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The Romanian Journal of Child and Adolescent Neurology and Psychiatry

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DEMYELINATING DISEASES OF THE CENTRAL NERVOUS SYSTEM &NDASH; CNS:CLASSIFICATION AND ELEMENTS OF AETIOPATHOGENESIS


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Se veral aetiopathogenic mechanisms and the classifi cation of demyelinating diseases of the CNS are presented, according to the currentliterature. Demyelinating diseases are caused by primary damage of myelin at the CNS level and are the result of an immune mediated infl ammatoryprocess, of genetic metabolic disorders of myelin metabolism, or of a primary demyelinating process due to a hypoxic-ischemic or toxic brain injury. Th emain clinical forms of acute disseminated encephalomyelitis are characterized, according to the mechanism of production, emphasizing the importance oftheir early recognition for the establishment of specifi c treatment with the time-limited evolution and improvement of the quality of life in the patientsdiagnosed with this disease.



 

In the group of the demyelinating diseases there are a series of diseases whose characteristic morphopathological feature is the damage and loss of myelin from the CNS. According to current literature, demyelinating diseases are described according to the aetiopathogenic mechanisms with primary involvement of the CNS.

The concept of primary demyelination involves the destruction of myelin, oligodentrocytes and Schwann cells with the preservation of other CNS components.

Axon damage is common in demyelinating lesions and correlates with permanent functional deficits.

CNS demyelinating diseases are the consequence of:

• an imune mediated inflamatory process followed by the disturbance of the normal development of myelin (demyelinating or myelinoclastic diseases);

• metabolic and genetic disorders in the myelin methabolism with the formation of abnormal myelin (dysmyelinating diseases);

• a process of primary demyelination aş a result of a hypoxic – ischemic or toxic cerebral lesion.

Table 1 presents the classification of myelin disorders in the CNS according to the mechanism that produces them [1].

Acute disseminated encephalomyelitis is the most common demyelinating disease in the child under 12 years of age, while multiple sclerosis is most common in adolescents and adults.

It is difficult to distinguish the acute disseminated encephalitis (ADE) from the first episode of Multiple Sclerosis (MS) For the MS diagnosis, a second, distinct episode is necessary after one month from the first appearance of ADE.

According to J. Menkes [1], however, this hypothesis is controversial because the second episode might be an ADE relapse and not the first episode of MS. This distinction might be made only in the prepubertal period.

Optic neuritis and the combination between optic neuritis and transverse myelitis (Devic disease) are frequently considered manifestations of ADE.

The pure transverse myelitis is considered a distinct nosologic entity due to a complex mechanism of production: autoimmune and postinfectious [1]

There is a semiological area of superposition between ADE and the Guillain Barré syndrome. It is difficult to classify the MS of the Marburg Type, the myelinoclastic MS (Schilder’s disease) and the Concentric Sclerosis (Baló’s disease).

In children under 2 years of age, who had a single severe demyelinating episode with oedema, the diagnosis should be MS or, more adequately, severe ADE.

The aetiopathological mechanism of these primary demyelinating diseases of the CNS (MS, ADE) is incompletely elucidated or even unknown (Devic’s Disease, Transverse Myelitis). Both MS and ADE are considered as autoimmune diseases, involving cellular and humoral responses directed, at least in part, towards myelin antigens;

The debut of MS does not have a clear aetiological relationship with a preceding infection; the clinical bursts of the disease are usually associated with the production of oligoclonal immunoglobulins that may be detected in the cerebrospinal fluid (CSF);

In many cases, MS is determined by an infectious disease and it is accompanied by increased concentrations of immunoglobulins in the CSF;

The normal profile of the immunoglobulins in the CSF is characteristic to the relapses in the ADE compared to MS, where the probability of abnormality


in immunoglobulins from CSF is higher than 94% in association with the recurrence in SM;

A small percentage of patients who presented typical bursts of ADE in their early childhood fulfil the clinical criteria for the diagnosis of multiple sclerosis in adolescence;

There are no specific diagnosis tests or disease biomarkers in order to differentiate ADE from SM in children.

It is difficult to differentiate ADE from other forms of inflammatory encephalitis.

The MRI sensitivity to demonstrate abnormalities in the development and maintenance of myelin has conceptually extended the disorders affecting myelin. Understanding the pathophysiology of leukodystrophies is evolving, and classifications of leucodistrophy continue to be arbitrary.

According to the Manual of Paediatric Neurology, Principles and Practice, 4th edition, by Kenneth F. Swaiman, the demyelinating diseases are presented as leukodystrophies and leukoencephalopathies [2].The concept of leukodystrophy has been changed considerably from the original definition, which was introduced in 1928 for the first time by Bielschowvki and Henneberg.

The term leukodystrophy should be restricted to genetic diseases affecting the development and maintenance of myelin and should exclude the acquired diseases affecting myelin, such as Multiple Sclerosis and other diseases associated with inflammatory lesions affecting myelin, the diseases due to certain toxic substances such as exposure to organic solvents.

Also, the term leukodystrophy is controversial because many genetic diseases affecting the white matter, and those diseases that are considered primary

leukodystrophies, may involve not only the white matter of CNS or not only the myelin. Even the primary leukodystrophy may involve more than only the white matter of the nervous system.

The term leukoencephalopathy is nore neuter and could be more precise. The leukoencephalopathies include genetic and acquired diseases which, selectively or predominantly involve the white matter of the

CNS irrespective of the basic pathophysiological or histological mechanism.

According to the pathological mechanism, the leukoencephalopathies may be coarsely divided into:

– dysmyelinating with abnormal formation of myelin and disorder in the myelination process,

– hypomielinating with decrease in the production of myelin,

– demyelinating with loss of myelin which was previously normal morphologically and functionally,

– spongiform with myelin division and formation of intramyelinic vacuoles,

– cystic with rarefaction of white matter and cystic degeneration.

Table 2 presents the leukoencephalopathies according to the pathogenic mechanism of production [3].

Aetiologicalclassificationof leukoencephalopathies:

According to their aetiology, leukoencephalopathies may be classified into the following

entities:

– Immune mediated leukoencephalopathies,

– Lipid metabolism disorders,

– Protein metabolism disorders,

– Aminoacid and organic acid metabolism disorders,

– Faulty energy metabolism,

– Other causes.

It is important to underline the fact that only an artificial classification into diseases with primary impact on the white matter from the spinal cord may

be formulated because the demyelinating diseases may also be the consequence of certain general metabolism disorders that affect the nervous system secondarily, such as: galactosemy, phenylketonuria, aciduria, Pompe disease and others (Kolodny, 1993) Table 3 presents the main aetiological forms of leukoencephalopathies [1].

CONCLUSIONS

The aetiologic diagnosis of primary demyelinating disease is not easy to support, considering the pathophysiological mechanisms involved in that condition. However, it is important, to recognize a primary demyelinating disease in order to institute a specific early treatment with timelimited evolution and improvement of the quality of life of these patients and of their families.

Corticotherapy, immunoglobulins and state-of-theart treatments (INTERFERON) have given a new meaning to the lives of patients diagnosed with demyelinating diseases at an early age.



Correspondence to:
magdalena.sandu@gmail.com