Parkinson's disease

Idiopathic Parkinson's disease, commonly called Parkinson's disease, was first described by James Parkinson in 1817 in the An Assay on the Shaking Palsy study. After Alzheimer's disease, Parkinson's is the most common neurodegenerative disease. Symptoms worsen during the course of the disease, although treatment with new drugs and non-drug therapies has significantly improved patients' quality of life.

Parkinson's disease is a disorder of the central nervous system, caused by the degeneration of certain neurons, arranged the production of a neurotransmitter called dopamine, located in the part of the brain called the substantia nigra. Dopamine is responsible for activating the circuit that controls movement, and when a high amount of dopaminergic neurons are lacking, proper and adequate stimulation of the receptors located in the area of ​​the brain called the striatum is lacking, resulting in disturbance of the motor system. The reduction and disappearance of these neurons do not yet have an explanation, and leaves open the debate in the scientific field.

According to the area most affected by the lack of neurons, there are different possible names of the disease.

It is defined as "Parkinson's disease" when the affected area is the substantia nigra and the locus coeruleus; we speak of dementia when the cortex is affected extensively and multisystem atrophy when the nervous systems that innervate the viscera are affected.  

Symptoms

The activity of the motor circuit is strongly affected, and this explains the characteristic symptoms of the disease linked to movement and consisting of tremors, rigidity, slowness in motor activity, and difficulty in walking. Motor symptoms are often associated with neuropsychiatric problems, sensory and sleep difficulties, and disorders affecting the sympathetic component of the autonomic nervous system.

The most obvious symptom and for which the disease was also called "agitating paralysis" is tremor. Characteristically, it is a "resting" tremor, which disappears during voluntary movements but is absent during sleep; it is typically low frequency and resembles the movement of counting coins. Initially, it is one-sided, but later it also involves the other side; worsens in situations of emotional stress. It should be emphasized that in 30% of cases, it may not be present at the onset of the disease.

Another peculiarity of the disease is bradykinesia, which consists of the slowness of movements and which, in the early stages of the disease, is certainly the most disabling symptom, making it difficult to perform those daily activities that require precise control of motility, such as writing or dressing.

The lack of modulation of the inhibitory activity of the ganglia on the motor circuit results in an excessive and continuous contraction of the muscles, which confers rigidity and resistance to the passive movement of the limbs, which can be uniform (like a " lead tube ") or jerky ( " toothed wheel ").

The gait disturbance is generally present in the final stages of the disease and is characterized by a walking that typically occurs in small, crawling steps, with frequent occurrence of the phenomenon of " festination, "that is a progressive acceleration with a flexed posture ( camptocormia ) almost to follow your own centre of gravity. This leads to balance disorders and frequent falls, which can cause bone fractures. The pathognomonic symptom is the so-called freezing (frostbite) or the feet that remain glued to the floor, which is linked to the complete loss of the automatism at the base of the start of the march.

A wide range of other motor symptoms are associated with the fundamental ones that have now been described: amimia (disappearance of instinctive mimic movements), dysphagia (swallowing disorders), bradylalia (slow and monotonous language), micrography (writing that tends to shrink).

As mentioned, Parkinson's can be associated with a complex of neuropsychiatric symptoms that can affect both the cognitive and emotional spheres, generally in the initial stages of the disease and often even before motor disorders arise. In the cognitive field, it is characteristic that, due to a disturbance in the attention process, patients find it difficult to follow a long conversation, and due to the onset of visual-spatial problems, they have difficulty in judging the distance of objects. The disturbance of the emotional sphere is expressed with depression, apathy, and anxiety. Sometimes there is a pathological difficulty in controlling impulses, with consequent compulsive behaviors (bulimia, hypersexuality, ludopathy).

In addition to cognitive and motor symptoms, Parkinson's disease can impair other body functions. Quite characteristic are sleep problems that can manifest themselves with excessive daytime sleepiness or sleeplessness at night. Alterations of the autonomic nervous system (autonomic disorders) affect the sympathetic component of the autonomic nervous system and can cause orthostatic hypotension, excessive seborrhea and sweating, urinary incontinence, and erectile dysfunction, xerophthalmia (dry eyes), and constipation. The onset of sensory disturbances is also possible such as the altered sense of smell, vague and erratic sensations of pain, and paresthesias. All these symptoms can lead to the diagnosis of the disease by years.

Causes

Although the etiology of Parkinson's disease is not entirely clear, the hypothesis of a multifactorial origin of the disease, in which environmental and genetic components interact, is now accepted. Possible etiological factors are heredity, brain injury, infections, endogenous neurotoxins, environmental factors, and altered gene pressures. In particular, it is noted that the onset of metal gradients in the absence of efficient homeostatic responses can be cytotoxic and lead to oxidative damage.

Environmental factors

Certain environmental and occupational factors can increase the risk of developing the disease. These include exposure to exogenous toxins such as pesticides, metals, other xenobiotics, and industrial chemicals, lifestyle (diet and smoking), place of residence (rural environment), and professional activity (agricultural work).

Exposure to pesticides, herbicides, insecticides, and fungicides occurs through the intake of water or contaminated food, by skin contact, or by direct inhalation. Chronic exposure to metals such as manganese, copper, iron, aluminium, and lead increases the risk of developing the disease, particularly in people with a positive family history. A positive correlation between illness, residence, and occupational activity is attributed to exposure to particular chemical compounds used in agriculture.

Eating habits can also affect the variability of Parkinson's disease. Foods rich in animal fats, saturated or unsaturated, and vitamin D positively affect the development of the disease, while foods such as nuts, legumes, potatoes, and coffee appear to play a protective role. There is also an inverse association between cigarette smoking and the onset of the disease.

Genetic factors

Positive family history can increase the risk of developing the disease. Hereditary forms of the disease are caused by mutations identified for the following genes: alpha-synuclein, parkin, dardarine, DJ-1. Approximately 5-10% of patients exhibit an autosomal dominant inheritance pattern.

Other possible contributing causes

Some studies suggest some infectious diseases, such as certain forms of encephalitis, as potential contributors to the development of the disease.

In other studies, Parkinson's disease has been associated with brain injury, particularly trauma accompanied by haemorrhage; however, it is not yet definitively ascertained that trauma can be considered an etiological factor.

THERAPIES

To date, there is no therapy that can cure Parkinson's disease. However, there are various types of drugs that can improve the quality of life of patients.

The best known and most used drug is L-DOPA, which is transformed into dopamine and compensates for the lack of neuro-receptors. Over time, other types of drugs, such as amantadine and bromocriptine, have been developed. Generally, these drugs are alternated, within the therapeutic plan, to avoid and reduce any side effects. Medicines called dopamine agonists are also used within the therapy, which has the function of assisting L-DOPA. These drugs are taken individually at the beginning of therapy, therefore without the aid of other drugs, and only later accompanied by L-DOPA.

There is also the possibility of surgery but is used only in cases of severe tremor and resistant to classic medicinal therapies.

Author: Vicki Lezama