Today (Thusday) is world Parkinson's Day. The health segment
http://sante.lefigaro.fr/actualite/2016/04/10/24845-maladie-parkinson-dix-questions
source: Le Figaro santé 11/04/19
author: Anne Prigent
translation: doxa-louise
10 THINGS TO KNOW ABOUT PARKINSON’S DISEASE
Origin, symptoms, progression, symptoms...an overview of what we know on this World Day.
A crippling disease, Parkinson’s is the second most frequent degenerative disease
after Alzheimer’s. It affects some 150 000 people in France. The name comes from the English physician James Parkinson who first described it in 1817.
- The Symptoms
This neurodegenerative illness is linked to the destruction of dopaminergic neurons.
‘This particular group of neurons can be found in a specific region of the brain: dark matter. They produce a neurotransmitter, dopamine’, explains Professor Marc Vérin, from the Neurosciences clinic at Rennes. Dopamine is necessary for controlling the movements of the body: its lower concentration, linked to a progressive disappearance of neurons, is what causes the illness. ‘But neurons other than those of black matter may also be hit’, continues Professor Vérin. Which explains in part the heterogeneity of clinical manifestations.
Parkinson’ is first and foremost an illness that affects movement. Those who suffer from it are overcome by under-evaluated symptoms that are, for many among them, invisible to the eyes of those around them. ‘There are two important categories of signs of the illness: motor symptoms, of which trembling while at rest well-known to the public, the slowness of movement (bradykinesia) and stiffness, but the illness will also cause non-motor symptoms’, explains Professor Luc Defebvre, neurologist at Rennes’ CHRU
(Regional university hospital).
For most of us, trembling is the sign of the illness most easily recognized. But it is not the most prevalent: it touches 64% of Parkinson patients, according to a study done by France Parkinson. It is a trembling at rest, that is where the part of the body concerned is not moving. It often occurs in but one half of the body and affects an upper limb or, more rarely, a lower one.
The sign most often mentioned by patients themselves is slowness of movement, which affects 88% of them. the loss of dopamine means the loss of automatic movement, thus slowness. As Charcot, the famous French neurologist remarked, they are forever condemned to voluntary movement. simple things like going through a door, lacing up one’s shoes... become an ordeal. Rigidity or hypertonia completes what is referred to as the Parkinson’s triad. ‘I has cramps which would occur unannounced. Thus I dared not hold a child in my arms for fear of dropping him. Other example, the walking movements would no longer follow each other’, tells us Didier Robillard, president of the association France Parkinson, who was diagnosed at 47.
2. Other signs of the illness
The non-motor signs are many and varied and have been increasingly researched in recent times. Thye ar no doubt a consequence of repercussions of the illness on non-dopaminergic cerebral structures. This can be sleep-related problems, hyper-salivation, daytime drowsiness, fatigue, aches, constipation (which touches 60% of patients), urgent need to urinate, depression, hallucinations, cignitive difficulties...
Such signs can appear late in the development of the illness or, inversely, well before the appearance of motor signs. ‘A loss of the sense of smell, constipation, fatigue, slowness in walking, mood change are among the quite precocious signs that can herald the coming of Parkinson’s. But taken in isolation, they are not terribly predictive. It is their appearing together that is noteworthy’ emphasizes Professor Marie Vidailhet, a neurologist at Pitié-Salpêtrière hospital, coordinator for the research group on motor control at the institute for the brain and spinal chord. ‘by contrast, we do know that people suffering from problems with paradoxical sleep have a higher risk of developing Parkinson’s’, she points out. Problems with paradoxical sleep manifest s a loss of muscular relaxation during paradoxical sleep. As a result, patients live through their dreams and perform in their dreams the movements which correspond to the actions in the dream.
3. Those affected by the illness
Parkinson’s affects 150 000 people in france but, contrary to what many believe, this is not an illness which strikes only the elderly: the average age for a first diagnostic is 59. It is nonetheless rare before 40: a mere 10% of cases. Every year, 8000 new cases are declared and, in total, 1% of the population over 60 is hit. Very young people might show rare genetic forms of the illness.
4. The causes
In the majority of cases, we do not know the cause. Of course, there is a genetic
predisposition but it is quite rare. thus it is not a hereditary illness, even if 5% take on a genetic form. Pesticide use in agriculture is increasingly singles out. But age is also an important risk factor. Degeneracy in dopaminergic neurons is caused by genetic and environmental factors. There is not one, but many Parkinson’s diseases. The idiopathic form is seen in 80 to 90% of cases. The other 10 to 20% are referred to as forms of Parkinsonian syndrome. Most frequently, these are caused by drugs such as neuroleptics.
5. How a diagnostic is established
‘The diagnostic is arrived at in a clinical setting and will continue to be so for some time. It is a specialist doctor, in the face of what the patient is experiencing and the loved ones reporting, who will make the diagnostic’ explains Marie Vidailhet. The first criterion is the presence of at least two motor signs. Certain things can occur very precociously
such as micrographics, that is increasingly small hand-writing, which is a form of akinesia.’ Less precision in sport or a good performance in running tied, for example, with foot dystonia can be important signs’, according to Professor Luc Defebvre.
Such discrete signs don’t always lead to people consulting a specialist. Moreover, this pathology can begin by showing non-motor signs:‘There are as many reveals as their are patients’, reminds us Didier Robillard. this is why the diagnostic requires a certain expertise. And is trying for the patient. ‘It is a tsunami. Parkinson’s is a form of suffering both physical and moral. Especially in how it affects how others see one’, claims the president of the association France Parkinson. Professor Vidailhet presents this new state as moving: the patient must learn to live in a new environment which he does not like. ‘I counsel them not to identify with the illness, to keep their identity as individuals and to keep a social life going’ the neurologist forcibly points out.
No complementary biological or radiological exam is of much use. An MRI is sometimes offered to exclude certain causes as responsible. Sophisticated imaging techniques might give some information but they need expert analysis. ‘Exams such as a Dat scan or a Pet scan will show indirectly the loss of dopamine. But with similar Dat or Pet results, patients might show different clinical symptoms because their brains will have compensated the loss differently’ explains Professor Vidailhet. By the time clinical symptoms show up, 50 to 70% of dopaminergic neurons are gone: the illness has been at work for many years. During these silent times, the brain compensates for lower dopamine because of its inherent plasticity. Finding the illness before the appearance of clinical symptoms is only useful for research purposes. Because, for the moment, there is no known treatment.
6. Illness progression
The symptoms and rate of progression of the illness can be very different from one patient to the next. But schematically, the natural evolution of things is in three stages. Once we have a diagnosis, a course of treatment is put forward. The aim here is to replace the dopamine which has disappeared. Because, as Professor Yves Agid, scientific Head of the Institute for brain and spinal chord Paris reminds us, ‘Parkinson’s disease, is like diabetes for the brain with dopamine instead of insulin.’ This line of treatment is remarkably effective and will correct for the dopamine shortfall and control the symptoms of the illness: trembling, slowness, rigidity. ‘This is the so-called honeymoon phase, which can go from three to ten years depending on the individual’,
explains Professor Philippe Damier, neurologist at the CHU, Nantes.
But after many years, the treatment itself will bring on motor complications.
‘Fluctuations in the usefulness of the treatment will bring on a re-appearance of the Parkinson symptoms during the day and abnormal involuntary movements called dyskinesia’, adds Professor Damier. This is the ‘on-off’ period: disruption will occur during the day in a non-predictable fashion. Periods of well-being (‘on’) alternate with periods of blockage (‘off’) or involuntary movement. The third phase is the most difficult because we have symptoms on which treatment is ineffective. Problems in walking become worse with, as a consequence, a loss of balance and falls. Other possible problems: difficulty in speaking - called dysarthria - and the arrival or worsening of cognitive troubles. ‘The latter, of type confusion or withdrawal, can sometimes be badly interpreted by the family’, describes Philippe Damier.
7. Treatment with drugs
There is nothing at the moment that can prevent or treat Parkinson’s. The only available treatments work on the symptoms of the illness. So long as there is no jeopardy to daily living, there is no obligation to treat. Once the symptoms are a problem, drugs become necessary. ‘The aim is to compensate for the lack of dopamine in the brain. We have very effective drugs for that’, explains Professor Damier. The cornerstone treatment is Levodopa, or L-dopa, the immediate precursor to dopamine. An alternative to levodopa, dopamine agonists are molecules that mimic the effects of dopamine at the neuron level. Other drugs work on inhibiting the enzymes which degrade dopamine in the brain. ‘A drug such as Rasagiline, inhibitor to monoamine oxydase B, an enzyme which destructs dopamine, might have a neuroprotection effect. It might be useful to introduce this this early on in the illness’, insists Professor Damier.
Treatment is effective and relatively easy to follow during the said honeymoon period. Later, with the presence of motor and non-motor fluctuations, things get more constraining with patients who need to take meds at fixed times every day of the year, for ever. ‘Each patient has a particular illness profile. Which is why treatments are hand-sown for each and every one’, tells us Professor Defebvre. Dose adaptation is a fine art. ‘But nothing brings with it a comfortable life’, according to Didier Robillard. Moreover, these approaches are not always useful for non-motor symptoms that accompany dopaminergic disruptions.
Once motor symptoms resist treatment, a surgical solution with deep cerebral stimulation can be proposed, under certain conditions. Where surgery is not possible, there are now alternatives. Such would be the apomorphine pump to inject a dopaminergic agonist under the skin. An intestinal continued administration of Levodopa is less frequent because it involves introducing a permanent probe.
8. Side-effects to the drugs
One person in three claims to have chosen to interrupt treatment and, in 45% of cases, this break was motivated by side-effects. Levodopa, the reference approach, is known to provoke after a few years of use abnormal movements and dyskinesia. One third of patients on average have been affected by diskinesia. Meanwhile, this is rare with dopaminergic agonists. This is why, when they were first introduced, these molecules were often prescribed as a first line of treatment. Since then, the drugs have become
notorious and are in the center of legal action because the patients using them had become addicted to gambling, sex...
‘We know today that 15% of patients on dopaminergic agonists present impulse control issues that are difficult to predict’, explains Professor Damier. Incessant jealousy scenes, uncontrollable sexual desire, gambling addiction... these behavioral outbursts can transform the life of the patient and his carers into a living hell. ‘There is no doubt a genetic pre-disposition at work, but at the moment, the records of the patient is all we have to work with’, the neurologist continues. Specialists will thus be more careful where patients have a record of addiction to tobacco, alcohol or faced with a workplace bulimic such as, for example, a hyper-active entrepreneur,.‘It is up to us to question the patient on all the secondary effects they might encounter. This is true for impulse control issues, as with hallucinations under dopaminergic agonists but also levodopa’, judges Professor Defebvre. Once secondary effects are out of control, one needs to adjust treatment and perhaps even stop it.
9. A place for rehabilitation
Parkinson’s often causes physical handicaps. Rehabilitation will then occupy an important place in treatment. Three quarters of patients will go into rehabilitation at one point, according to data from the white book of the association France Parkinson. ‘Physical therapy is useful on condition of also maintaining regular physical activity. It is also the responsibility of the patients to self-treat by maintaining activity as a complement to physical therapy’, explains Professor Vidailhet. Yet studies have shown that people suffering from Parkinson’s spontaneously adopt a less active lifestyle than others in their age group. ‘Nonetheless, continued physical exercise minimizes symptoms and makes one more sensitive to treatment', reveals Professor Vérin.
10. Research
‘We are in the midst of a revolution in our understanding of neurodegenerative illness, and of Parkinson’s in particular’, advances gaily Professor Vérin. There is much work on a particular protein, alpha synuclein. ‘This protein, a natural constituent of neurons, takes on an abnormal spatial form, aggregates a group of neurons, and kills them off. The deposits - known as Lewy bodies - go from neuron to neuron in a Prion-like process, which could explain the development of the illness’, the researcher tells us. This work could result in the use of anti-bodies directed toward this abnormal protein, thus halting the illness.
Other promising leads: the role of mitochondria in neuronal degeneration or again cerebral inflammation. The discovery of the genes involved in the familial forms of the illness will also be helpful in understanding the mechanisms involved. The cure for the illness will be many-faceted. ‘We will no doubt need a combination of therapies to address many mechanisms at the same time’, concludes Professor Yves Agid.
