcers in mouth and on genitals, headaches, psychiatric symptoms, involuntary movements, dystonia, etc.

Another group of diseases are hereditary metabolism disorders and degenerative diseases (particularly spinocerebellar ataxia, which may present a completely identical clinical finding like MS). Metabolic screening and genetic examination thus may be the next step to clarify the diagnosis.

MS can also occur in middle age. In that case, particularly vascular diseases of the brain come into consideration, which can have a similar finding on MR image. However, an examination of cerebrospinal fluid is of a completely fundamental importance in this case because oligoclonal bands are not present in vascular diseases.

Sometimes, even additional auxiliary examinations fail to clarify the diagnosis and the only option is to monitor the patient over time and to repeat some of the examinations.

More: Havrdová E. et al., Roztroušená skleróza v praxi, Galén, Praha 2015.»