Parkinson's disease is a neurological disease affecting the central nervous system responsible for motor abnormalities of gradual evolution.
Its causes are not well known, but we know that certain substances, including pesticides, promote disease. The clinical picture is linked to a loss of neurons in the substantia nigra (substantia nigra) and a violation of the beams nigro-streaked. The onset is usually between 45 and 70 years. This is the second neuro-degenerative disease after Alzheimer's disease. He opposes Parkinsonian syndromes involving roughly the same clinical signs but are secondary to certain diseases or medications.
Its prevalence in Western countries increases with age: it is 1 to 2 per 1000 in the general population, it is rare before age 50 and is 6 to 8 for 1000 between 65 and 69 years, an increase from 26 to 35 per 1000 between 85 and 89 years. The usual age of onset is around 60 years. Men are more often affected than women (55 men to 45 women).
Different structures of sensory-motor circuit of the brain are involved in the disease, including the basal ganglia. In particular, the pars compacta of the substantia nigra (substantia nigra) is largely destroyed (apoptosis of neurons).
An important feature of this disease is a disorder of the dopaminergic system: there is a shortage of dopamine (a neurotransmitter, a substance used as a chemical messenger between two neurons, in a synthesized axonal termination, the neurotransmitter is released into the synaptic cleft in response to a nerve impulses), which no longer carries the negative feedback on the production of acetylcholine causing an imbalance dopamine - acetylcholine. The altered brain is not limited to the sphere dopaminergic systems and many neurotransmitters (serotonin or adrenergic) are also affected.
They are probably multifactorial, including genetic predisposition and environmental factors co-possibly acting in synergy. Exposure to heavy metals, to various pollutants including pesticides was raised.
Exposure to pesticides increase the risk of Parkinson's disease by nearly 70%: 5% of those exposed to pesticides risk of developing the disease compared with 3% for the general population. The disease is actually more prevalent in rural and urban areas.
In France, the disease does not, however, in the table of Professional Disease despite some exceptions. In response, the Federation CFE-CGC of Chemistry said (in September 2006) "would attract the attention of employers on attitudes to adopt preventive employees in the handling of pesticides," because the individual protections complete (boots , gloves, masks and combination) are still rarely used.
There has been a gradual installation of several elements:
* Hypertonia muscle extrapyramidal so-called "plastic" as opposed to the spastic hypertonia. That is to say it was the feeling of "lead pipe" at the mobilization passive member. This rigidity may transfer in fits (aspect of gears). The general attitude is flexural (Cyphose backbone, semi-bent members), and gives a leaning forward.
* Bam rest of the extremities including the thumb, "the patient account its currency, rolls of the bread crumb"
* Akinésie ie scarcity of movement and tampering with automatic movements such as walking or mimic who are disrupted. This is the most important sign of the disease. The patient has an impassive face, mouth ajar, rarely blinking of the eyes. Walking is slow in small steps, without swinging arm sometimes interspersed with stops. It can go up dyskinesia (involuntary movements)
Other symptoms are frequently encountered: depression, falls, hypersalivation, reflex-eye eyelid inexhaustible, a micrograph (calligraphy decreasing amplitude) ... The cognitive disorders or dementia may occur after several years of evolution.
The diagnosis of Parkinson's disease is usually clinical. It is based on the identification of a akinesia associated with another symptom (rigidity, tremor rest, postural disorder). There are a number of neurological diseases with signs similar but not responding to treatment. These conditions are grouped under the term Parkinsonian syndromes (progressive supranuclear paralysis, Multiple System Atrophy ...). In theory the diagnosis is established with certainty that by histological study of the brain but the currently defined diagnostic criteria used to make the diagnosis without much difficulty. In some cases, can be used to achieve a brain scan (DATscan), which allows the achievement of showing the striatum.
From parkinsonian syndrome
* Parkinson's Syndrome to neuroleptics (butyrophenones, phenothiazines) (the most common case)
* Disease with Lewy bodies précocément associated with a "insanity" with visual hallucinations.
* Wilson's disease especially in a subject unusually young
* Paralysis progressive supranuclear (P.S.P.)
* Atrophy multi-systematisée
* Certain poisoning MPTP (addiction)
* At normal pressure hydrocephalus.
There are more than twenty other causes of the quakes, including the most common, essential tremor, which is a tremor during movement (or in the maintenance of attitude), not rest, as parkinsonian tremor. Only a diagnosis by a neurologist to confirm the existence of a specific pathology.
Currently, no drug has demonstrated effectiveness on the progression of the disease: There is no cure for the disease.
Drug treatment still remains purely symptomatic (acting on the symptoms).
To offset the deficit dopaminergic brain that characterize the disease, symptomatic treatment by the L-DOPA (precursor of dopamine, which is converted into dopamine in the brain) is a success, but loses its effectiveness over time (typically after 3 to 6 years of treatment). It's just the treatment is more widely used because most active. This medicine will be transformed into dopamine and used by the body. The transformation occurs in the central nervous system but also throughout the body by dopa decarboxylase (enzyme present throughout the body). In the periphery, it creates side effects such as nausea, vomiting, and so on. For this reason, this treatment is coupled to a peripheral decarboxylase inhibitor. This reduces processing in the periphery and thus reduce side effects while increasing availability by 10 to the central nervous system. The L-dopa has a half life (time during which the molecule is half eliminated from the body) between 1:30 and 3 am. The catch of the drug and will be repeated regularly throughout the day in order to maintain a rate, and therefore a fact, stable. The agency is becoming less sensitive to treatment with the years leading to a fluctuation of effect and dyskinesia (involuntary movements). The fluctuation appears in the first place. Symptoms may be important or mitigated. Catches of drugs can be reconciled but fosters increased dose dyskinesia.
The second broad category of drug treatment is the class of dopamine agonists. They can replace L-dopa at the beginning of the disease, especially among the younger patients, or be associated with L-dopa in a more advanced stage, saving L-dopa and preserve its effectiveness in the longer term.
Other drug treatments exist especially for maximizing the effectiveness of L-dopa.
The treatment of Parkinson's disease has been a consensus reflected in the recommendations of the High Authority of Health.
A diet rich in protein can reduce the effectiveness of levodopa. This can be circumvented by not consuming proteins that evening to postpone the onset of symptoms in a time slot where the patient has less need to control them. This medication is a good way to treat the symptoms, but is not a treatment of the disease which has source for the decline in dopamine-producing neurons.
The practice exercises on a regular basis, (possibly through adapted physical activities) is essential to maintain mobility, flexibility, balance and to combat the effects and symptoms. In addition, the regular practice of a sport can increase the secretion of natural dopamine [ref. Required].
A surgical treatment of symptoms by implantation of electrodes stimulation has been available since 1998 in Europe, 2000 in the United States. It was developed in humans by Alim-Louis Benabid in Grenoble in 1993, following a study conducted on the primate by Abdelhamid Benazzouz in Bordeaux. This technique of deep brain stimulation significantly reduced the three motor symptoms of the disease. An electrode is implanted in the subthalamic nucleus, and a neuro-stimulator sends electrical impulses, which seems to restore the normal functioning of the system. Unfortunately, this treatment can now be applied to only about 10% of patients, because of the cumbersome nature of the operation and effectiveness criteria very strict.
A new treatment with electrical stimulation of the motor cortex is under study since 2004 and gives first encouraging results. This treatment is less onerous than the previous one, researchers hope to be able to benefit a larger number of patients.
Other treatment for the future, gene therapy: It is capable of producing neurons of a person afflicted by embryonic cloning. These producers of dopamine neurons could be implemented without risk of rejection; this has been done successfully on mice.
Other protocols using other types of cells, for example, neural stem cell, are being tested in animals. They are to genetically modify cells in vitro, to make them produce dopamine, and then to be transplanted.
Finally, another strategy, currently being tested in animals, is designed to prevent the death of neurons, particularly through growth factors involved in their survival.
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