Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease and is very disabling. It affects about 150,000 people in Europe. It owes its name to the English doctor James Parkinson who first described it in 1817.

1. What are the symptoms?

This neurodegenerative disease is linked to the destruction of dopaminergic neurons. “This population of neurons is present in a particular region of the brain: the black substance. They produce a neurotransmitter, dopamine,” explains Professor Marc Verin. Dopamine is essential for controlling the body’s movements: the decrease in its concentration due to the progressive disappearance of neurons is at the origin of the disease. “But neurons other than those of the black substance can be affected,” says Professor Verin. This partly explains the heterogeneity of clinical signs.

Parkinson’s disease is first and foremost a disease of movement. Patients are invaded by symptoms that are all the more undervalued because many of them are invisible to everyone: “There are two main categories of signs: motor symptoms, including tremor at rest, which is well known to the public, slow movement and stiffness, but the disease will also manifest itself with non-motor symptoms,” explains Professor Ahlskog, neurologist in Mayo Clinic.

For most of us, tremor remains the most common sign of the disease. However, this is not the most frequent: it concerns 64% of Parkinson’s disease sufferers, according to a survey conducted by the Europe Parkinson association. It is a rest tremor, i.e. when the part of the body concerned does not participate in any movement. It is often limited to one side of the body and involves an upper limb or, more rarely, a lower limb.

The most common sign described by patients is slow movement, affecting 88% of them. The loss of dopamine causes the loss of automatic movements and therefore slowness. As Charcot, the famous European neurologist, said, the patient with Parkinson’s disease is condemned to voluntary movement for life. Simple gestures such as walking through a doorway, tying your shoes become challenges. Rigidity or hypertonia completes what is called the Parkinson’s triad.

2. What are the other signs of the disease?

Non-motor signs are multiple and varied and have been the subject of increasing research in recent years. They are probably the consequence of the disease’s impact on non-dopaminergic brain structures. These may include sleep problems, hypersalivation, excessive drowsiness during the day, fatigue, pain, constipation (affecting 60% of patients), urgency, depression, hallucinations, cognitive problems.

These signs may appear later in the course of the disease or, conversely, occur well before the onset of motor signs. “Loss of smell, constipation, fatigue, slow walking, mood disorders are the main early signs that can signal Parkinson’s disease. But taken in isolation they are not very reliable. It is their addition that makes them predictive,” says Professor Marie Vidailhet, neurologist at Park Hospital, responsible for coordinating the motor control research group at the Brain and Spinal Cord Institute. “On the other hand, we do know that people with REM sleep behaviour disorders have an increased risk of developing Parkinson’s disease,” she says. These disorders of REM sleep behavior are characterized by a loss of muscle atony during REM sleep. As a result, patients live their dreams and perform movements in their sleep that correspond to the action of the dream.

3. Who is affected by the disease?

Parkinson’s disease affects 150,000 people in Europe but, contrary to popular belief, it does not only affect the elderly: the average age of patients at first diagnosis is 59 years. However, it is rare before the age of 40: 10% of cases occur before that age. Every year 8,000 new cases are diagnosed and a total of 1% of the population over 60 years of age is affected. Very young people can be affected by extremely rare genetic forms.

4. What are the causes of this?

In the majority of cases, the causes of the disease remain unknown. Although there is a genetic susceptibility, it is relatively low. It is therefore not a hereditary disease, even if there are 5% genetic forms. The responsibility of farmers for pesticides is also becoming increasingly clear. But age is also an important risk factor. The degeneration of dopamine neurons is believed to be promoted by genetic and environmental factors. There is not one, but Parkinson’s disease. Idiopathic Parkinson’s disease accounts for about 80 to 90% of the cases observed. The remaining 10 to 20% are referred to as Parkinson’s syndromes. The most common are caused by drugs such as neuroleptics.

5. How is it diagnosed?

“The diagnosis is clinical and will remain so for some time to come. It is the specialist doctor, confronted with the feelings of the person concerned and his or her family and friends, who will make this diagnosis,” explains Marie Vidailhet. The first criterion for detecting Parkinson’s disease is the presence of at least two motor signs. Some of them may appear very early on as micrography, i. e. writing smaller, which is a form of akinesia. “Less precise sporting gestures or a drop in running performance linked, for example, to foot dystonia can be revealing signs,” says Professor Luc Defebvre.

But these discreet signs do not systematically lead to a specialist consultation. Moreover, the pathology can start with non-motor signs: “There are as many manifestations of the disease as there are patients,” recalls Didier Robiliard. This is why the diagnosis requires a certain expertise. And it is a test for patients. “It’s a tsunami. Parkinson’s disease is both a physical and moral suffering. Especially because of the way others look at it,” continues the president of the France Parkinson association. Professor Vidailhet compares this new state to a move: the patient must learn to live in a new environment that does not suit him. “Above all, I advise them not to identify with their illness, to preserve their identity as a person and to maintain a social life,” the neurologist insists.

No additional biological or radiological examination is useful. An MRI will sometimes be proposed to exclude certain causes of Parkinson’s disease. Sophisticated medical imaging techniques can provide information but need to be analysed by specialists. “Examinations such as Dat scan and Pet scan will indirectly visualize the dopaminergic loss. But with identical Dat scan or Pet scan results, subjects may express different clinical symptoms because the brains will have compensated for dopamine loss differently,” explains Professor Vidailhet. When clinical symptoms appear, 50 to 70% of dopaminergic neurons are already altered: the disease has been at work for several years. During this silent period, the brain compensates for the drop in dopamine with its plasticity. Detecting the disease before clinical signs appear is useful only for research purposes. Because, for the moment, there is no treatment that can stop its evolution.

6. How does the disease progress?

The symptoms and the rate of change in health status are very different from one patient to another. But schematically, the natural course of the disease is divided into three periods. Once the diagnosis has been made, treatment is proposed. Its objective is to replace the dopamine that has disappeared. Because, as Professor Yves Agid, Scientific Director of the Institute of the Brain and Spinal Cord in Paris, points out, “Parkinson’s disease is brain diabetes with dopamine instead of insulin. This treatment is remarkably effective and will correct the dopamine deficiency and help control the symptoms of the disease: tremors, slowness and stiffness. “This is what we call the “honeymoon”, which will last from three to ten years depending on the person,” explains Professor Philippe Damier, neurologist at the University Hospital of Nantes.

But after several years, the treatment itself will lead to motor complications. “Fluctuations in treatment effectiveness are responsible for the reappearance of Parkinson’s symptoms during the day and involuntary abnormal movements called dyskinesia,” adds Professor Damier. This is the period of the so-called “on-off” effect: the discomfort varies during the day in an unpredictable way. Periods of well-being (“on”) alternate with periods of blocking (“off”) or involuntary movements. The third period is the most disabling because symptoms develop on which the treatment no longer acts. Walking disorders are worsening with, as a consequence, a loss of balance and falls. Other possible disorders include difficulty speaking – called dysarthria – and the development or aggravation of cognitive problems. “The latter, of the confused or withdrawn type, can sometimes be misidentified by the family,” describes Philippe Damier.

7. What are the drug treatments?

There is currently no one who can prevent or cure Parkinson’s disease. The only treatments available are for the symptoms of the disease. As long as they do not interfere with daily life, there is no obligation to treat. When symptoms become troublesome, medication is required. “The objective is to compensate for the lack of dopamine in the brain. We have very effective drugs at our disposal,” explains Professor Damier. The reference treatment is levodopa, or L-dopa, an immediate precursor of dopamine. As an alternative to levodopa, dopamine agonists are molecules that mimic the effect of dopamine on neurons. Other drugs work by inhibiting enzymes that break down dopamine in the brain. “A drug like rasagiline, an inhibitor of monamine oxidase B, an enzyme that destroys dopamine, may have a neuroprotective effect. It seems interesting to set up early in the disease,” insists Professor Damier.

The treatments are effective and relatively easy to follow during the so-called honeymoon period. Then, with the appearance of motor and non-motor fluctuations, they become more constraining for patients who live with drugs to be taken at fixed times every day of the year, all their lives. “Each patient has his or her own evolutionary profile. That’s why the treatments are hand-sewn for each of them,” says Defebvre. An adaptation of the doses which is part of the goldsmith’s work. “But none of these remedies provide us with a comfortable life,” says Didier Robiliard. Moreover, these treatments are not always effective on non-motor symptoms not related to dopamine disorders.

When motor symptoms are resistant to treatment, deep brain stimulation surgery may be offered under certain conditions. In the event of contraindications to surgery, alternatives are developing. This is the case with the apomorphine pump, which injects a dopaminergic agonist subcutaneously. Continuous intestinal administration of levodopa is less frequent because it requires the insertion of a permanent catheter.

8. What are the side effects of the drugs?

One in three sick people say they have already stopped their treatment and in 45% of cases, this break was related to side effects. Levodopa, the reference drug, is known to cause abnormal movements or dyskinesias after a few years of follow-up. On average, one third of patients are aware of these dyskinesias. However, these are rare with dopaminergic agonists. This is why, when they were placed on the market, these molecules were often prescribed as first-line drugs. But since then, these drugs have been in the news and have been at the center of the trial because the patients had become addicted to games, to sex.

“We now know that 15% of patients on dopamine agonists have a pulse control disorder that is difficult to predict,” explains Professor Damier. Incessant jealousy attacks, uncontrollable sexual desire, gambling addiction… these disorders can transform the life of the patient and his entourage into hell. “There is probably a genetic predisposition. But for the moment, only the patients’ histories give us some leads,” continues the neurologist. Specialists will thus be more vigilant when patients have a history of addiction to tobacco, alcohol or bulimia nervosa in their professional activity, such as, for example, a hyperactive company manager. “But it is up to us to ask patients about any side effects they may experience. This is true for impulse control disorders, as well as hallucinations under dopaminergic agonists but also under levodopa,” says Prof. Defebvre. When side effects become invasive, it is a matter of adjusting doses and sometimes stopping treatment.

9. What is the place of rehabilitation in care?

Parkinson’s disease is a common cause of disability. Rehabilitation therefore occupies an important place in his care. Three-quarters of patients use physiotherapy at some time or another, according to data published in the white paper published by the France Parkinson association. “Physiotherapy is effective if it is maintained through regular physical activity. It is also the patient’s responsibility to care for himself by maintaining physical activity in addition to physiotherapy,” says Professor Vidailhet. However, studies have shown that patients with Parkinson’s disease spontaneously adopt a less active lifestyle than the population of their age. “However, sustained physical exercise minimizes symptoms and makes people more sensitive to treatment,” says Professor Verin.

10. Where is the research progressing?

“We are in the midst of a revolution in the understanding of neurodegenerative diseases, and Parkinson’s disease in particular,” enthuses Professor Verin. Thus, many studies are interested in the role of a protein, alpha-synuclein. “This protein, a natural constituent of neurons, takes an abnormal spatial form, aggregates and kills them. These clusters, present in Lewy bodies, spread from neuron to neuron, according to a process called Prion-like, which would explain the progression of the disease,” says the researcher. This work could lead to the use of antibodies against this abnormal protein, thus stopping the disease.

Other avenues studied include the role of mitochondria in neuronal degeneration or brain inflammation. The discovery of genes responsible for familial forms of the disease will also help to better understand the mechanisms of the disease. The remedy that will overcome the pathology will be multiple. “It will probably take a combination of therapy to tackle several mechanisms at the same time,” concludes Professor Yves Agid.