Parkinson's disease (PD) is the second most degenerative disease of the central nervous system in the world, after Alzheimer's disease. Epidemiological surveys show that the prevalence of Parkinson's disease in European and American countries over 60 years old has reached 1%, and more than 4% for people over 80 years old.
There are more than 2.7 million people with Parkinson's disease in mainland China, and the number of new patients each year reaches more than 100,000. The prevalence is similar to that in Europe and the United States, with prevalence of 1% to 2% in people over 65 years of age and as high as 4% in groups over 85 years of age.
The disease was first systematically described by the British physician James Parkinson in an article he published in 1817 titled Essay on the Shaking Palsy, and in 1997, the European Parkinson's Disease Federation designated Dr. James Parkinson's birthday, 11 April, as World Parkinson's Day.
(Source: Figureworm Creative)
Tremors, stiff limbs, slow movements, insomnia, loss of smell, dementia... These are all significant symptoms of Parkinson's disease. The disease is currently incurable, and as the disease progresses, the symptoms of Parkinson's disease will gradually worsen, which will seriously impair the patient's daily activities.
However, early detection and intervention in treatment can significantly improve the symptoms of Parkinson's patients and maintain their high quality of life.
Pathogenesis of Parkinson's
As early as 4500 years ago, the ancient Indian medical system recorded a disease called "kampavata", which manifested itself in tremor (kampa) and lack of muscle movement (vata), which was first described in detail by the British physician James Parkinson in 1817, but it was not until the early 20th century that the pathology of Parkinson's disease was fully understood.
In 1912, German pathologist Frederick Lewy reported the discovery of neuronal cytoplasmic inclusion bodies in multiple brain regions. In 1919, Tretiakoff observed that the most critical abnormality in Parkinson's disease was the loss of neurons in the substantia nigra pars compacta (SNc) of the midbrain.
In the 1950s, researchers discovered the importance of dopamine and found that its depletion in the basal node was key to understanding Parkinson's pathophysiology and pathobiochemistry.
That is to say, Parkinson's disease is mainly caused by the denaturation of dopaminergic neurons in the substantia nigra and the significant reduction of dopamine content in the striatum. However, the pathogenesis of Parkinson's disease is not fully understood, and genetic and environmental factors are currently considered to play an important role in it.
(Source: Figureworm Creative)
Related studies have shown that oxidative stress, mitochondrial function defects, protein misfolding and aggregation, and glial cell hyperplasia play an important role in the degenerative death of dopaminergic neurons.
1. Oxidative stress: Excessive production of reactive oxygen species (ROS) can lead to oxidative stress, which damages neurons through free radicals and is particularly susceptible to affecting dopaminergic neurons in the substantia nigra.
2. Mitochondrial dysfunction: mitochondrial dysfunction, mitochondrial DNA mutations, nuclear DNA gene mutations associated with mitochondria, and the presence of mitochondrial-related mutant proteins are all related to Parkinson's disease.
3. Protein overexpression and aggregation: In patients with Parkinson's disease, soluble α-Syn monomer initially forms oligomers, then gradually combines to form small fibrils, and eventually forms large and insoluble α-Syn fibers (that is, the main component that makes up The Louis body), while the formation of Lewis bodies in the dense part of the substantia nigra in specific brain regions of the midbrain is one of the main pathological features of primary Parkinson's disease.
(Main causative factors of Parkinson's disease/Source: References[3])
4. Neuroinflammation: Neuroinflammation is one of the characteristics of Parkinson's disease and is closely related to genes such as LRRK2 associated with Parkinson's disease risk. Experiments have shown that neuroinflammation can promote α-Syn misfolding and aggregation to induce innate immunity and adaptive immunity in Parkinson's disease.
5. Ca2+ homeostasis impaired: the activity of dopaminergic neurons is regulated by Ca2+ carriers and Ca2+ homeostasis, changes in mitochondrial dynamics are related to the formation of contact sites between endoplasmic reticulum, and appropriate endoplasmic reticulotic-mitochondrial communication is necessary to maintain mitochondrial bioenergy, Ca2+ homeostasis and cell survival.
Disruption of ca2+ signaling tools and other components can lead to degeneration of fragile dopaminergic neurons due to excessive Ca2+ inflow.
Early symptoms of Parkinson's
Clinical manifestations of Parkinson's disease include motor and non-motor symptoms, symptoms are diverse, the onset is insidious, not easily noticed, and many patients usually find their own motor symptoms under the reminder of family or friends, rather than motor symptoms that can only be detected by themselves and are found late.
Non-motor symptoms
1) Olfactory disorders: hyposonmia or loss of smell is present in more than 90% of patients, usually bilateral, and may precede the appearance of motility symptoms caused by dopamine defects.
Although hypofactory is not present in every patient with Parkinson's disease, its presence or development may be a specific marker of motor symptoms in patients with early Parkinson's disease, especially when hypofactory is associated with other early clinical manifestations, imaging evidence, or biological markers, such as resting tremor and cognitive dysfunction.
2) Anxiety and depression: Anxiety affects 60% of people with PD, including generalized anxiety (anxiety, fear, and annoyance), panic disorder, and social phobia, which are often accompanied by depression.
Anxiety can precede motor symptoms of Parkinson's disease, suggesting that it may be associated with abnormal states of the striatum nigra pathway. Depression is also clinically prevalent, affecting 35% of patients with PD.
Depressive patients with non-Parkinson's disease are less self-aware. In addition, cognitive decline and dementia, psychotic episodes, anxiety, sleep disturbances, and autonomic symptoms have also been associated with an increased risk of depression in Parkinson's disease.
3) Sleep disorders: Sleep and wake disorders affect most people with Parkinson's disease, and their degree increases with the prolongation of the disease. Daytime sleepiness can be distinguished from nocturnal sleep disorders, which include disease- or drug-related insomnia such as intermittent sleep, prolonged wakefulness, RAPID eye movement sleep behavior disorder, periodic limb movements, restless legs syndrome, and akathisia.
(Source: Figureworm Creative)
At night, when the effect of the drug disappears, motor symptoms will reappear, and dystonia, nightmares, hallucinations, nocturia, etc. will exacerbate sleep disorders. Insomnia symptoms in patients with Parkinson's disease may be related to the pathology of the disease, but dopaminergic drugs have little effect on treatment.
4) Autonomic dysfunction: autonomic dysfunction symptoms are common in patients with Parkinson's disease, which may precede motor symptoms, including bladder sphincter dysfunction, gastrointestinal dysfunction, cardiovascular dysfunction, hyperhidrosis, constipation, etc.
The pathological basis of autonomic dysfunction is the loss of neurons and the formation of Lewy bodies in its regulatory region, including the distribution of the hypothalamus, sympathetic and parasympathetic nervous systems, digestive system, heart and urinary system, etc. In-depth research is helpful for the early diagnosis and treatment of Parkinson's disease, which is of great significance for improving the quality of life of patients.
Motor symptoms
Parkinson's motility symptoms are typical, but they appear later than non-motility symptoms, possibly due to the role of neuroprotective mechanisms or automatic compensation mechanisms, such as collateral axon regeneration of residual dopamine neurons.
There are 4 main types of motor symptoms:
1) Tremor: The tremor in the early stage of Parkinson's disease is not typical, most of which is only manifested as a slight tremor when excited or nervous, there is no typical "pill-like" action, and it is related to emotion and attention, and needs to be distinguished from other diseases that cause tremor, such as idiopathic tremor, anxiety and depression, tremor caused by psychotropic drugs and alcoholism.
(Source: Figureworm Creative)
2) Muscle rigidity: the patient has limb stiffness in the early stage, that is, the patient places both elbows on the table, so that the forearm is perpendicular to the tabletop, and the wrist joint is relaxed. For normal people, the forearm and wrist closure are 90° flexion, while the wrist joint in early patients with Parkinson's disease is still more or less straight, like a road sign, called "road sign phenomenon".
The most common early stages of Parkinson's disease are shoulder discomfort and pain, which can be misdiagnosed as bursitis, arthritis, or injury to the cyclomatic muscles.
3) Slow movement: patients show reduced movement at will, slow and clumsy movements, such as slow movements such as fastening clothes and laces, decreased facial expressions and instantaneous eyes, binocular gaze, writing is getting smaller and smaller, broken steps when walking, swing arm movements and amplitude are reduced, speaking speed becomes slower, tone becomes lower, and the speed and amplitude decrease when doing rapid repetitive movements (thumb, index finger to finger).
(Source: Figureworm Creative)
4) Postural balance disorder: In the early stage of the disease, patients with Parkinson's disease manifest themselves as the upper limb swing amplitude decreases, the number of times decreases, the lower limbs drag, and sometimes the whole body freezes during walking, which is called "freezing" phenomenon. At the same time, it is difficult to start and turn, the pace is getting smaller and smaller, the faster and faster it is, it is in a forward rush state, and it cannot be stopped in time, which is called "panic gait".
When you find that you or your family members have the above symptoms, you should seek medical treatment in time so as not to miss the best treatment time.
Prevention and treatment of Parkinson's
Although Parkinson's disease is more common in the elderly population, there has been a trend of rejuvenation in recent years, and studies have shown that some patients have an age of onset earlier than 50 years old, accounting for 5% to 10% of Parkinson's disease.
Although the causes of primary Parkinson's disease are not fully understood, it is generally believed to be mainly related to a combination of factors such as aging, genetics and the environment. Secondary Parkinson's disease is mostly caused by encephalitis, cerebral arteriosclerosis or manganese, carbon monoxide poisoning and other causes.
Therefore, intervention from the following aspects may enable early prevention, early detection, early diagnosis, and early treatment of Parkinson's disease.
1. Prevention and treatment of cerebral arteriosclerosis is the fundamental measure to prevent Parkinson's disease, and clinically it is necessary to seriously treat hypertension, diabetes and hyperlipidemia;
2. Avoid or reduce contact with substances that are toxic to the human nervous system, such as carbon monoxide, carbon dioxide, manganese, mercury, etc.;
3. Avoid or reduce the use of perphenazine, reserpine, chlorpromazine and other drugs that induce tremor paralysis;
4. Strengthen physical exercise and mental activity, delay the aging of brain nerve tissue;
5. When it is found that the elderly have olfactory disorders, sleep disorders, anxiety and depression, upper limb tremors, hand shaking, bradykinsia and other early signs of Parkinson's disease, they should go to the hospital in time to seek early diagnosis and early treatment.
(Source: Figureworm Creative)
If Parkinson's disease is diagnosed, do not be too pessimistic and nervous, although the disease can not be cured at present, but through drug treatment, surgical treatment, botulinum toxin treatment, exercise therapy, psychological intervention, care and nursing, etc., can effectively improve or delay symptoms, avoid or reduce adverse reactions, improve work ability and quality of life.
Among the many treatment methods, drug therapy is the first choice and is the main treatment method in the entire treatment process, surgical treatment is an effective supplementary means when drug treatment is poor, botulinum toxin injection is an effective method for treating local spasms and dystonia, and sports and rehabilitation treatment, psychological intervention and care care are suitable for the entire treatment of Parkinson's disease.
(Drug Treatment Flow of Parkinson's Disease / Source: Guidelines for the Treatment of Parkinson's Disease in China (Fourth Edition))
It should be noted that Parkinson's disease is susceptible to the disturbance of internal environmental instability, and if there is an infection, ion disorder, mental and emotional stimulation, etc., it will aggravate the symptoms of Parkinson's disease itself, such as tremor, rigidity and aggravated mobility difficulties. Therefore, during the treatment of the drug, it is necessary to follow the doctor's instructions and do not arbitrarily change or delete the drug.
Edit: Dr. Spring Rain
bibliography:
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Xiao Xueyang,Wu Zhiyin,Hu Linzhen. Pathogenesis of Parkinson's and its latest therapeutic strategies[J]. Journal of Hubei University (Natural Science Edition),2021,43(5):514-521.] DOI:10.3969/j.issn.1000-2375.2021.05.007.
Wang Yingfei,He Juan,Zhang Xuemin. Research progress on early symptoms and diagnostic methods of Parkinson's disease[J]. Medical Review,2018,24(12):2441-2445. DOI:10.3969/j.issn.1006-2084.2018.12.028.
[5] Parkinson's Disease and Movement Disorders Group, Neurology Branch of Chinese Medical Association, Parkinson's Disease and Movement Disorders Group, Neurologist Branch, Chinese Medical Doctor Association. Diagnosis and treatment of early-onset Parkinson's disease in China[J]. Chinese Journal of Neurology,2021,20(2):109-116. DOI:10.3760/cma.j.cn115354-20201119-00903.