Causes and effects
Parkinson's disease is characterized by the destruction of dopaminergic neurons (producing dopamine, a molecule that controls interneuronal communication) in the brain's substantia nigra. This region of the brain plays an essential role in controlling movement. Consequently, Parkinson's disease primarily affects motor functions.
In addition to these cells being destroyed, their associated neuronal networks are disrupted in other regions of the brain including the subthalamic nucleus, striatum and thalamus. It has also recently been discovered that a protein (alpha-synuclein), in its "diseased" form, is solely capable of triggering the phenomenon of neurodegeneration.
However, the exact causes of Parkinson's disease have not been ascertained, since multiple mechanisms are involved in neuronal degeneration.
Parkinson's disease is associated with several risk factors:
- age, which is the main risk factor, with an epidemiological peak occurring around the age of 70 years;
- environmental factors: exposure to pesticides has been proven to play a role;
- genetic susceptibility factors: genetic variants have been identified, although individually they have no predictive effect. Rare hereditary forms also exist (5%) linked to specific mutations.
How does the disease develop?
Parkinson's disease is associated with three main symptoms:
- tremors occurring at rest and mainly affecting the upper limbs. These affect approximately 70% of patients and are intermittent;
- akinesia, i.e. slow execution and coordination of movements. This symptom mainly affects the ability to walk;
- hypertonia characterized by very stiff limbs. This often results in a forward-leaning posture and affects all muscles in the body.
Parkinson's disease is also associated with other non-motor signs caused by the impact of the disease on other brain structures:
- Sleep disorders
- Intestinal disorders
- Balance disorders
Parkinson's disease is a slow, progressive disease. Initial symptom onset occurs when approximately half of the dopaminergic neurons have been destroyed.
During this initial preclinical phase, which can last 5 to 10 years prior to initial symptom onset, the brain uses its plasticity to compensate, and various prodromes, including increased susceptibility to fatigue and concentration problems may be observed.
Progression occurs in several stages charting disease severity. Following an initial phase, in which clinical signs have no impact on everyday life (Stage 1), the disease progresses toward a final phase in which patients lose their autonomy and are unable to walk (Stage 5).
In 2015, Santé publique France developed a method for identifying individuals treated for Parkinson's disease. At that time, 160,000 people were being treated, which represents 2.5 cases per 1,000 inhabitants.
It is currently estimated that almost 200,000 people are affected by Parkinson's disease in France, with over 25,000 newly diagnosed cases every year.
In total, there are 5 million people with Parkinson's disease throughout the world. This figure may double by 2030.
Parkinson's disease is the second most common neurodegenerative disease in France after Alzheimer's disease and is a major cause of disability in the elderly.
Although very rare in people aged under 45 years, the median diagnosis age is 58 years, and therefore Parkinson's disease affects people who are still of working age.
Parkinson's disease is mainly diagnosed based on clinical signs, which involves examining patients and asking them questions.
Patients should consult their family physician as soon as the initial motor symptoms appear asymmetrically (tremors at rest, changes in handwriting, slower movements). They will then be referred to a neurologist or a center of expertise on Parkinson's disease for confirmation of diagnosis.
Medical imaging (MRI, brain scan) is sometimes offered to patients with mild or not entirely characteristic symptoms as an additional diagnostic measure to rule out other diseases.
Parkinson's disease is a highly debilitating disorder that can cause psychological distress. Once patients are informed that they have the disease, it is important to follow this up by ensuring that they and their families have understood all the information provided and can ask questions about any concerns, treatment, and the impact of the disease.
Treatment and prevention
Since Parkinson's disease is caused by a shortfall in dopamine production, current treatments seek to compensate for this deficiency.
Treatments use two mechanisms to compensate for dopamine deficiency:
- exogenously supplying dopamine through precursors or molecules that imitate its effects;
- inhibiting enzymes that cause dopamine degradation.
Although these treatments help with long-term alleviation of motor symptoms, they do not prevent neuronal degeneration, and are therefore incapable of halting disease progression. Treatment adjustments are therefore required throughout the course of the illness to ensure that efficacy is maintained.
Moreover, these treatments do not improve non-motor symptoms mainly caused by non-dopaminergic imbalances.
After 5 to 10 years, treatments’ effects become inconsistent and patients regularly relapse. Treatments also begin to cause multiple side effects including dyskinesia (involuntary movements), which affect quality of life. These side effects are caused by intermittent administration of dopamine.
At this stage of the disease, two options may be considered for patients presenting with highly debilitating dyskinesia:
- deep brain stimulation using electrodes emitting electrical impulses;
- continuous dopamine administration using a subcutaneous or gastric pump.
Various non-drug treatments may also improve the everyday lives of people with Parkinson's disease. In particular, physiotherapy can help patients address any walking and balance issues, while some swallowing, speech and writing problems can be resolved through speech therapy.
Parkinson's disease is a public health issue. It is now essential to:
- educate healthcare professionals and the public to identify the disease from its initial symptom onset;
- improve diagnostics to enable treatment at the earliest possible stages;
- tackle identified environmental risk factors, particularly exposure to pesticides.
At the Institut Pasteur
The Integrative Neurobiology of Cholinergic Systems Unit, led by Uwe Maskos, examines the role of nicotinic receptors in neurodegenerative diseases.
The Membrane Biochemistry and Transport Unit, led by Thomas Wollert, examines the autophagy mechanism and its deregulation in neurodegenerative diseases.
The Membrane Traffic and Pathogenesis Unit, led by Chiara Zurzolo, examines neurodegenerative disease progression mechanisms and the role of TNTs