notes by dr Claudio Italiano
To understand what demyelinating diseases consist of, it is first necessary to
know how a nerve is made. It is like a kind of electrical wire that conducts a
signal. It certainly does not have a copper soul, but to refer to the example of
the electric cable, we will say that it has an outer part, the sheath, in our
case myelinated, and an interior represented by the actual nerve fiber,
essentially constituted by the extension of the body of the nerve cell itself.
As happens with an electric wire that if the plastic sheath deteriorates, it starts to spark and an electric circuit goes into blackout, due to a short circuit, so if the nerve deteriorates in its myelin sheath, the nerve transmission deteriorates to stop altogether. Now we must also know that the nerves conduct electrical signals in the periphery, towards the muscles and allow movement, and, conversely, from the periphery to the brain, they conduct electrical signals of sense, which inform the brain about sensations, eg. the touch, the warmth, the posture of a limb and so on. The myelin sheath envelopes many nerve fibers within the central and peripheral nervous system; it has the function of accelerating the axonal transmission of nerve impulses. Diseases affecting myelin cause an interruption of nerve transmission; the symptoms may reflect an alteration in any part of the nervous system. Myelin is produced by some specialized cells, the oligodendrocytes, which produce it.
In the central nervous system, it differs, due to chemical and immunological characteristics, from that produced peripherally by Schwann cells. The myelin of the central nervous system consists of parallel layers of molecular lipids, superimposed to layers of hydrophilic proteins and has the function of protecting and covering the axons of the nerve cell. We had mentioned synapses and axons in the chapter on cognitive disturbance. Here, to make ourselves understood, with an apology for the neurologist colleagues who read us, we will say that myelin is like a sort of coating of an electric wire, essentially as the plasticized sheath of the electric wires of the circuits, with interruptions called "Nodes of Ranvier ", where ions and solutes pass and the nerve exchanges with the extracellular environment. Thus, to use a syllogism, in the event that it is destroyed, it will have, so to speak, a disturbance of the conduction of the signal, which in our case is a nervous signal that travels, in fact, in the axon of the nerve cell. The main share of the constituents of myelin is the share of lipids that reaches 75%, against the remaining protein quota. Myelin turnover continues throughout life, even if it decreases in the elderly.
They are divided into central, that is of the brain, and peripheral, that is,
peripheral nerves
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Paralisi in periferia
The areas most frequently affected in the central nervous system are the brain,
spinal cord and optic nerves. Demyelination is often secondary to infectious,
ischemic, metabolic, hereditary or toxin diseases, diabetes (eg, alcohol,
ethambutol). In primitive demyelinating diseases the cause is unknown, however
the involvement of an autoimmune mechanism is suspected, since the disease
sometimes follows a viral infection or a vaccination against a virus.
Demyelination tends to be segmental or patchy, affecting multiple areas,
simultaneously or in sequence. Often a remyelination occurs, with repair,
regeneration and complete recovery of the neuronal function. However, extensive
loss of myelin is usually followed by axon degeneration and often of the cell
body; both can be irreversible.
- Guillain-Barré syndrome,
- chronic demyelinating inflammatory polyneuropathy
- polyneuropathies tend to affect the peripheral nerves above all, while others
mainly affect the central nervous system (Pathologies that can cause
demyelination in the central nervous system).
The hypothesis of a demyelinating disease must be suspected in every patient
with neurological deficits that are not otherwise explainable. Primitive
demyelinating diseases should be suspected in the presence of:
-
Diffuse or multifocal deficiency
-
Sudden or subacute onset, especially in young adults
-
Onset within a few weeks of an infection or vaccination
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Symptoms with relapsing-remitting trend
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Indicative symptoms of a specific demyelinating disease (eg, unexplained optic
neuritis or internuclear ophthalmoplegia indicative of multiple sclerosis)
ALS is almost always a sporadic disease, with incidence of 1-3 cases per 100,000
individuals per year ie that appears absolutely random, only in 10% of cases we
recognize a genetic cause. It is a degenerative and progressive disease of the
nervous system that affects the so-called motion neurons, ie the cells of the
central nervous system, both at the encephalic level, called central motor
neurons or 1° motoneuron and at the level of the spinal cord and encephalic
trunk, or peripheral motor neurons or 2° motoneurone, at the level of the
encephalic trunk and the spinal cord. Cells degenerate and die but the causes
are still unknown. An important step towards an answer to the question occurred
in 1993, when some scientists discovered that mutations in the gene producing
superoxide dismutase Cu / Zn (also known as the SOD1 enzyme) were associated
with some cases of familial ALS (~ 20%). This enzyme has an antioxidant function
as it reduces the level of superoxide ion (O2-) a free toxic radical produced
during cellular oxidative metabolism capable of altering proteins, membranes and
DNA itself. Now, because the motoneurons are cells that transmit nerve signals
to the muscles for movement and, ultimately, for their good functioning and
trophism (hence the name "amiotrophic", it derives a course of the devastating
pathology, with outcome lethal, over 2-5 years, because the patient, little by
little, remains imprisoned with the lucid mind in a body that does not respond
to his commands and even to simple functions, such as respiratory action. they
are spared: bladder and intestinal function, sexual functions, sight and
heart.Thus, the term "lateral" comes from the fact that the lateral portions of
the spinal cord are affected.The etiopathogenetic hypotheses seem related to the
release of glutamate, which is an exciting neurotransmitter substance that would
cause oxidative toxic excitability, in the football world of 30,000 players, as
many as 51 were affected.
Multiple sclerosis is a disease of unknown etiology defined by symptoms and signs, with a typical temporal course that is characterized by multiple areas of inflammation, demyelination and axonal damage at the encephalic level.
A variety of growth factors are being explored as therapeutic agents relevant to the axonal and oligodendroglial deficits that occur as a result of demyelinating lesions such as are evident in Multiple Sclerosis (MS). Five proteins that are present in the lesion site impact oligodendrocyte regeneration. There is an approaches that are being exploited to manipulate the lesion environment affiliated with multiple neurodegenerative diseases and suggests that the utility of these approaches can extend to demyelination. Challenges are to further understand the roles of specific growth factors on a cellular and tissue level. Emerging technologies can then be employed to optimize the use of growth factors to ameliorate the deficits associated with demyelinating degenerative diseases.