Parkinson's disease: causes, treatment, prognosis
Parkinson's disease is a chronic progressive disease whose cause is still unknown. Typically, there is a breakdown of nerve cells in the brain, which communicate via the messenger substance dopamine, and consequently to an absolute lack of dopamine. This deficiency is blamed for the classic symptoms of Parkinson's disease.
Dopamine: An important messenger is missing
The guiding symptom of the disease is the lack of physical activity. In addition, it often comes in the early stages often to a small-step, vorgesgebeugten gait and a typically one-sided beginning of quiet shaking of the hands. A monotone, quiet voice and the loss of facial expressions are also classic for the onset of illness.
In the course of many other symptoms can be added, which complete the picture of Parkinson's disease. These include, for example, muscle pain, but also depression or dementia. The disease usually occurs after the age of 50 years.
Not curable, but many therapy options
The diagnosis of Parkinson's disease is made after excluding other causes for the presence of neurological symptoms. Since Parkinson's disease is not curable, the treatment aims to improve the condition, maintain independence and improve the quality of life. For this purpose, especially medicines, but also general therapeutic measures such as physiotherapy and occupational therapy and speech therapy are used. In rare cases, surgical procedures are also used.
The symptoms of Parkinson's syndrome can be caused by a variety of causes. But beware, not every Parkinson's syndrome is always the same as Parkinson's disease! The exact definition of the present symptom complex is very important, as the treatment of symptomatic Parkinson's disease differs significantly from that of idiopathic Parkinson's syndrome.
- Parkinson's syndrome: symptom complex of sedentary lifestyle (akinesia) and one of the following symptoms: stiff muscles, trembling, gait and standing insecurity (postural instability)
- Symptomatic Parkinson's syndrome: Parkinson's syndrome arising from another cause (for example, medication, intoxication, or cranial trauma)
- Idiopathic Parkinson's syndrome: also called Parkinson's disease. Parkinson's disease is defined by the presence of Parkinson's syndrome for which no other cause could be found after extensive investigation. Parkinson's disease is thus an exclusion diagnosis.
Parkinson's disease is a condition whose cause could not be found until today. For this reason, it is also called idiopathic disease or idiopathic Parkinson's syndrome.
However, it is believed that many different factors are responsible for the development of the disease. Among other things, environmental toxins such as pesticides or heavy metals are discussed as co-causative agents of Parkinson's disease. In a few cases, a genetic component could be moored as the cause of the disease, but this is rather the exception.
Sinking of the black substance
Regardless of the cause of the disease, Parkinson's disease has revealed characteristic changes in the brain that explain the onset of the disease symptoms:
In the midbrain, a region called black substance (Substantia nigra) causes the destruction of nerve cells that contain the transmitter dopamine. Dopamine is a messenger that is instrumental in the initiation and coordination of movements. A lack of dopamine thus leads to a lack of exercise. Initially, the body is able to compensate well for the loss of dopamine, so that the first symptoms of the disease only occur when already 60% to 70% of the nerve cells have gone under.
Chaos in the messengers
In addition to dopamine, other transmitter systems are affected by the disease. Among other things, the transmitter acetylcholine is involved in the control processes of movement sequences. The loss of dopaminergic nerve cells results in a relative overweight of acetylcholine, which is responsible for the tremor symptoms. In the course of the disease there is a reduction of acetylcholine, which is visible in the form of dementia.
The concentrations of other transmitters, such as those of serotonin and norepinephrine, decrease over time, which can manifest itself in a depressive symptomatology.
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Worth knowing about causes and risks
Parkinson's syndrome is defined by the presence of a sedentary lifestyle (bradykinesis or akinesia) plus one of the following symptoms:
- Muscle Stiffness (Rigor)
- Trembling (tremor)
- Gait and stance uncertainty (postural instability)
The course and the complaints of the illness can be very differently pronounced.Furthermore, there is a whole range of concomitant symptoms that can occur in addition to the main symptoms mentioned.
Lack of exercise (bradykinesis or akinesia)
By definition, there is always a lack of movement in Parkinson's disease.
Bradykinese is understood as a slowing down or depletion of the movements, which can be seen in stepping, facial expressions and gestures. The change in the step pattern is a first indication of the presence of Parkinson's disease: When walking, the arms swing less, the body is slightly bent forward, the passage small steps, and the feet are barely lifted from the ground.
Facial expression and gestures are also diminishing: the face is increasingly masklike, speech and swallowing disorders are becoming increasingly common, while voluntary arm movements are becoming less and less common. The voice loses its breadth of variation, becomes increasingly monotonous and quieter.
Restricted fine motor skills can be identified by a changed typeface, which is noticeable by a decreasing letter size from left to right and a deviation of the font size obliquely from above.
Muscle Stiffness (Rigor)
The rigor refers to an increase in muscle tone of the entire musculature, which also occurs at rest. This often causes pain in the shoulder and neck area, which occur especially at the beginning of the disease on one side and only in the course of both sides.
When the limbs are moved passively, a leaden resistance is felt, which occurs involuntarily and is independent of the speed of movement. In some cases, the so-called gear phenomenon can be detected. Here, the resistance of the extremities when moving through is not always constant, but alternately times higher and lower, so that a passively carried out movement is only jerky or choppy possible.
Just like the Rigor, tremor in Parkinson's disease usually begins one-sidedly. Typical of the tremor is that it occurs only at rest (so-called resting tremor) and, at least at the beginning of the disease, in motion and disappears in sleep. The tremor manifests itself in most cases on the hands, but can also occur on the feet.
Gait and stance uncertainty (postural instability)
The postural instability refers to a disturbance of the holding and adjusting reflexes. Reflexes are involuntary movements that are triggered by a stimulus and run unconsciously. Holding and adjusting reflexes serve to balance the body in unexpected situations and, for example, to prevent falls. In Parkinson's disease, this feature is limited, which prevents unexpected and sudden movements (such as tripping) from being trapped. As a result, falls and amplification of the small-step, cautious course are more common.
Even years before the onset of the actual illness, symptoms may occur retrospectively attributed to Parkinson's disease:
- The limitation or loss of the sense of smell (hyposmia or anosmia) is a possible early symptom of the disease, but is often attributed to the aging process and thus rarely observed.
- Pain in muscles and joints (dysaesthesia) is common, especially in the shoulder area, and can severely affect quality of life.
- Sleep disorders are also an early sign of the disease. In particular, it comes to sleep disorders and insomnia as well as strong involuntary movements during dream sleep (so-called REM sleep behavior disorder). The sleep is due to the reduced sleep duration and reduced sleep quality overall, little restorative.
In the later course of the disease, many other complaints may occur that complete the picture of Parkinson's disease:
- Typical are other changes in the gait pattern such as sudden movement blocks (freezing), the tendency to ever smaller and faster becoming steps (Festination) or a tendency to fall forward (propulsion tendency).
- In addition, cognitive or psychopathological symptoms, such as depression, which affects every second person, or dementia, are often associated.
- In late stages of the disease, bladder function may be limited, which can lead to wetness as well as urinary retention. In many cases, bowel function and potency are also limited by illness and medication.
Parkinson's disease can occur in different forms. Depending on which symptom is in the foreground of the disease, a distinction is made in:
- Equivalence type: The three main symptoms of the illness resting tremor, rigor and akinesia are equally pronounced.
- Tremordominance Type: In this form, tremor is at the forefront of the disease, while the symptoms of akinesia and rigor are minimal.
- Akinetisch-rigider type: In this type, the tremor is absent or is only minimally pronounced.
In general, the tremor is considered to be prognostically favorable. The akinetic-rigid Parkinson's type, however, is more often associated with a rapid development of dementia and is associated with a poor disease development.
It is difficult to detect the disease at an early stage. However, first warning signs should be perceived and clarified early by a doctor.
The first indications of the presence of the disease are inexplicable pain and tension of the muscles in the shoulder and arm area, an impaired sense of smell or taste, a reduction of the handwriting and difficulties in otherwise routinely performed activities such as dressing or brushing. In addition, you may notice that you fall more frequently and more easily or injure yourself or your partner during the dream sleep by strong movements.
Anamnesis & neurological examination
The doctor diagnoses Parkinson's disease mainly based on the existing symptoms. In a complete neurological examination, he examines various major and concomitant symptoms.
Bradykinesis can be studied by alternating movements. For example, you will be asked to screw an imaginary light bulb into its holder. Alternating antagonistic movements are typically slower in Parkinson's disease. Furthermore, there is an increased turnover step number on a 180 degree turn.
Characteristic of the tremor is that he is stronger in peace than in motion and reinforced by stress. So the doctor examines the tremor while keeping your hand still while moving and under stress. For this he lets you count, for example, in steps of 7 backwards from 100 and checks whether the tremor is amplified.
The rigor can be checked by the so-called Froment maneuver. This test is already suitable for early diagnosis, as it can strengthen and visualize a slight rigidity during the examination. For this, the doctor checks the muscle tone on a limb by moving it passively. At the same time you have to perform a certain movement with the other hand. This will prevent you from actively supporting the passive movements that the physician performs on your arm, making an existing rig visible.
The postural instability is usually checked while standing. The doctor will easily unbalance you with a sudden movement and check your unconscious reactivity or reflexes. Parkinson's disease is manifested by an increased fall inclination.
Furthermore, the doctor can notice a quiet, monotonous speech as well as a diminished facial expression. Samples and an odor test may provide further evidence of the presence of the disease.
The so-called L-Dopa Response Test can be performed in suspected Parkinson's disease. For this purpose, the doctor will administer the drug L-dopa on a trial basis and check whether your symptoms have improved after 60-90 minutes. L-dopa is in principle the messenger that is lost in Parkinson's disease. An artificial supply of the transmitter must improve the symptoms.
Imaging of the head should be done at least once during the course of the disease. By means of MRI, for example, other causes for the development of the symptoms can be found, as the Parkinson's disease has no specific features on MRI.
Performing a DaTSCANS (Dopamine Transporter Scintigraphy) allows to visualize the pathways in the brain that work with dopamine and can provide evidence of decreased dopaminergic neuron density. In addition to these methods, other imaging techniques for the detection of Parkinson's disease are available. Depending on the symptoms, the attending physician will choose the right method.
According to the current state of science, Parkinson's disease is not curable, but it can be treated relatively well by the administration of medicines. The anti-parkinsonian agents used are selected according to two aspects: on the one hand on the age of onset and on the other hand on the symptoms in the foreground.
Unfortunately, a well-started therapy can not always be continued in the long term, because over time the body gets used to the medication and at some point does not react to it. Then a dose adjustment or a change of therapy becomes necessary. In addition to the medication there is a second therapy pillar, which consists of general measures such as physiotherapy, speech therapy and occupational therapy.
The aim of drug therapy is to compensate for the lack of dopamine in the brain and thus to reduce mental and physical discomfort as well as to maintain independence for as long as possible.There are various medications available:
- L-dopa (levodopa): is a precursor of the messenger substance dopamine
- Dopamine agonists: bind to the dopamine receptor and mimic the action of the messenger
- MAO B and COMT inhibitors: prevent the breakdown of dopamine and thus increase its effect
- Anticholinergics: reduce the increased effects of acetylcholine, which may be caused by the lack of dopamine
- NMDA agonists: reduce the increased effect of the messenger glutamate, which may be caused by dopamine deficiency
People who develop Parkinson's disease before the age of 70 are usually treated with dopamine agonists. Only when treatment failure or if the side effects of dopamine agonists are too strong, is treated with L-dopa. People who develop Parkinson's disease after the age of 70 are already receiving L-Dopa in first-line therapy.
Reason for this procedure is the inevitable loss of L-dopa, which begins after several years of therapy and should be delayed.
Unfortunately, deficiency of dopamine is not easily compensated by drug administration of the hormone. Because dopamine can not reach its place of action, the brain, via the bloodstream. The reason for this is the so-called blood-brain barrier, which is a barrier between the central nervous system (CNS) and the bloodstream and prevents dopamine in the blood from entering the CNS. Only certain substances can overcome the barrier and reach the brain or nerve cells.
For this reason, L-Dopa must be administered to compensate for dopamine deficiency in the CNS. L-Dopa is a precursor of the active hormone dopamine and has the ability to cross the blood-brain barrier. In the brain, L-dopa is metabolized to dopamine by the enzyme DOPA-decarboxylase and can be effective in the active form. In order to prevent L-Dopa from being converted to dopamine in the intestine, it must always be given a peripheral inhibitor of DOPA decarboxylase, which is normally present in the levodopa preparations.
Do not start with L-dopa too soon
L-Dopa (Levodopa comb®, Levopar®, Medopar®, Restex®, Duodopa®, Stalevo®) is the most effective and best tolerated drug for the treatment of Parkinson's disease. However, it loses its effectiveness over time, so it can only be taken over a period of time. For this reason, a first-line therapy with L-dopa is provided only after the age of 70 years.
The side effects of L-Dopa usually increase with the duration of therapy. This is mainly due to the dose increases that become necessary in the course of therapy. The most common symptoms are:
- Nausea and vomiting
- Restlessness, hallucinations
- Cardiovascular complaints
- daytime sleepiness
Find the right dose - a balancing act
Furthermore, it can lead to so-called hypo- and hyperkinetic Wirkungsfluctuationen. The reason for this is the steady decrease in nerve cells, which can metabolize the L-Dopa to dopamine. Finding the right dosage of the drug is therefore becoming increasingly difficult.
Among the hypokinetic effects fluctuations include freezing, in which there is a sudden movement arrest that can not be breached voluntarily. Furthermore, there may be an on-off phenomenon in which phases of good mobility alternate with phases of poor mobility.
Typical of hyperkinetic effects fluctuations are on- and off-dyskinesia. On-Dyskinesia expresses as worm-like to extending movements of the extremities that can not be controlled willingly. They speak for too high dopamine levels. On the other hand, off-dyskinesia are painful cramps, especially of the legs at low dopamine levels.
When taking L-Dopa, it must be taken into account that protein-rich food reduces the absorption of the drug in the intestine. For this reason, L-dopa should ideally be taken 30 minutes before or 2 hours after a meal.
Due to the loss of effect or the increasing side effects of L-Dopa therapy over time, the treatment of Parkinson's disease in the early phase is started with a dopamine agonist. Dopamine agonists sense the effect of dopamine by occupying and activating the same receptors in the brain. The function of dopamine is thus replaced in principle.
Dopamine agonists are further divided into two groups:
- The group of ergot dopamine agonists combines the older substances bromocriptine (Pravidel®, Kirim®), lisuride (Dopergin®) and pergolide (Parkotil®). Among these drugs, increased connective tissue growth of the heart valves may occur, which is why they should not be taken in pre-existing valvular heart disease and are generally rarely used.
- The non-ergot dopamine agonists ropinirole (Adartrel®, Requip®, Ropinal®) and pramipexole (Daquiran®, Sifrol®) do not have this side effect. They are the further development of ergot dopamine agonists and generally better tolerated.
Advantage: The effect does not diminish
Unlike L-Dopa, the effect of dopamine agonists does not decrease in the course of therapy. Also, an increase in dose is usually not mandatory.
Dopamine agonists may cause the following side effects, especially at the beginning of therapy:
- Nausea and vomiting
- stomach pain
MAO B and COMT inhibitors
Physiologically, dopamine is degraded by two enzymes in the brain: monoamine oxidase B (MAO-B) and catechol-O-methyl transferase (COMT). Inhibitors of these enzymes prevent the breakdown of dopamine and thus ensure a longer duration of action by increasing the dopamine concentrations in the CNS.
MAO-B inhibitors such as selegiline (Antiparkin®, Jutagilin®, Movergan®, Selepark®, Xilopar®) and rasagiline (Azilect®) and COMT inhibitors such as entacapone (Comtess®) and tolcapone (Tasmar®) are commonly included mild symptoms prescribed or administered in combination with L-Dopa. The side effects are similar to those of the dopamine agonists.
Anticholinergics are drugs that reduce the effect of the messenger acetylcholine. In Parkinson's disease, the lack of dopamine leads to a relative oversupply of acetylcholine, which is responsible for the tremor and the slowing of movement. By administering anticholinergics such as biperiden (Akineton®) these symptoms can be improved.
Acetylcholine: too little is not good either
Anticholinergics have a wide range of side effects, as acetylcholine as a messenger not only plays a role in the brain, but also on numerous other organs. For this reason, anticholinergics are now rarely used for the treatment of Parkinson's disease.
The main side effects are:
- dry mouth
- urinary retention
- Increased sweating
- Cognitive impairments
- Worsening of dementia
Just as anticholinergics regulate the excess supply of acetylcholine, NMDA antagonists such as amantadine (Amixx®, PK-Merz®, Tregor®) reduce the effect of the transmitter glutamate, which is more active in Parkinson's disease. NMDA antagonists are not used as a sole treatment regimen, but always in addition to treatment with L-dopa or dopamine agonists. Amantadine can cause hallucinations, confusion and swelling of the ankles.
Due to the highly developed and very successful drug therapy, surgical procedures, such as the implantation of a brain pacemaker, are rarely used today. In some cases, an operative therapy for the treatment of Parkinson's disease but be promising. The use of a brain pacemaker, however, may only be carried out under certain conditions and is considered as a therapeutic option only if medical treatments have failed.
In this form of therapy, which is also called deep brain stimulation, electrodes are used in certain areas of the brain that deliver electrical impulses. In this way, nerve cells can be specifically stimulated without damaging the surrounding tissue. The aim of deep brain stimulation is to improve the symptoms of Parkinson's disease, but it can not prevent progression of the disease.
Rehabilitative therapy forms
In addition to drug therapy rehabilitative therapies such as physiotherapy and ergotherapy, but also the speech therapy are of great importance for the treatment of Parkinson's disease.
Physiotherapy aims to maintain mobility, walking and stability as long as possible. Targeted movement and coordination exercises can be used to liquefy movement sequences and to train adjusting and holding reflexes. Furthermore, relaxation exercises can have a positive effect on the tremor.
In occupational therapy, the independent handling in everyday life is learned and practiced. These include not only the dressing and undressing as well as the personal hygiene, but also the preparation of the food, the doing of laundry and shopping. In addition, the use of aids and the conversion of the home environment to include occupational therapy.
Logopedics is used to train speech, speech and swallowing ability. Also facial expressions and gestures can be practiced.
Helping people help themselves
Dealing with the diagnosis of Parkinson's disease is difficult for both the sufferer and relatives. Because the disease progresses chronically and ends fatally. For this reason, not only physical ailments but also mental and psychological complaints should be treated.
Self-help groups are a good way to exchange experiences about the disease, to discuss fears, and to get information about new forms of therapy. Even a psychotherapist can accompany you through the illness as well as in dealing with dying.
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Everything worth knowing for the treatment of Parkinson's disease
Parkinson's disease varies very individually. Typically, however, the disease progresses slowly but steadily and can not be stopped by medication or surgery. While some people do not feel much of the disease over many years, others have clear symptoms from the beginning and need help early on.
Quality of life also with Parkinson's disease
According to the current state of science, Parkinson's disease is not curable. Nevertheless, the quality of life can be increased by the right treatment and the disease progression can be clearly delayed.For this reason, it is important to have a first suspicion of the existence of the disease clarified at an early stage. The further the disease has progressed, the harder it will be to find the right, individually tailored treatment and positively influence the course of the disease.
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Questions and answers about the course and prognosis
Everyday life with Parkinson's disease
Author: Lisa Wunsch
Gerd Herold et al .: Internal Medicine 2015, Gerd Herold, 2015.
Peter Berlit: Clinical Neurology, Springer Verlag, 2006.
German Society of Neurology: S-3 Guideline Idiopathic Parkinson's Syndrome, http://www.dgn.org/leitlinien/3219-030-010-idiopathisches-parkinson-syndrom, last accessed on 06.03.2017.