Parkinson\'s disease

Epidemiology

Its prevalence in the Western countries increases with the age: it is from 1 to 2 per 1000 in the general population, it is rare before 50 years and rises from 6 to 8 per 1000 between 65 and 69 years; it passes from 26 to 35 per 1000 between 85 and 89 years. The usual age of beginning is around 60 years. The men are a little more often touched than the women (55 men for 45 women).

Physiopathology

Various structures of the sensorimotor Circuit of the Cerveau are implied in the disease, of which the central gray Noyaux. In particular, the Pars compacted black substance ( locus Niger ) is mainly destroyed (Apoptose of the Neuron S).

An important characteristic of this disease is the disordered state of the dopaminergique Système: there is a deficit of Dopamine (a Neurotransmetteur, molecule being used as chemical messenger between two neurons, synthesized in a termination axonale; the neuro-transmitter is released in the synaptic slit in answer to a nerve impulse) which does not exert any more a negative rétrocontrôle on the production of acetylcholine involving an imbalance dopamine - acetylcholine. Cerebral deteriorations are not limited only to the dopaminergique sphere and of many systems neuro-transmitters (serotoninergic or adrenergic) are also reached.

Causes

They are probably multifactorielles, including genetic predispositions and environmental Co-factors possibly acting as synergies. The exposure to heavy metals, with various pollutants of which with the pesticides was evoked.

The exposure to the pesticides would increase the disease risk of Parkinson of almost 70%: 5% of those which are exposed to the pesticides would be likely to develop the disease against 3% for the general population . This disease is indeed more frequent in rural environment than urban. In France, this disease does not appear however in the table of the Occupational disease in spite of some exceptions. In reaction, the CFE-CGC Federation of Chemistry said (in September 2006) to want to draw “the attention of the employers to the preventive attitudes to make adopt with paid in the event of handling of the pesticides”, because complete individual protections (boots, gloves, mask and combination) are still seldom used.

Diagnosis

One notes a progressive installation several elements:

muscular Hypertonicity Extrapyramidal E which one calls " plastique" in opposition to spastic hypertonicity. I.e. one with the feeling of " pipe of plomb" during the mobilization passivates of the member. This rigidity can yield by jolts (aspect of toothed wheel). The general attitude is in inflection (dorsal Kyphosis, semi-bent members) and gives an ahead leant aspect.
Tremor of rest of the ends in particular of the inch: " the patient counts his currency, rolls of the crumb of pain"
Akinésie i.e. scarcity of the movements and deterioration of the automatic movements such as the mimicry or the walk which are disturbed. It is the most important sign of the disease. The patient has an impassive face, the half-opened mouth, seldom blinking eyes. Walk slow with small steps, without swinging of the arms is sometimes intersected with stops. It can go until a dyskinesy (involuntary movements)

Other symptoms are frequently met: depression, falls, hypersalivation, inexhaustible oculo-palpebral reflex, a micrography (penmanship decreases in amplitude)… Cognitive disorders even a Démence can occur after several years of evolution.

The diagnosis of Parkinson's disease is usually clinical. It rests on the description of a akinesy associated with another symptom (rigidity, tremors of rest, turbid postural). There exists a certain number of neurologic affections presenting of the comparable signs but not answering the treatment. These affections are gathered under the term of parkinson's syndromes (progressive paralysis supranucléaire, atrophies multisystematized, etc…). In theory the diagnosis is established in an unquestionable way only by the histological study of the brain but the currently definite diagnostic criteria make it possible to make the diagnosis without too many difficulties. In certain cases, one can have recourse to the realization of a cerebral Scintigraphie (DATscan) which makes it possible to show the attack of striatum.

Differential diagnosis

Parkinson's syndrome

parkinson's Syndrome of with the Nerve sedative S (Butyrophénone S, Phénothiazine S) (the most frequent case)
Disease with body of Lewy precociously associated with a " démence" with visual hallucinations.

and exceptionally:

Disease of Wilson especially at a subject unusually young
progressive Paralysis supranucléaire (P.S.P.)
Atrophy multi systematized
certain intoxications with the MPTP (Drug-addiction)
Hydrocéphalie with normal pressure.

Of a tremor

There in particular exists more than one score of other causes of tremors, most frequent, the essential Tremblement, which is a tremor at the time of the movements (or in the maintenance of attitude), and not of rest, like the parkinsonian tremor. Only a diagnosis posed by a neurologist makes it possible to confirm the existence of a precise pathology.

Assumption of responsibility

Medicamentous treatment

Currently, no drug showed effectiveness on the progression of the disease: there does not exist curative treatment of the disease. The medicamentous treatment thus remains today still purely symptomatic (acting on the symptoms). To make up the cerebral dopaminergique deficit which characterizes the disease, a symptomatic treatment by the L-DOPA (precursory of the dopamine which is transformed into dopamine in the Cerveau) gives good performances, but loses of its effectiveness during time (typically after 3 to 6 years of treatment). it is all the same the treatment more used because most active. This drug will be transformed into dopamine and used by the organization. The transformation occurs in the central nervous system but also in all the organization by doped décarboxylase (enzyme present in all the body). In the periphery, that creates side effects like nauseas, vomiting, etc For this reason, this treatment is coupled with an inhibiter of the peripheral décarboxylase. That makes it possible to decrease the transformation in the periphery and thus to decrease the side effects while increasing by 10 the availability on the level of the central nervous system. The L-dopa has a half life (time with the end of which the molecule is with half eliminated from the organization) ranging between 1:30 and 3:00. The catches of the drug will thus be repeated and regular throughout the day in order to maintain a rate, and thus an effect, stable. The organization is less and less sensitive to the treatment with the years what involves a fluctuation of effect and dyskinésies (involuntary movements). The fluctuation appears initially. The symptoms can be important or attenuated. The catches of drugs can then be brought closer but the increased amount supports the dyskinésies.

The second main category of medicamentous treatment is the class of the dopaminergique agonists. Those can replace the L-dopa at the beginning of the disease, especially at the youngest patients, or be associated with the L-dopa at a stage more evolved/moved, thus making it possible to save the L-dopa and to preserve its longer-term effectiveness.

Other medicamentous treatments exist in particular to optimize the effectiveness of the L-dopa.

The treatment of the Parkinson's disease was the consensus object included in the recommendations of the High health official.

Dietetic measurements

A food rich in proteins can reduce the effectiveness of the levodopa. this can be circumvented by consuming proteins only the evening to push back the appearance of symptoms in a time slot where the patient needs less to control them. This medication is a good means of treating the symptoms, but does not constitute a treatment of the disease which has as a source the decline of the neurons producing the dopamine.

Physical exercises

The regular practice of exercises, (possibly within the framework of adapted Physical-activities) is essential to maintain mobility, flexibility, balance and to fight the side effects and symptoms.

Surgical treatment

A surgical treatment of the symptoms by establishment of electrode S of stimulation is available since 1998 in Europe, 2000 with the the United States. It was developed at the man by Alim-Louis Benabid with Grenoble in 1993, following studies led on the primate by Abdelhamid Benazzouz to Bordeaux. This technique of major cerebral stimulation tiny room strongly three driving symptoms of the disease. An electrode is established in the Noyau subthalamic, and a Neuro-stimulative sends electric impulses to it, which seems to restore the normal functioning of the system.

Genetic prospects

Another treatment with a future, genic therapy: It is able to produce neurons of a person reached by embryonic Clonage. These producing neurons of dopamine could then be established without risk of rejection; this was carried out successfully on mice. Other protocols calling upon other types of cells for example, with original cells neurales, are currently tested in the animal. They consist in modifying genetically the cells in vitro , in order to make them produce dopamine, then to graft them.

Lastly, another strategy, in the course of tests in the animal, aims to prevent the death of the neurons grace, in particular, with growth factors implied in their survival.

Anecdotes

Famous personalities carrying a Parkinson's disease :

External bonds

Parkinson' S Disease: symptoms, diagnosis, biochemistry, causes, treatments, history, prevalence, organizations, toxic causes, genetic causes
Pharmacology of the Parkinson's disease on the site of the university of Rennes

References

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