Parkinson's disease

Content

Introduction

Introduction

Parkinson's disease is a neurodegenerative disease caused by progressive damage to certain parts of the brain.

The main symptoms (symptoms) are:

  • involuntary movements of one or more parts of the body (tremor)
  • slowness of movement (bradykinesia)
  • muscle stiffness

In addition to these disorders (symptoms), people with Parkinson's disease can experience various physical and psychological disorders, including:

  • depression and anxiety
  • balance disorders, with the risk of falls
  • reduction or loss of the ability to smell (anosmia)
  • sleep disorders 
  • reduction or loss of memory

According to the official estimates of the national guidelines for the diagnosis and treatment of Parkinson's disease published in 2013, there were about 230,000 Italians affected by Parkinson's disease, a figure destined to increase dramatically over the years due to the progressive aging of the population. Pending the update of the national guidelines, the guidelines of the English National Institute for Health and Excellence of Care (NICE), published in 2017, are considered "good practices".

The disease occurs mainly in people over the age of 65 but in a small number of cases, about 5%, it occurs in people under the age of 50. It is slightly more common in males than in females: 6 out of 10 people with Parkinson's disease are men.

There is still no definitive cure for Parkinson's but drugs are available that allow you to control the symptoms and slow down their progression, improving the quality of life of those affected.

Causes

Causes

Parkinson's disease is caused by the loss of nerve cells in an "area of ​​the brain calledblack substance,in Latin substantia nigra.

Nerve cells in this area produce dopamine, a chemical that acts as a messenger (neurotransmitter) between the different areas of the brain responsible for controlling and coordinating movements. If nerve cells are damaged, dopamine levels in the brain are reduced and areas that regulate body movements do not function properly, causing movement to slow down and lack of coordination.

The loss of nerve cells is a slow process. Generally, the symptoms of Parkinson's disease occur when the loss of about 80% of the nerve cells of the black substance.

The exact causes are not yet known, but numerous studies have hypothesized that at the basis of the loss of dopamine-containing nerve cells there are multiple factors which, interacting with each other, potentiate neuronal dysfunction (multifactorial hypothesis).

Genetic factors

Some research has shown that Parkinson's disease can occur in multiple members of the same family, due to genetic mutations that predispose them to develop the disease. However, the genetic predisposition alone is not sufficient to cause the disease, but in combination with environmental factors increases the risk of developing it.

Environmental factors

Several environmental factors can contribute to the onset of Parkinson's disease. According to some studies, these are pesticides and herbicides used in agriculture, industrial chemicals and other pollutants. However, there is no clear correlation between the disease and exposure to these factors.

Other causes of parkinsonism

The term parkinsonism is used to indicate a syndrome characterized by tremor, muscle stiffness and slowness of movement. Parkinson's disease is the most common type of parkinsonism but there are other, rarer forms that can be traced to a specific and well-defined cause:

  • medications, in this case we speak of drug-induced parkinsonism. Symptoms occur after the use of certain drugs (for example antipsychotics) and, in general, tend to improve with their discontinuation
  • other progressive brain pathologies, such as progressive supranuclear palsy, multisystem atrophy and corticobasal degeneration
  • cerebrovascular diseases, characterized by small brain infarcts that cause damage to different areas of the brain (vascular parkinsonism)
Symptoms

Symptoms

Symptoms of Parkinson's disease usually come on gradually and are initially mild. The order in which symptoms occur and their severity vary from one person to another. However, a person with Parkinson's disease is unlikely to have all of the symptoms.

Main symptoms

The main symptoms of Parkinson's disease are of the motor type, i.e. related to movement:

  • tremor, involuntary swing of a hand, an arm and more rarely of a foot, in conditions of rest
  • slowness of movement (bradykinesia), slowing in the execution of movements that interferes with most of the daily activities and determines the typical slow, awkward and small step gait
  • muscle stiffness (stiffening), constant tension of the muscles that makes it difficult to perform any movement; sometimes muscle stiffness is so severe that it causes painful muscle cramps (dystonia)
  • postural instability,feeling of precarious balance that affects a person while standing still or walking

Other symptoms

People with Parkinson's disease may have numerous other physical and mental (non-motor) symptoms

Physical symptoms

  • balance disorders which can cause frequent falls, with the risk of injury and bone fractures
  • reduction or loss of the ability to smell (hyposmia or anosmia) which sometimes occur several years before other symptoms appear
  • neuropathic pain which can cause unpleasant sensations such as burning, cold or numbness in the limbs
  • urinary disorders, characterized by increased urge to urinate at night or loss of urine (urinary incontinence)
  • constipation (constipation)
  • difficulty in achieving or maintaining an erection (erectile dysfunction) for men
  • decreased desire and inability to reach orgasm (sexual dysfunction) for women
  • dizziness, blurred vision or feeling faint, when moving from a sitting or lying position to a standing position, caused by the sudden drop in blood pressure
  • excessive sweatinge (hyperhidrosis)
  • difficulty in swallowing (dysphagia) which can lead to malnutrition and dehydration
  • excessive saliva production (sialorrhea)
  • sleep disorderssuch as insomnia (little and bad sleep) and hypersomnia (excessive sleepiness)

Mental symptoms

Psychiatric disorders

  • depression and anxiety
  • visual hallucinations (seeing things that don't exist) and delusions (irrational and baseless beliefs)
  • behavior disorders

Cognitive disturbances

  • slowing of cognitive functions, characterized by mild memory problems and difficulty in carrying out activities that require planning and organization skills
  • dementia, a condition that manifests itself with memory loss, speech and thought disorders, orientation difficulties over time and space that progressively worsen to the point of preventing normal daily activities

When to see your doctor

It is essential to consult your family doctor when the first symptoms appear. The doctor, on the basis of the reported symptoms and clinical history, will decide whether to refer the patient to a neurologist specialist (expert in diseases of the nervous system) or to a geriatrician (expert in diseases of the elderly) for further checks.

Diagnosis

Diagnosis

There are no specific laboratory and instrumental tests that allow us to diagnose Parkinson's disease with certainty. Diagnosis is essentially based on symptoms, the patient's medical history, and a careful physical examination.

Clinically, the diagnosis of Parkinson's disease is highly probable in the presence of bradykinesia associated with at least one of the following signs / symptoms:

  • tremor of a part of the body, which usually occurs in conditions of rest; the frequency of parkinsonian tremor is between 4 and 6 hertz (cycles per second)
  • muscle stiffness
  • postural instability not related to primary visual, cerebellar, vestibular or proprioceptive dysfunction (proprioception is the ability to perceive signals from your body, such as recognizing your body's position in space and the state of contraction of your muscles)

To support the diagnosis, a drug test is used with a substance called levodopa: the improvement of symptoms with levodopa indicates with a high probability the presence of Parkinson's disease.

To rule out some conditions that manifest themselves with symptoms similar to Parkinson's disease, a follow-up may be required with the single photon emission brain tomoscintigraphy (SPECT). Brain magnetic resonance imaging is the neuroradiological investigation of choice in patients with suspected Parkinson's disease and, in particular, at onset it is intended to exclude the presence of other pathologies.

The time of diagnosis

The doctor's communication of a diagnosis of Parkinson's disease can cause the person emotional distress and mental distress.

For this reason, the support of family members and health personnel is important, who will be able to provide the treatments and advice necessary to face and manage the disease.

Therapy

Therapy

There is currently no cure for this disease, but there are several treatments that allow you to control its symptoms, improving the quality of life of those affected.

During the early stages of the disease, symptoms are usually mild and no drug treatment is necessary. However, it is advisable to constantly monitor the progress of the disease by means of periodic check-ups by the specialist doctor.

As the disease progresses, symptoms can worsen to the point of compromising the performance of normal daily activities in complete autonomy.

In most cases, people with Parkinson's disease respond well to treatments and their degree of disability remains mild or moderate. In a minority of patients, however, the treatments are not as effective and, over time, the degree of disability increases. Although Parkinson's disease is not fatal, it can make you more vulnerable to very serious or life-threatening infections. Advances in therapy, however, offer affected people a "life expectancy similar to, or nearly similar to, that of healthy people."

The different types of treatments available include:

  • supportive therapies (physiotherapy, occupational therapy)
  • pharmacological therapy
  • surgery (indicated only in selected cases)

According to the guidelines of the English National Institute for Health and Excellence of Care (NICE) it is necessary to involve the patient, family members and / or caregivers in all treatment decisions and to take into account clinical conditions, needs and life circumstances of patients, as well as therapeutic goals and preferences on the potential benefits and side effects of different drugs. The specialist will then prepare a personalized treatment strategy based on the characteristics of the disease. The therapeutic scheme will be reviewed and updated periodically.

Supportive therapies

There are a number of rehabilitation therapies that help you live with Parkinson's disease and control its symptoms.

  • Physiotherapy, the physiotherapist can help the person with Parkinson's disease to alleviate muscle stiffness and joint pain through various methods, in particular with motor rehabilitation. The physiotherapist's goal is to improve mobility and gait, with consequent recovery of the patient's motor autonomy
  • occupational therapy, the occupational therapist proposes practical solutions to facilitate the activities of daily life in which the person with Parkinson's disease encounters greater difficulties, such as dressing, taking care of personal hygiene or going out to shop. In addition, he suggests all the necessary precautions for adapt the home environment to the patient's degree of disability, in order to ensure the highest possible level of self-sufficiency
  • rehabilitation of the voice, language and swallowing, many people with Parkinson's disease have difficulty swallowing (dysphagia) and voice and language disorders. A speech therapist, specialized in the treatment and rehabilitation of these problems, can teach exercises that improve speech and swallowing, indicating any technological aids
  • nutritional advice, some symptoms caused by the disease can be controlled through simple changes in eating habits such as:
    • increase the intake of fiber (found in fruit and vegetables) and make sure to introduce enough fluids to reduce constipation (constipation)
    • eat several times a day with small and frequent meals and increase the consumption of salt to avoid dizziness and the lowering of blood pressure in postural changes (transition from sitting or lying to a vertical position). If necessary, a dietician can be contacted to develop a tailor-made diet and avoid unintentional weight loss

Pharmacological therapy

There are several drugs that can control the disorders (symptoms) of Parkinson's disease. The most used are:

  • levodopa(or L-Dopa)
  • dopamine agonists
  • monoamine oxidase B inhibitors
  • Levodopa
    There levodopa it is the most used drug in the treatment of Parkinson's disease. According to NICE guidelines, levodopa therapy is recommended for patients with early Parkinson's disease whose motor symptoms affect quality of life. It is absorbed by nerve cells in the brain and converted into dopamine, the chemical that transmits messages between neurons that control movement. Generally, the increase in dopamine levels, following the intake of levodopa, results in a marked improvement in motor disturbances. Levodopa is combined with other substances (benserazide or carbidopa) in a single drug, usually in tablets. This combination aims to prevent possible side effects related to the breakdown of levodopa in the blood (nausea, vomiting, changes in blood pressure, excessive sweating) and to increase the absorption of the drug in the brain. Usually, treatment with levodopa begins with a very low dose which is gradually increased until the therapeutic effect is achieved.
    Initially, the drug induces a clear improvement in symptoms but, over the years, its effectiveness tends to decrease due to the progressive loss of nerve cells, no longer in sufficient numbers to absorb the drug. For this reason, the dose of levodopa should be increased according to the course of the disease. It is also recommended to take it between meals, one hour before or two hours after, since foods containing proteins can prevent its absorption and therefore , decrease the amount of drug available in the body. Prolonged use of levodopa can cause side effects such as the appearance of involuntary movements (dyskinesias) and motor fluctuations ("on-off" effects), or the alternation of moments characterized by a good ability to move (on) with others in which a block of movements occurs (off)
  • Dopamine agonists
    Dopamine agonists are substances that mimic the action of dopamine produced by the organism (endogenous) by binding to its receptors and activating them. However, their effectiveness is less than that of levodopa, which is why they are prescribed less frequently. NICE guidelines recommend the choice of dopamine agonists for patients with early Parkinson's disease whose motor symptoms do not affect quality of life. At the beginning of treatment, patients and family members should be provided with information on the adverse events of these drugs, specifically impulse control disorder (such as pathological gambling and hypersexuality, binge eating and obsessive shopping), excessive sleepiness , hallucinations, delirium and mental confusion. As soon as the signs of abnormal behavior appear, often not felt by the person with Parkinson's disease, family members should immediately contact the referring specialist to modify the therapy. Dopamine agonists are available in the form of tablets, patches and injections. If administered in combination with levodopa, they allow the dosage of the latter to be reduced. Other possible side effects of dopamine agonists are:
    • nausea or vomiting
    • tiredness and sleepiness
    • dizziness
    Another possible complication of the therapy is represented by sudden falls asleep that expose you to the risk of accidents if you are driving a car. This serious inconvenience, uncommon, usually occurs when the dose of the drug is increased and tends to resolve when the dosage is stabilized.
    A particular dopamine agonist drug, used in the advanced stages of Parkinson's disease, is apomorphine, administered subcutaneously in one of the following ways:
    • for single injection, to be used as needed as an emergency medicine
    • by continuous infusion using a small pump to carry with you (positioned on the belt, or in your pocket)
  • Inhibitors of monoamine oxidase B
    Monoamine oxidase type B (MAO-B) inhibitors, including selegiline, rasagiline and safinamide, represent another group of drugs for the treatment of Parkinson's disease. These substances block the enzymes that break down dopamine (monoamine oxidase B) causing an increase in dopamine levels in the brain. They can be used in combination with levodopa and dopamine agonists. Safinamide treatment is indicated as add-on therapy to levodopa or in combination with other therapies for Parkinson's disease in fluctuating intermediate and advanced patients.
    Generally these drugs are well tolerated, but in some patients they can cause side effects such as nausea, headache, abdominal pain, high blood pressure
  • Inhibitors of catechol-O-methyltransferases
    Catechol-O-methyltransferase (COMT) inhibitors are only given in combination with levodopa. These drugs prevent the degradation of levodopa by the COMT enzyme, increasing its persistence in the blood and consequently in the brain. COMT drugs are entacapone, opicapone and tolcapone
  • Duodopa
    Duodopa is a particular formulation of levodopa which is usually used in patients with severe motor fluctuations. It is administered by continuous intestinal infusion through a small tube inserted into the abdominal wall, connected to a portable pump. Duodopa treatment is performed only in specialized centers

Surgical intervention

In most cases, Parkinson's disease is treated with drug therapy, but, in some cases, deep brain stimulation neurosurgery may be required.

The surgery involves the implantation of an electrical impulse generator (similar to a cardiac pacemaker) positioned in a "pocket" under the skin of the chest and connected to one, or two, thin electrical wires, inserted in specific areas of the brain. The current produced by the generator passes through the wires and stimulates the area of ​​the brain damaged by the disease. Deep brain stimulation, while not allowing Parkinson's disease to heal, significantly improves patients' symptoms and quality of life.

Treatment of non-motor symptoms (disorders)

In addition to movement disorders, people with Parkinson's may experience a "wide range of non-motor symptoms that need specific treatment. These symptoms are:

  • depression and anxiety, which can be treated with physical exercise, psychotherapy or drug therapy
  • sleep disorders, which can improve with both drugs and non-drug therapy (sleep behavior therapy); for excessive daytime sleepiness, stimulating drugs can be used that increase the release of some neurotransmitters such as, for example, modanafil
  • erectile dysfunction, treatable with drugs
  • excessive sweating(hyperhidrosis), which can be attenuated with specific antiperspirants, botulinum toxin infiltrations, or, in more severe cases, with surgical techniques
  • difficulty swallowing (dysphagia), which can be controlled with a specific diet and use of liquid thickeners. In very serious cases, feeding through a nasogastric tube can be used
  • excessive salivation (sialorrhea), which can be contained by non-pharmacological (swallowing exercises) and pharmacological (botulinum toxin infiltration and surgery) therapies
  • urinary incontinence, treatable with pharmacological and non-pharmacological therapies (exercises to strengthen the muscles of the pelvic wall)
  • cognitive impairments, which can be treated with cognitive-behavioral therapy and drugs

Complementary and alternative therapies

Many people with Parkinson's disease resort to so-called therapies alternatives (acupuncture, phytotherapy, music therapy). Before deciding to use any type of alternative therapy, it is necessary to seek the advice of the reference specialist.

Treatment options for Parkinson's disease: advantages and disadvantages

Treatment Benefits Disadvantages
DRUGS
Levodopa
It is absorbed by nerve cells in the brain and converted into dopamine, a chemical essential for the control and coordination of body movements
  • It is the most effective therapy for Parkinson's disease
  • Treatment with levodopa initially leads to a marked improvement in symptoms
  • In advanced stages of the disease an increase in dosage is necessary
  • It can cause nausea, vomiting, dizziness
  • It can contribute to the appearance of "on-off" motor complications (alternation of moments of good "on" motility and moments of "off" motor block)
  • High doses of levodopa can lead to involuntary movements (dyskinesias)
  • In some patients it has reduced efficacy when taken in close proximity to protein-rich meals
Dopamine agonists
They are substances that mimic the action of endogenous dopamine by binding to its receptors and activating them
  • Compared to levodopa, they have a lower risk of dyskinesias
  • They are also available as extended-release tablets (to be taken only once a day)
  • They can also be administered transdermally (through patches) or subcutaneously, through injections or continuous infusions (see apomorphine)
  • They can induce nausea, vomiting, fatigue, dizziness and episodes of confusion or hallucinations
  • In some cases, they can cause compulsive behavioral disorders, such as pathological gambling and hypersexuality, binge eating and obsessive shopping, hallucinations, delusions, mental confusion
Monoamine oxidase B (MAO-B) inhibitors
They inhibit the effects of the MAO-B enzyme (which transforms dopamine) allowing dopamine to stay longer in the brain (resulting in activation of dopamine receptors)
  • They allow to prolong the beneficial effect of levodopa and reduce its dosage
  • Taken in combination with high doses of levodopa, they can generate or worsen involuntary movements and hallucinations
  • They can cause headaches, joint pain, indigestion, flu-like symptoms and depression
  • Some MAO-B inhibitors cannot be taken in combination with some antidepressants
Catechol-O-methyltransferase (COMT) inhibitors
They increase the persistence of levodopa in the blood and consequently in the brain
  • Suitable for stages of the disease where the benefits of levodopa are short-lived
  • Used in combination with levodopa, they reduce the "off" phase (of motor block) and prolong the "on" phase (of good motility)
  • They can induce diarrhea and abdominal pain
  • Some types of COMT inhibitors are hepatotoxic and therefore require periodic follow-up tests
  • They can increase the side effects of levodopa (involuntary movements, nausea and vomiting)
Amantadina
It reduces dyskinesias and “freezing” episodes. By “freezing” we mean sudden motor blocks that temporarily prevent you from moving your feet
  • Allows you to take higher doses of levodopa
  • It can cause hallucinations and "livedo reticularis" (appearance of cyanotic patches on the skin)
Duodopa
It is a gel formulation of levodopa. It is given by continuous intestinal infusion through a small tube inserted into the abdominal wall
  • Therapeutic alternative for some patients in advanced stages of the disease
  • Allows you to reduce involuntary movements (dyskinesias) and moments of immobility ("off" phase)
  • It can relieve night pain
  • Requires surgery in specialized centers
  • The infusion with pump can present some technical problems (the probe can clog or break)
  • The pump, although small, remains visible
Apomorphine
It is a dopamine agonist, injectable subcutaneously, with improvement of symptoms after a few minutes of taking. It can be given as a single injection (as an emergency drug) or by continuous infusion
  • It acts quickly
  • It can guarantee constant benefit
  • It can reduce the time of motor block ("off" phase) and involuntary movements (dyskinesias)
  • Subcutaneous administration requires the use of needles
  • It can induce excessive daytime sleepiness, and sometimes obsessive-compulsive behavioral disturbances
  • It can lead to the appearance of subcutaneous nodules at the injection site
SURGERY
Deep brain stimulation
Deep brain stimulation involves the surgical implantation of a pulse generator placed in a subcutaneous pocket in the chest and connected to one or two thin electrical wires, inserted in specific areas of the brain. The current produced by the generator passes through the wires and stimulates the area of ​​the brain damaged by the disease
  • Therapeutic alternative for severe uncontrolled cases with drug therapy alone
  • It improves tremor, stiffness and slowing of movements quickly after implantation
  • It allows you to reduce the dosage of drugs and therefore any secondary effects
  • Deep brain stimulation surgery is performed only in specialized centers
  • It presents a risk, albeit minimal, of cerebral haemorrhage
  • It can involve mental confusion, speech and visual disturbances
  • There is currently little data on its long-term efficacy
  • It is only indicated in some patients
Living with

Living with

Since Parkinson's disease is characterized by a slow and gradual progression over time, patients need long-term treatments and to change some habits of daily life.

Useful tips to improve the quality of life of people with Parkinson's disease.

  • physical activity and proper nutrition
    Practicing regular physical activity helps to counteract muscle stiffness, improve mood and relieve stress. Sports activities such as cycling or playing tennis and less demanding physical activities such as walking, gardening and yoga can be enjoyed. People with Parkinson's must pay particular attention to nutrition. The diet must be balanced and include foods belonging to all food groups to ensure the body all the nutrients it needs. There are also numerous measures, such as the adaptation of the home environment, which make daily life easier and safer, allowing for better autonomy
  • vaccinations
    All people affected by chronic diseases, such as Parkinson's disease, are recommended to get vaccinated against the flu every year, during the autumn period. Pneumococcal vaccination is also recommended, to prevent severe respiratory infection, pneumococcal pneumonia

Psychosocial aspects

Knowledge of the disease and its course is essential to be able to manage it in the best possible way. For any doubts regarding your condition, it is advisable to contact your family doctor or specialist. In addition, there are associations of people with Parkinson's disease and their families who can be supportive in addressing the various aspects of the disease. Advice from experienced professionals, such as psychologists or social workers, can be helpful in addressing the emotional consequences of the disease.

Complicated Parkinson's disease and palliative care

Complicated Parkinson's disease refers to the advanced stage of the disease characterized by involuntary movements (motor fluctuations and dyskinesias). This phase can be managed through an adaptation of drug therapy, or, in severe cases, through treatments aimed at controlling pain and all other symptoms that no longer respond to specific antiparkinsonian therapy. In this phase of the disease, palliative care is indicated, which can be provided at home, in hospital or in specialized structures, called hospice.

Bibliography

Bibliography

NHS. Parkinson "s disease (English)

LINK MORE INFORMATION

LINK MORE INFORMATION

LIMPE Foundation for Parkinson's Onlus. Guidelines

National Institute for Health and Care Excellence. Parkinson "s diesease in adults: diagnosis and management

Cartabellotta A, Berti F, Patti AL, Quintana S, Eleopra R. Guidelines for the diagnosis and treatment of Parkinson's disease. Evidence 2018; 10 

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