The Parkinson’s disease is a neurological chronic affecting the central nervous system disorders primarily responsible for progressive engines.

Its causes are unknown. The clinical picture is the result of the loss of neurons in the locus Niger (or “black substance”) and an interference beam nigro-striate. The onset is usually between 45 and 70 years. This is the second neurodegenerative disease after Alzheimer’s disease. Parkinson’s disease is distinguished from parkinsonian syndromes that are generally of different origins, and meet some more severe treatment.

History

Epidemiology

Its prevalence in Western countries increases with age. It is 1 to 2 per 1000 in the general population. It is rare before 40 years. The usual age of onset is about 60 years. She said more often in men over 40 years. It is more important in the elderly, more than 4% in people over 85 years. However, epidemiological studies in this age group do not distinguish Parkinson’s disease Parkinsonian syndromes. Men are more often affected than women, but studies are not unanimous.

This is a major cause of motor disability in elderly patients with stroke.

Non-smokers have a higher risk of developing the disease. Similarly, consumption of coffee could have a protective role, at least in humans.

Pathophysiology

The disruption of the dopamine system is an important characteristic of this disease. There are some structures in the brain of a deficit dopamine (a neurotransmitter, a molecule used as a chemical messenger between neurons, synthesized in an axon terminal, neurotransmitter is released into the synaptic cleft in response to a nerve impulse). The brain changes are not confined only to the sphere and many dopaminergic neurotransmitter systems (serotonergic, cholinergic, glutamatergic, adrenergic) are equally affected.

There have been many advances in the pathophysiology of the disease following the discovery of many genes involved in rare form of the disease. Several brain structures are affected during the disease. The olfactory tubercles and the locus ceruleus are affected primarily reflecting disorders of olfaction and sleep (nocturnal restlessness and nightmares) initial. Then, the structures involved in regulating motor (substantia nigra) located in the upper brainstem will be affected and cause the motor symptoms characteristic of the disease. Finally after several decades of evolution, cortical structures may be affected.

Biological processes may lead suspects neuronal losses are varied: oxidative stress, dysfunctional mitochondria, apoptosis, and accumulation of protein.

Causes

• The causes of this disease are not yet determined. It could be the result of the interaction between a genetic predisposition and environmental cofactors. We suspect many years of environmental toxicants, heavy metals and pesticides in particular, but without evidence of a single cause.
• Exposure to pesticides, it would increase the risk of almost 70%: 5% of those exposed to pesticides might develop the disease as against 3% for the general population. This disease is actually more common in rural and urban areas. The organochlorines are primarily responsible (risk up to 2.4 times higher than normal, whereas the average risk would be doubled for exposure to pesticides in the INSERM and the University Pierre Marie Curie. In France, the Social Security acknowledged in 2006 a case of Parkinson’s disease as an occupational disease for a former farm worker.
• A head injury could be a risk factor. Indeed, we frequently found in the history of Parkinson.
• The job? In France, the disease does not appear in the list of occupational diseases, despite some exceptions10.
• In response, the Federation of CFE-CGC Chemistry wished, in September 2006, will attract “the attention of employers on preventive attitudes to adapt to employees when handling pesticides, “for personal protection details (boots, gloves, mask and overalls) are still rarely used.
• Genetic causes: Several active genes have been identified in families with Parkinson’s
• Mutations in the gene LRRK-2, especially in certain populations where family forms are more frequent.
• Involvement of other genes has been described but is much rarer (so, in particular, the Gaucher disease).
• The gene Pyridoxal kinase is abnormally activated in patients, a mutation of this gene alter the amount or activity of enzymes Pyridoxal kinase (PDXK) that converts vitamin B6 into its active form necessary for production of dopamine. However, premature aging and death of cells that produce dopamine is always associated with Parkinson’s disease. In the case of individualized therapies are hoped in the future;
• Synergy between genetic and environmental factors, including diet, the vitamin B6 is particularly seemed to play an important role (risk factor, efficiency factor treatment).

Diagnosis

The diagnosis should be considered in the finding of very specific symptoms:

1. Hypertonia extra pyramidal called “plastic” as opposed to the hypertonic spastic, that is to say that the sensation of “lead pipe” during passive movement of the limb. This rigidity may assign stepwise (aspect of gear). The general attitude is in flexion (thoracic kyphosis, semi-flexed members) and gives a leaning forward. It is increased by Froment maneuver, still supine (sign of the pillow).
2. Earthquake off the ends including thumb: the patient seems to count his money, or roll of bread. It is slow and steady, which may rarely persist in the attitude. Classically, it disappears during voluntary movements of sleep, is increased by the efforts of concentration such as mental arithmetic, and respects the neck and head but can touch the chin.
3. Akinesia: it is a rarity and slowness of movement. It is also manifested by a disturbance of the facial expression and automatic movements such as the walk. This is the most important sign of the disease. The patient has a poker face, mouth open, eyes rarely blinking. Walking is slow small steps, sometimes interspersed with stops trampling. It is sometimes faster (festination), the patient leaning forward apparently chasing his center of gravity. There is always loss of swinging arms. Reciprocating member rapid test (puppets) is poorly made.
4. The diagnosis is sometimes difficult because symptoms can give the appearance of a depression or have a rheumatic appearance.
5. Other symptoms may be met more or less belatedly: Depression, falls, excessive drooling, oculo-palpebral inexhaustible, a micrograph (calligraphy decreases in amplitude), dysarthria (impaired speech), impaired swallowing disorders behavior in REM sleep, orthostatic hypotension, urinary … The alteration of smell is one of the first signs even though it is difficult to evaluate14. Disorders cognitive or even dementia may occur in the elderly.
6. The diagnosis of Parkinson’s disease is usually clinical. It is based on the demonstration of akinesia associated with another symptom (rigidity, resting tremor, or postural disorder). There are a number of neurological diseases with similar symptoms but which often respond to treatment shortly. These disorders are grouped under the term of parkinsonian syndromes (progressive supra-nuclear palsy, multiple system atrophy, etc.). In theory, the certainty of diagnosis is obtained by studying histology of the brain but the diagnostic criteria currently set to allow diagnosis without much difficulty. In some cases, can be used to achieve a scan brain (DaTSCAN) who can demonstrate the achievement of the striatum. The CT brain and MRI were normal but can eliminate other diseases have similar signs.
7. Under the influence of treatment, the symptoms will change. We see movements appear abnormal movement disorders can sometimes be very impressive. They are parasites varied movements of voluntary movements (open-closed eyes, grimacing, tongue movements, rotation of the head, climbing to a shoulder, rolling the arm or leg …)

Differential Diagnosis

Parkinsonism post-neuroleptics (butyrophenones, phenothiazines), but also atypical antipsychotics and neuroleptic hidden (e.g. Primperan: Metoclopramide). It has also been described after use of certain herbs.

Lewy body disease: Parkinsonism in the elderly beginner quickly associated with cognitive disorders, attention disorders, sleep and visual hallucinations.

Manganism: chronic poisoning with manganese by inhalation in certain occupations (welders, etc.) or ingestion (too high content of manganese in the water) can cause Parkinson’s disease16.

Wilson’s Disease: Diagnosis to evoke in a young patient with a family history.

Progressive supra-nuclear palsy (PSP) or Steele-Richardson disease-Olszewski.

Multi-systematized atrophy: extra pyramidal signs associated more or less pyramidal signs, autonomic (orthostatic hypotension, impotence) or cerebellum (balance disorders).

Corticobasal degeneration: a rare condition resulting in apraxia, unilateral extra pyramidal signs.

Rare poisoning: MPTP (drug), pesticides.

Parkinson vascular stroke affecting the basal ganglia.

Hydrocephalus normal pressure.

There is more than a dozen other causes of tremors, including more frequent, essential tremor, a tremor during movement (or in the maintenance of behavior: postural tremor), and not rest, as parkinsonian tremor. Only a diagnosis by a neurologist to confirm the existence of a specific disease.

Medication

Currently, no drug has demonstrated efficacy on the progression of the disease: there is no cure for the disease. Drug treatments are therefore still purely symptomatic (acting on the symptoms).

The L-DOPA therapy is the most used because the most active. This medicine will be transformed into dopamine in the body and used. The transformation happens in the central nervous system but also throughout the body by DOPA decarboxylase in the blood. For this reason, this treatment is coupled with a peripheral decarboxylase inhibitor or catheco O methyl transferase, which reduces the processing device and thus reduces side effects while multiplying by 10 the availability of the nervous system Central. Side effects such as nausea or vomiting are rare when increasing the dose gradually. L-DOPA has a half life (time at which the molecule is half cleared from the body) ranging between 1.30 and 3 hours.

The drug will therefore be taken and repeated regularly throughout the day to keep blood levels stable, and therefore an ongoing clinical effect. The effect of drugs will change over time due to increased sensitivity of brain receptors with L-DOPA and decreased duration of action of each medication. These two features will respectively lead to fluctuations effect and dyskinesia (involuntary movements). Motor fluctuations may be early. The patient states are blocking during the day requiring schedule changes and the use of sustained-release forms. Dyskinesias occur most often when the rate of L-DOPA is the most important in the blood. They may be delayed by taking dopamine agonists. When they occur, it is necessary to decrease the dose of the unit dose of L-DOPA.

The second major category of medication is the class of dopamine agonists: bromocriptine, cabergoline, pramipexole ropinitole, pirebidil, lisurdide, and apomorphine. These substances act directly on postsynaptic receptors in the nigrostriatal pathway… They are less effective on motor symptoms that L-DOPA. They are still used primarily for younger patients because they delay the use of L-DOPA, which promotes the onset of dyskinesias. These medications can cause side effects including nausea, vomiting, edema, and hallucinations control disorders pulsions. last therapeutic class act by inhibiting monoamine oxidase, an enzyme that catabolises dopamine. The two molecules used for this purpose are the selegiline and rasagiline. These can be replaced for a short duration L-dopa in early disease. They are sometimes used as first-line especially in younger patients in order to save the L-dopa. Certain studies suggest a neuroprotective effect

Other drug treatments exist in particular to optimize the effectiveness of L-DOPA: tolcapone can be given, entacapone.

The importance of the placebo effect is noted in this disease, with an improvement of nearly 15% of cases.

Treatment of Parkinson’s disease has been a French consensus conference whose findings were echoed in the recommendations of the High Authority for Health.

Dietary Measures

A diet rich in protein could reduce the effectiveness of levodopa by competing for its intestinal absorption. But studies have not confirmed the value of a protein diet. Taking the medication at the beginning of the meal is sometimes recommended.

Exercise

Regular exercise (possibly in the context ofadapted physical activities) is essential to maintain mobility, flexibility, balance and to combat secondary effects and symptoms. In addition, regular practice of a sport can increase natural secretion of dopamine. The results of the physical effects of Parkinson’s disease show a significant improvement in function.

SPEECH THERAPY

For disorders of speech, swallowing and micrography ‘ It is too often prescribed by doctors late.

Surgical Treatments

Surgical treatment of symptoms by implantation ofelectrodes for stimulation is available since 1998 in Europe, 2000 to the United States. It was developed in humans Alim-Louis Benabid and Pierre Pollak in Grenoble in 1993, following studies conducted on primates by Abdelhamid Benazzouz in Bordeaux. This technique of deep brain stimulation significantly reduces the three motor symptoms of the disease. An electrode is implanted in the sub thalamic nucleus, and a neuro-stimulator sends electrical impulses, which seems to restore the normal functioning of the system.

This treatment does about 10% of patients, because of the heaviness of the operation and strict inclusion criteria (stage of disease, sensitivity to L-DOPA, age …). This technique should be performed by expert teams. It provides continuous effects similar to those of L-DOPA and limiting dyskinesias and motor fluctuations. The transplant cells fetal is a technique that involves injecting by stereotactic cells derived from products of abortion in the striatum of patients. The difficulty of obtaining the cells, the heaviness of the method and the need for immunosuppression have restricted the development of this technology for the benefit of intracerebral chronic stimulation

Another treatment by electrical stimulation of the motor cortex is under study since 2004 and has yielded encouraging results. This treatment is less onerous than the previous one, the researchers hoped to be able to benefit a greater number of patients.21 But these early results were not confirmed and this track is almost abandoned.

Therapeutic prospects

This technique involves injecting in some areas of the central nervous system viral vectors carrying genes. These genes will be integrated into the genome of host cells and secrete neuro-protective substances or enzymes involved in the synthesis of neurotransmitters. Preliminary studies have shown initial positive results with regard to tolerance in humans, but clinical efficacy remains to be demonstrated.

Stem Cells

This is a track that major therapeutic involves transplanting stem cells in the nervous system. These cells are totipotent and can theoretically be transformed into neural cells. There are still many obstacles, particularly related to cancer risk, before considering therapeutic use in humans. The results remain inconsistent, with greater improvement seen in younger patients.

Other

Treatment with electrical stimulation of the spinal cord is also under investigation and has given (March 2009) very promising results in early tests on mice and rats.

Prognosis

The mortality risk is almost doubled compared to a population not parkinsonnienne; the most common cause is probably lung infections.

Falls are a common complication of the disease.

IMPACT ON THE ENVIRONMENT OF THE PATIENT

In France, the spouse of a person sick with Parkinson devotes an average of 8 hours per day. 52% of spouses of people suffering from Parkinson’s disease limited release without the patient’s home. 47% of spouses Parkinson separate bedrooms or use of twin, 46% use a home help.