Parkinson's Disease

from Wikipedia, the free encyclopedia
Classification according to ICD-10
G20 Primary Parkinson's Syndrome
G21 Secondary Parkinson's Syndrome
G22 * Parkinson's Syndrome in Diseases Classified Elsewhere
ICD-10 online (WHO version 2019)
Illustration of Parkinson's Disease by Sir William Richard Gowers from A Manual of Diseases of the Nervous System, 1886

The Parkinson's disease or Parkinson's disease (more synonyms : Idiopathic Parkinson's disease (PD) , Parkinson's disease , colloquially Schüttelkrankheit , older name: paralysis agitans for " Shaking / trembling paralysis ") is a slowly progressive loss of nerve cells. As an incurable neurodegenerative disease, it is one of the degenerative diseases of the extrapyramidal motor system. Approximately one percent of the world's population over the age of 60 is affected by this disease. Parkinson's is the second most common neurodegenerative disease in the world.

Parkinson's disease is characterized by the death of the dopamine-producing nerve cells in the substantia nigra , a structure in the midbrain . The lack of the messenger substance dopamine ultimately leads to a reduction in the activating effect of the basal ganglia on the cerebral cortex and thus to movement disorders.

The main symptoms (also called cardinal or core symptoms) are:

  • early symptoms (are important in order to dampen the progression of the disease through treatment as early as possible - as many years before the onset of the motor symptoms - because of indications of the possible Parkinson's disease)
    • Years before the onset, smell disorder
    • Mood swings (mild irritability) with mild depression
    • constipation
    • the disruption of dream sleep through atypical strong movements during (in a healthy state usually motionless) REM sleep (up to screaming or lashing around)
  • main stage motor disease (low dopamine levels)

The current definition of Parkinson’s syndrome requires that the cardinal symptom bradykinesia or akinesia occur in combination with at least one of the other symptoms ( rigidity , tremor or postural instability ). In addition, various sensitive , vegetative , psychological and cognitive disorders are possible.

To date, there is still no possibility of a causal treatment for Parkinson's syndrome, which is why only treating the symptoms is possible. As the disease progresses, several drugs are often combined that have to be taken at ever shorter intervals in order to achieve sufficient effectiveness and to avoid fluctuations in effectiveness. Advanced therapy options include continuous apomorphine infusion, continuous L-dopa infusion or deep brain stimulation.


The term Parkinson's Syndrome (also called Parkinsonism ) is a generic term for diseases with the above-mentioned main symptoms. The most important disease treated here is Parkinson's disease , an idiopathic disease (i.e. without known external or genetic triggers). However, if there is a definable external cause, it is called secondary or symptomatic Parkinson's syndrome . If there is a neurodegenerative clinical picture with a different pattern of damage, sometimes with further symptoms, one speaks of atypical Parkinson's syndromes .

This results in the following classification of Parkinson's syndromes:

  1. the idiopathic Parkinson's disease (IPS), the subject of this article
    • with approx. 75% the most common Parkinson's syndrome
  2. familial Parkinson's syndrome
    • genetically determined, inheritable forms, rarely, named after the respective gene location (e.g. PARK1)
  3. symptomatic (secondary) Parkinson's syndromes
  4. Parkinson's syndromes in the context of other neurodegenerative diseases (atypical Parkinson's syndromes)


The disease was first described in 1817 by the English physician James Parkinson in the monograph An Essay on the Shaking Palsy ( A Treatise on Shaking Palsy ). Parkinson's already pointed to the slow progression of the disease. He suspected the cause of the paralysis to be a disorder of the spinal cord in the cervical area, which was refuted in 1960 when Arvid Carlsson discovered that the lack of the body's own messenger substance dopamine in certain regions of the brain stem is the cause of Parkinson's disease. However, the symptoms of Parkinson's disease have been known since ancient times. The tremor was first described more precisely by Celsus as an affliction to be treated in older patients.

April 11th of each year was in 1997 by the European Parkinson's Disease Association as World Parkinson's Day proclaimed.

Well-known patients with Parkinson's disease were, for example, Wilhelm von Humboldt , Adolf Hitler , Pope John Paul II , Muhammad Ali and Michael J. Fox .

Age of onset and frequency

The disease usually begins between the ages of 50 and 79 (peak 58 to 62 years of age). Parkinson's syndrome can rarely occur before the age of 40. In the 40 to 44 age group, around one in 10,000 people is affected. The rate of manifestation of the disease increases with age up to about the age of 75, then it decreases again. About 1.5–2.0 percent of those over 80 years of age develop Parkinson's syndrome. In Germany, it is currently assumed that 300,000–400,000 people are sick.


Dopaminergic projections in healthy people (left) and in Parkinson's disease patients (right); red arrows stand for inhibition and blue arrows for target structure stimulation

Functional level: dopamine deficiency

The Parkinson's disease is a degenerative disease of the extrapyramidal system (EPS) or of the basal ganglia . This leads to the death of nerve cells in the pars compacta of the substantia nigra (also nucleus niger , "black core"), which produce dopamine and transport it through their axons into the putamen . The first signs of disease are only noticed when approx. 55% to 60% of these dopaminergic cells have died.

The dopamine deficiency ultimately leads to an imbalance in the function of the basal ganglia in two ways (see picture). The messenger substance glutamate is relatively in excess. Ultimately, the globus pallidus internus inhibits the motor activation of the cerebral cortex by the thalamus . This leads to the main symptoms rigor, tremor and hypokinesis (see below), but also to a slowdown in mental processes (bradyphrenia).

In addition to the dopamine deficiency, changes in other neurotransmitters were also found. In some regions of the brainstem, for example, there was a lack of serotonin , acetylcholine and noradrenaline .

Cellular level

Research and the identification of the inherited forms have shown that Parkinson's disease (MP) is not a uniform disease, but a heterogeneous group of diseases with a spectrum of clinical and pathological manifestations (PARK1 to PARK13). Monogenic forms of Parkinson's disease are responsible for about five to ten percent of all patients with Parkinson's disease. Among these, point mutations of the alpha-synuclein gene ( SNCA gene, PARK1 ) are of particular interest, since alpha-synuclein (SNCA) is the main component of the Lewy bodies in familial and sporadic Parkinson's disease. The PARK1 locus has been mapped in a large family with dominantly inherited Parkinson's disease and Lewy body pathology; two other point mutations with high penetrance have been identified in large families, but not in patients with sporadic Parkinson's disease.

Notably, SNCA aggregates were identified in the presynaptic fraction of human brain tissue in 2007, possibly reflecting an early synaptic disorder, although the exact relationship between aggregation, cellular dysfunction and cell death is not yet known. In addition to changes in the amino acid sequence, duplications and triplications also lead to an increase in the tendency of the protein to form oligomers and fibrillar aggregates, so that the regulation of SNCA expression and translation has an important, at least modulating, significance. Changes in regulatory regions of the SNCA gene could also be associated with a higher risk of developing Parkinson's disease. Several studies have found associations of different genetic variants (single nucleotide polymorphisms; SNP) in the promoter region and other sequence sections of the SNCA gene with sporadic Parkinson's disease (PD Gene Database). Studies from 2008 suggest a possible association of individual SNPs in the non-coding sequence with the level of SNCA expression.

Recent research also suggests an autoimmune component. It was possible to detect α-synuclein peptides which, under laboratory conditions as antigens, lead to the activation of previously identified, frequently changed MHC molecules .

Some of the most important insights into the role of α-synuclein in the development of the disease at the cellular level were obtained from experiments with genetically modified breeding lines of the nematode Caenorhabditis elegans .

External causes

Certain toxins, so-called neurotoxins , which damage the substantia nigra, are considered as external triggers for Parkinson's disease . As a rule, these were absorbed by those concerned either as part of their work or as environmental toxins.

In California in the early 1980s, intravenous use of pethidine contaminated with MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) quickly elicited Parkinson's-like symptoms in young drug addicts that were successful could be treated with L- Dopa (see below ). The effect of the MPTP is that it is converted in the brain into the actively toxic molecule MPP + (1-methyl-4-phenylpyridinium). This has a structure similar to a dopamine molecule, so that it can penetrate the dopamine-producing nerve cells via the dopamine transport system. With increasing accumulation of the MPP + in the cells, it increasingly unfolds its toxic effect by suppressing important metabolic processes there.

Against this background, the herbicide paraquat is suspected of causing Parkinson's syndrome. Paraquat is structurally very similar to the MPP + . Studies carried out in Canada have shown a connection between the use of large amounts of paraquat and a well above average number of Parkinson's cases in the population of the corresponding region. Another pesticide that is thought to cause Parkinson's disease is the insecticide Rotenone . In animal experiments it could be shown that the uptake of Rotenone leads to the release of alpha-synuclein (SNCA), an endogenous protein which, analogous to MPP + , has a toxic effect on dopamine-producing nerve cells and can cause their degeneration. In France, Parkinson's has been recognized as an occupational disease by farmers since 2012 if they have been in contact with pesticides for at least ten years. In a ruling by the Regional Social Court (LSG) in Essen in 2013, Parkinson's was recognized as an occupational disease in a German farmer who had already died and who had worked with lindane , among other things .

According to US American and Korean studies, exposure to degreasing and cleaning agents based on trichlorethylene and perchlorethylene can be linked to Parkinson's disease. If people were exposed to the substances, their risk of Parkinson's was nine times higher.

Octenol , a natural metabolic product and the like a. of mold, has been shown to cause dopamine imbalance in Drosophila and human cell lines. Octenol vapors in rooms with mold infestation could therefore also be an external factor in the development of Parkinson's disease.

Immunohistological findings on mouse brains with and without previous traumatic injury show Parkinson's-typical changes in the former group.

Other external causes are generally craniocerebral trauma (SHT; "closed head / brain injuries") and infections. In laboratory mice that had been taught TBI, brain changes typical of Parkinson's were detected after 30 days. Although mild TBI (concussions) are also discussed as a cause of Parkinson's disease in humans, a 2014 meta-study found that there was little high quality research on this and that the best available evidence does not support a causality between mild TBI and Parkinson's disease. In a case-control study of any head injuries, with or without temporary loss of consciousness, no increased risk of later Parkinson's disease could be determined either.

Findings of high-resolution ultrasound of the vagus nerve, accessory nerve and
phrenic nerve in Parkinson’s patients and control persons show atrophy of the vagus in Parkinson’s patients.

The so-called dual-hit hypothesis is based on a possibly viral pathogen that infects the brain from the nose or stomach via the vagus nerve and causes a form of Parkinson’s associated with Lewy bodies . A cohort study published in 2015 confirmed this hypothesis: the severing of the branches of the vagus nerve leading to the stomach ( vagotomy ) is a surgical treatment for gastric ulcers that is no longer common . For about 15,000 Danes who had undergone a vagotomy between 1977 and 1995, it was determined that in the case of a truncular vagotomy (complete severing of all branches of the vagus leading to the stomach) their Parkinson's disease rate after 20 years compared to the control group (150,000 Danes who had not undergone a vagotomy) almost halved. In patients who had only received a selective vagotomy (cutting through only a few branches of the vagus leading to the stomach), no reduction in the risk of the disease was found after 20 years. A Swedish study published in 2017 came to a similar conclusion.


The disease begins insidiously and then progresses throughout life, the symptoms become stronger and therefore more easily recognizable. The Idiopathic Parkinson's syndrome typically begins on one side (on one side and remains more in the course); An early sign is, for example, the reduced and later missing swinging of an arm when running. It is not uncommon for shoulder pain and unilateral muscle tension to occur, which lead the patient to the orthopedic surgeon first.

Cardinal symptoms

Parkinson's syndrome is defined by the presence of bradykinesia or akinesia and one of the three other key symptoms ( rigidity , tremor , postural instability ).

Akinesia (also bradykinesia or hypokinesis)

This general sedentary lifestyle is a prerequisite for diagnosing Parkinson's disease. It is noticeable in all movements. Muscle play is reduced, which determines facial expression ( masked face , hypomimia ), speaking becomes quiet and indistinct ( microphones ), swallowing is delayed (apparently increased salivation - pseudo-hypersalivation ), and the dexterity of the hands decreases, especially when moving quickly (Typeface becomes smaller - micrograph ), trunk movements are difficult (reduced repositioning during sleep), the gait becomes small steps and shuffles.

This obligatory sign of illness must have at least one of the following three symptoms:

Rigor (also rigidity)

This denotes muscle stiffness due to an increase in muscle tone . It is caused by involuntary tension in the entire striated muscles and often leads to muscle pain. Outwardly visible are a slight flexion of the elbow joint , torso and neck, and later the knee joints . With passive movement of the joints of the upper and lower extremities, the so-called gear phenomenon occurs. Muscle groups close to the body are often more affected ( axial rigidity ). A bent incorrect posture of the trunk due to the increase in tone is called camptocormia .

Resting tremor

Mutual tension of opposing muscles creates a relatively slow tremor ( antagonist tremor - four to six beats per second, rarely up to nine beats per second), which decreases with movement. It is typical for idiopathic Parkinson’s syndrome (75%) and less typical for atypical Parkinson’s syndrome (25%); the tremor is also emphasized on one side. Tremor is the most obvious symptom, but it also occurs as an essential tremor or in cerebellar diseases, so that it can mislead people into a misdiagnosis.

Postural instability

The reduced stability when holding the body upright is due to a disruption of the righting reflexes . The small but quick reflex compensatory movements are delayed so that there is an unsteady gait and stance. The turning movement becomes unsteady, and the patients stumble. You are afraid of falling; this fear of falling can affect them in addition to the motor disability. Atypical Parkinson's syndrome must be taken into account in the case of severely disturbed righting reflexes.

The different symptoms can be differently pronounced in the individual sick or completely absent; Appearance and strength also change during the day. A distinction is therefore made between the forms of Parkinson's disease in the akinetic-rigid type , tremor-dominant type and equivalence type .

Optional accompanying symptoms

In addition to these cardinal symptoms, there are other symptoms to varying degrees in the course of the disease:

Sensitive symptoms
  • a decrease in the sense of smell ( hyposmia ) is common and can often precede Parkinson's disease as an initial symptom.
  • Parasitic sensations ( dysesthesia ) are frequently reported, but the cause is not precisely known.
  • Pain occurs particularly in the joints and muscles (see above).
Vegetative disorders
  • An ointment face (greasy, shiny facial skin) is the result of increased sebum production (together with hypomimia).
  • In the advanced stage of the disease, there are circulatory disorders (orthostatic hypotension). It is not uncommon for blood pressure to rise when lying down and then drop when the body is upright. This can lead to brief loss of consciousness with falls (orthostatic syncope). Patients are then occasionally (incorrectly) treated with drugs for high blood pressure. A marked instability of blood pressure that occurs early in the course of the disease suggests an atypical Parkinson's syndrome.
  • Bladder dysfunction significantly impairs patients in social life. Usually at the beginning there is a sudden strong urge to urinate, often even with small quantities ( pollakiuria ). The onset of micturition disorders early on (i.e., either before or within three years of onset of motor symptoms) is characteristic of atypical Parkinson's disease.
  • Sexual dysfunction is common and typically affects the libido .
  • Movement disorders of the gastrointestinal tract can lead to both diarrhea and constipation and have a strong influence on the absorption of drugs: Diarrhea leads to underdosing because more of the administered active ingredients than pharmacologically calculated leave the body prematurely unabsorbed. Constipation leads to overdose because more of the administered active ingredients than pharmacologically calculated remain in the body and are absorbed; In this case, the different plasma half-lives of the active ingredients also result in an undesirable shift in their proportions.
  • Temperature regulation disorders lead above all to a reduced heat tolerance due to a disruption of reflex sweating and reflex vasodilation when warm. With advanced disease, this can lead to life-threatening high fever conditions. Heavy sweats occur especially at night.

Vegetative disorders that appear early in the course of the disease are considered to be an indication of atypical Parkinson's syndrome.

Mental changes
  • A depressed mood can precede the diagnosis by years as an early symptom. It affects at least 40 percent of patients over time.
  • A slowdown in thought processes, classically referred to as bradyphrenia , is an expression of the general drive disorder. It is considered pseudodementia, as thinking is only slowed down, but not impaired in terms of content.
  • The disruption of the assessment of distances and speeds (visuospatial attention) represents a hazard in road traffic, especially in connection with motor restrictions. It corresponds to a disorder in the frontal lobe .
  • Illusions are mostly the result of dopaminergic drugs. They initially lead to benign (= benign) hallucinations, which the person concerned recognizes as a mirage. For example, people who are not present are seen in the room. This symptom does not appear until later in the disease. In the case of additional subcortical dementia , visual and acoustic hallucinations can develop up to a scenic experience that is mostly perceived as extremely threatening, for example being incarcerated. In this state, the patients can react aggressively in panic, which is not infrequently misunderstood and leads to incorrect therapeutic consequences. Long-term exposure to hallucinatory hallucinations, especially acoustic hallucinations, can take on a life of its own and lead to lasting mental illnesses such as paranoia . A special feature of the cognitive disorders in Parkinson's disease is the often strongly fluctuating disturbance of attention with repeatedly lucid (clear) moments.
  • A real dementia is a presumed form of the idiopathic Parkinson's syndrome, the Lewy body dementia .

The psychological changes are of considerable importance for the everyday handicap of Parkinson's patients and are often underestimated because they are not as obvious as the motor phenomena.

More symptoms

Parkinson's dementia

Parkinson's dementia refers to dementia symptoms that arise in the course of Parkinson's disease. 30-40% of Parkinson's patients develop these symptoms in addition to the motor symptoms. Overall, Parkinson's patients have an increased risk of developing dementia compared to healthy people. Risk factors include old age at the onset of the disease, pronounced motor symptoms, low level of education and early onset psychoses or depression .

This can lead to cognitive deficits in the following areas:

In addition, apathy , personality changes, hallucinations and delusions can occur.

In Parkinson's dementia, in particular, the executive functions are impaired. People find it difficult to plan and carry out tasks, and their cognitive processing speed is slow. As with the motor symptoms, this is due to the breakdown of nerve cells in subcortical brain regions that are responsible for these functions.

This allows Parkinson's dementia to be differentiated from other forms of dementia such as Alzheimer's , which lead to degradation in cortical brain regions. As a result, memory and language are affected to a greater extent in Alzheimer's disease , which are less affected in Parkinson's disease.

Therapy should be started as early as possible, at the beginning of the disease or, at best, preventively. Since pharmacological treatment has little effect, cognitive training is recommended to delay the onset or worsening of dementia symptoms.  


In the guidelines of the German Society for Neurology (DGN), a complete clinical-neurological examination is initially recommended as a basic diagnosis . In addition, at least one imaging test should be used as part of the diagnosis. Magnetic resonance imaging (MRT) of the brain, cranial computed tomography (CCT) or scintigraphic methods are primarily used for this .

Neurological status: the above symptoms are found on clinical examination. If the rigor is not or not well noticeable, it helps at the same time to actively move the contralateral arm up and down. This unmasks the rigor. In order to distinguish Parkinson's disease from normal pressure hydrocephalus , the patient is allowed to step over an obstacle (ballpoint pen) or a drawn line: with normal pressure hydrocephalus, this is possible despite the same gait pattern, whereas Parkinson's patients cannot.

With the help of scintigraphy of the brain, the loss or reduction of dopamine-producing nerve cells can be shown indirectly. Either positron emission tomography (PET) or single photon emission tomography (SPECT) is used. Under the name DaTSCAN ( dopamine transporter scintigraphy ) a SPECT imaging after injection of is iodine -123-FP-CIT or iodine-123 β-CIT marketed.

Definition of the Parkinson's disease to the Multisystematrophien can MIBG scintigraphy of the heart can be used.

The fact that the symptoms of Parkinson's disease can be positively influenced by L- Dopa (see section Treatment) can also be used diagnostically. In the so-called L- Dopa test, the severity of the symptoms is recorded using a standardized test (usually motor part III of the Unified Parkinson's Disease Rating Scale , UPDRS). This is followed by the administration of a defined amount of L- Dopa, usually 1.5 times the previous medication or 100–200 mg L- Dopa plus a decarboxylase inhibitor . The symptoms are then recorded again. A significant improvement (over 30% of the UPDRS) in the symptoms supports, but does not prove the clinical diagnosis of idiopathic Parkinson's disease, but the dopa sensitivity of the target symptom.

The administration of domperidone is recommended one to two days before the L- dopa test is carried out , since L- dopa can lead to significant nausea and vomiting in previously untreated patients.

The test can also be carried out with the dopamine agonist apomorphine (apomorphine test). The principle is the same, but is intended to make dyskinesia symptoms less likely. It is often used when patients should not primarily receive L- dopa, as is often the case with younger patients (here: under 70 years of age).

Histological examination: A brain biopsy to confirm the diagnosis is out of the question due to the serious side effects and the high risk. However, the deposits of α-synuclein responsible for the disease could also be found in the gastrointestinal tract and in the salivary glands . Histological evidence of these substances could enable a better diagnosis of Parkinson's disease.

CSF examination: In the early stages of Parkinson's disease, there is a decrease in several proteins in the cerebrospinal fluid , including biomarkers characteristic of Alzheimer's disease (e.g. alpha-synuclein and tau proteins ). The waste is still too small and insufficiently researched for diagnosis via the CSF, but connections between the protein concentrations and the course of the disease can be established.

The Scottish nurse Joy Milne can smell Parkinson's disease long before the actual symptoms. This extraordinary olfactory perception is being further researched in several institutes in order to develop early detection tests .


Today there is still no possibility of a causal treatment of Parkinson's syndrome which would consist in preventing or at least halting the progressive degeneration of the nerve cells of the nigrostriatal system. Therefore one has to be content with a treatment of the symptoms, which is increasingly possible, which enables the patient to live an almost unhindered life, at least in the first years (sometimes even decades) of the disease.

As the disease progresses, several drugs are often combined that have to be taken at ever shorter intervals in order to achieve sufficient effectiveness and to avoid fluctuations in effectiveness. If there are still fluctuations in the effect between extreme submobility and hypermobility, one of the three advanced therapy options is used (continuous apomorphine infusion, continuous L-dopa infusion or deep brain stimulation).


Treatment is mainly carried out by administering dopaminergic medication, i.e. drugs that increase the supply of dopamine in the brain, or drugs that replace the lack of dopamine.

The most important drug is L- dopa (levodopa), a precursor of dopamine . This precursor ( prodrug ) - in contrast to dopamine itself - is able to cross the blood-brain barrier . Involuntary movements, so-called dyskinesia , can occur after taking L- Dopa for several years . This is explained by a pulsatile receptor stimulation , since L- Dopa only has an effect time of a few hours. For this reason, treatment with a longer-acting dopamine agonist is usually recommended at the beginning of Parkinson's disease, especially in younger patients . Dopamine agonists mimic the effects of dopamine on the dopamine receptors. With so-called MAO-B inhibitors ( selegiline , rasagiline , safinamide ) the breakdown of dopamine in the brain is slowed down.

Anticholinergics are supposed to counteract the relative predominance of the messenger substance acetylcholine compared to the decreased dopamine. Today, these are rarely prescribed because of their unfavorable side effect profile, especially on cognitive performance. However, they play a role in secondary Parkinson's syndrome induced by neuroleptics . Catechol-O-methyltransferase inhibitors , so-called COMT inhibitors ( entacapone , tolcapone , opicapone ), inhibit the breakdown of the dopamine precursor L- dopa into inactive metabolites . As a result, when taken together with levodopa preparations, they increase the availability of levodopa by 40 to 90 percent and extend its plasma half-life . Entacapone and tolcapone may only be used in conjunction with L- Dopa and a decarboxylase inhibitor. This combination therapy can lead to savings in the dosage of levodopa and thus positively influence the side effect profile. Is also used amantadine , especially in the context of akinetic crisis .

A method for drug setting in the home environment that is currently being developed is ambulatory video-assisted Parkinson's therapy .

L -dopa supplements

L- dopa preparations, of which there are more than 20 different ones in Germany, always contain L- dopa in combination with a decarboxylase inhibitor ( carbidopa or benserazide ), which reduces the breakdown of the L- dopa peripheral ( i.e. in the organism) before it crosses the blood-brain barrier. So you can get by with lower L- dopa doses and with fewer undesirable effects of the preparation outside the brain (such as cardiac arrhythmias, nausea, dry mouth).

A combination preparation consisting of L- dopa, carbidopa and the COMT inhibitor entacapone has existed for a few years . It is indicated in patients in whom fluctuations occur at the end of a dose interval which are not sufficiently stabilized with a combination of L- dopa with only one decarboxylase inhibitor.

Dopamine agonists

In the therapy of Parkinson's disease, in addition to the above-mentioned levodopa, medicinal substances are also used that stimulate dopamine receptors and thus have an effect analogous to dopamine. These include the classic ergot alkaloids = ergot dopamine agonists ( bromocriptine , cabergoline , dihydroergocryptine , lisuride and pergolide ) and the newer selective D 2 receptor agonists = non-ergot dopamine agonists ( apomorphine , piribedil , pramipexole , ropinirole ) and rotigotine . The various preparations differ in their duration of action, in the onset of action, in their galenics and in their side effect profile.

Another theoretical treatment method is amphetamine (also a dopamine agonist ). It leads to an increased release of dopamine into the synaptic cleft and inhibits its re-uptake into the presynaptic neuron. Amphetamines are currently not approved drugs because of their side effects and addictive potential.

COMT inhibitors

COMT inhibitors are drugs that competitively inhibit the dopamine and levodopa-degrading enzyme catechol-O-methyltransferase . COMT inhibitors are always used in combination with levodopa. By inhibiting the breakdown and accumulation of levodopa in the periphery, the uptake of levodopa in the central nervous system increases and thus leads to a desired increase in the dopamine concentration there. Representatives of this group of substances are entacapone ( Comtess , Orion Pharma ), tolcapone ( Tasmar ; Roche ) and opicapone . Tolcapone had been temporarily withdrawn from the market because of severe, but sporadic, liver damage. However, after a new safety assessment by the European Medicines Agency ( EMA ), it was re-approved for the treatment of Parkinson's disease, but with the requirement that the liver values ​​be constantly monitored.

Treatment of advanced Parkinson's disease

Therapeutic area and fluctuations in effect in advanced Parkinson's disease

With the unstoppable progression of the disease, drug treatment has to be adjusted over and over again - by a neurologist or in one of the Parkinson's specialist clinics . In the course of treatment, there is often a multitude of medications that those affected have to take in combination. Nevertheless, complex fluctuations in the effect of the therapy often occur as the disease progresses. The therapeutic window in which the medication works optimally and there is neither over nor under mobility is becoming increasingly narrow.

This is because the number of nerve cells that store dopamine decreases as the disease progresses. It's getting harder and harder to give the right dose at the right time. Are the drugs taken too much (too much dopamine), there is hypermobility , the drugs are too weak (too little dopamine), occurs before the next dose lower mobility again (wearing-off).

Since patients often suffer from slow gastric emptying , tablets often have a delayed effect or fail completely. If the effect finally sets in, it occasionally happens that several tablets that have not yet been digested work simultaneously. The advanced parkinsonian therapy therefore aims at an even supply of active ingredients while bypassing the gastrointestinal tract ( parenteral active ingredient supply). Either continuous pump therapy ( apomorphine pump / L-dopa pump) or deep brain stimulation are used . Apomorphine therapy is the only advanced therapy that does not require surgery.

Apomorphine therapy

Apomorphine is a substance from the group of dopamine agonists with a very strong anti-Parkinson's effect. It can be injected under the skin with an injection pen or infused continuously with a pump. The effects of an apomorphine injection set in within a few minutes (about 8 minutes) and last for about an hour. The therapy can therefore be adjusted very quickly if there are possible side effects. An apomorphine pen is mainly used when patients have few OFF phases per day. The setting for an apomorphine pen is usually done on an outpatient basis.

Apomorphine pen
Apomorphine Pump for Parkinson's Therapy

With continuous apomorphine therapy, the patient wears a mini-pump during the day. Using a thin catheter, a dose of apomorphine adapted to the individual needs of the patient is infused under the skin (e.g. on the abdomen or thigh). The pump can reduce fluctuations in effectiveness, as the active ingredient is released evenly and therefore fewer fluctuations occur than when taking tablets. The setting for an apomorphine pump takes place in a Parkinson's special clinic.

Continuous L-Dopa therapy

In continuous L-Dopa therapy, L-Dopa is delivered directly into the small intestine via a drug pump. For this purpose, a tube (PEG probe) is surgically guided through the abdominal wall into the small intestine and remains there during the entire therapy. L-Dopa is absorbed directly into the body from the small intestine. In this way, the irregular emptying of the stomach, which hinders the taking of tablets, can be avoided and fluctuations in effect can be reduced.

Deep brain stimulation

Stereotaxic device for placing a stimulation electrode

Neurosurgical treatment options have also been used for many years. A method that has been used since the early 1990s is deep brain stimulation, in which a programmable pulse generator (“brain pacemaker”) is used in the patient . It generates electrical impulses and conducts them via thin cables, depending on the localization of the cause of the disease and the corresponding placement of the stimulation electrodes, into the respective basal ganglia, the nucleus subthalamicus , globus pallidus or the anterior thalamus , whereby overactive false impulses can be effectively suppressed there. This procedure can be used for Parkinson's syndromes, but also for dyskinesia and essential tremor if the drug therapy has reached its limits or cannot be used or can only be used to a limited extent for other reasons. A new study has now shown that deep brain stimulation in Parkinson's patients improves driving ability, among other things.

The procedure to place electrodes is a difficult and dangerous stereotactic brain operation that takes around six to twelve hours and requires the most precise planning and control both in advance and during the operation based on radiologically obtained spatial image data and electrically derived neurophysiological measurements. The effect is mostly positive. However, temporary or long-lasting dysarthria (speech motor impairment) and an abnormally increased drive, usually limited to one year, can occur. In rare cases, injuries to the cerebral cortex can also trigger epilepsy . A decisive advantage of the method compared to earlier “ablative” (destructive) procedures, which are no longer used in these clinical pictures today, is its almost complete reversibility .

The implantation of the battery-operated pulse generator itself and its subcutaneous cable connection to the connection contacts of the four-pole platinum - iridium electrodes at their attachment points at the points of passage through the skull is usually only carried out in a second surgical procedure several days after the electrodes have been placed. Depending on its model-dependent size and the physiognomy of the patient concerned, the device is sewn into a specially prepared skin pocket above the chest muscle or in the abdomen. The second procedure is followed by a phase in which the stimulation settings of the pulse generator are individually adapted to the patient's symptoms and programmed in the device. It can easily take several weeks and during this time the above-mentioned side effects (such as dysarthria, dyskinesia, dystonia ) can occur because the patient's brain still has to "get used to" the external stimulation.

The patients then receive a special control device that enables them to independently check the charge status of the battery on a regular basis, to switch the stimulator on and off if necessary and, with some models (after prior professional instruction), to adjust the stimulation settings of the pulse generator within certain preset limit ranges to adapt to the respective situation These control devices work transcutaneously by means of magnetic impulses. Depending on the setting of the pulse generator and its capacity, the primary cells ("batteries") used as energy storage devices keep the device in continuous operation for about three to six years. They are permanently installed in the hermetically encapsulated, inert titanium housing of the device and are therefore practically inseparable from the device. Since they are therefore neither easy to replace nor can they be recharged transcutaneously with the devices previously used, correct functioning of the pulse generator is no longer guaranteed after a corresponding loss of voltage due to the continuous discharge over several years. In order to continue the deep brain stimulation, another short surgical procedure is necessary in which the old device is removed and replaced with a completely new one.

Researchers at Forschungszentrum Jülich and the University of Cologne are working on the development of a brain pacemaker that will not only suppress Parkinson's symptoms, but correct them and allow the brain to function normally again. For this idea they received the Erwin Schrödinger Prize in 2005 .

Gene therapy

Using gene therapy attempts, among other things, on enzymes , the production of dopamine in the basal ganglia to increase, to improve the motor symptoms. Although good results were achieved in the present study from 2014, a placebo effect cannot be ruled out as there is no control group. Oxford BioMedica's therapy consists of injecting genetically modified viruses into the striatum on both sides . This affects tyrosine hydroxylase , DGTP cyclohydrolase, and aromatic L-amino acid decarboxylase to increase dopamine production.

Implantation of fetal brain tissue

The implantation of embryonic stem cells in the brain was able to free rats from Parkinson's tremor, but in 2002 it led to the development of incurable teratomas in five of 19 test animals at Harvard Medical School . The research approach is therefore hardly pursued any further. Therapeutic approaches with further developed stem cells are more promising. This includes the use of neural progenitor cells that have been isolated from fetal tissue. They have been successfully tested on rats and monkeys by scientists from the Rush University Medical Center in Chicago and the Leipzig University Hospital and did not lead to any negative side effects. A double-blind controlled pilot study carried out in the USA on the effectiveness of transplantation of fetal precursor cells of the substantia nigra showed no reliable effect of the transplantation (Annals of Neurology 2003, Olanow et al.). In addition to the complications of the procedure itself, the fluctuations between immobility and overmovement seem to be increasing and becoming more unpredictable.

Complementary treatment procedures

Adequate exercise is important to delay the gradual decrease in mobility that is typical of Parkinson's disease for as long as possible. If the disease is advanced, regular and specially designed physiotherapy is necessary. A speech therapist / speech therapy support is useful when having disease progression speaking (silent and inexact pronunciation, too low and too high voice, rapid speech) and / or swallowing (swallowing usually beginning with liquids, possibly complications such as pneumonia ) worsened. Occupational therapy is supported by aids for everyday life ( buttoning aids , grippers ) and works on spatial perception to improve movement.

Alternative medical treatment methods and prevention

Around 40 to 60% of Parkinson's patients take advantage of alternative medical therapies, usually in addition to drug therapy . Among these, relaxation , meditation , breathing and movement exercises such as taijiquan , qigong , yoga as well as acupuncture and massages are widely used. Some patients use dietary supplements such as vitamins to prevent or treat deficiencies. There are no meaningful clinical studies that have examined the effectiveness of these treatments in terms of quality of life and symptom improvement. When using dietary supplements, there is a possibility of harmful interactions with drug therapy. Caution is particularly advised when taking L- dopa-containing food supplements, for example extracts of the pruritic bean ( Mucuna pruriens ), since the L- dopa content often fluctuates here and, together with a medicinal L- dopa therapy, leads to significant fluctuations in effectiveness can.

According to a study by a working group at the Dresden Max Planck Institute for Molecular Cell Biology and Genetics , the addition of D- lactate (DL, levorotatory lactic acid) and glycolic acid (GA, a fruit acid) makes in vitro cultures of dopamine-producing nerve cells more resistant to degeneration. In the cells that come from the substantia nigra of special laboratory mice, DL and GA maintain the functionality of the mitochondria or restore the functionality of damaged mitochondria. In theory, the regular intake of these substances, for example through fruit yoghurt, which was produced with cultures of “ Lactobacillus bulgaricus ”, could prevent Parkinson's disease or even slow down or even stop Parkinson's in its early stages.

Atypical Parkinson's Syndromes

Classification according to ICD-10
G23 Other degenerative diseases of the basal ganglia
ICD-10 online (WHO version 2019)

There are diseases that are similar to Parkinson's disease and whose cause is also the deterioration of nerve cells in the area of ​​the basal ganglia in the brain . They are called atypical Parkinson’s syndromes or Parkinson’s plus syndromes : People who suffer from these diseases show other symptoms in addition to the Parkinson’s symptoms. The most common diseases in the field of atypical Parkinson's syndromes are as follows:

MSA and LBD belong to the synucleinopathies , CBD and PSP to the tauopathies . Further, an atypical Parkinson syndrome is considered as one of the first neurological symptoms of the leukodystrophies counting Cerebrotendinösen Xanthomatosis (CBX).

The atypical Parkinson's syndromes are comparatively rare. However, there is a high number of unreported cases, precisely because these clinical pictures are rare and patients are often misdiagnosed (as Parkinson's disease, Alzheimer's disease or depression ). In the autopsies turned Lewy body disease infection (Engl. Lewy body disease as the cause of about 50 percent of clinically diagnosed as "typical" Parkinson's Syndrome) out.

See also



  • James Parkinson: A Treatise on the Shaking Palsy / An Essay on the Shaking Palsy. bilingual edition, text from 1817, new edition edited by Jürgen Flügge . Books on Demand , Norderstedt 2009, ISBN 978-3-8370-2207-0 .
  • Reiner Thümler: Parkinson's disease: know more, understand better. Trias, Stuttgart 2006, ISBN 3-8304-3321-2 (popular science).
  • Manfred Gerlach, Heinz Reichmann, Peter Riederer: Parkinson's disease: basics, clinic, therapy. 3. Edition. Springer, Vienna / New York NY 2003, ISBN 3-211-83884-8 .
  • Gerd A. Fuchs, David Emmans, Martin Faller: Parkinson's disease: causes and forms of treatment (= Beck's series , volume 2301: CH Beck knowledge). CH Beck, Munich 2002, ISBN 3-406-48001-2 .
  • Reiner Thümler: Parkinson's Disease: A Guide for Clinic and Practice. Springer, Berlin / Heidelberg / New York NY / Barcelona / Hong Kong / London / Milan / Paris / Tokyo 2002, ISBN 3-540-67471-3 .
  • Thomas Müller: Drug therapy for Parkinson's disease. UNI-MED science, Bremen / London / Boston 2005, ISBN 978-3-89599-864-5 .
  • Wolfgang H. Jost: Therapy of the idiopathic Parkinson's syndrome. 10th edition, UNI-MED science, Bremen / London / Boston 2018, ISBN 978-3-8374-2391-4 .
  • Siegfried Vogel, Reinhard Horowski: Achievement in old age with Parkinson's disease: An essay using the example of Leonardo da Vinci, Wilhelm von Humboldt and Johannes Paul II. Duncker and Humblot, Berlin 2003, ISBN 3-428-11443-4 .
  • Susanne Schäfer : The juvenile and young onset Parkinson's syndromes, special aspects, questions and a challenge for doctor, patient and relatives / Suzie McCoy. Publishing house for science, research and technology, Wermelskirchen 2001, ISBN 3-929095-14-9 .
  • Claudia Trenkwalder: Parkinson's - Understanding and coping with the disease. 2nd Edition. Schattauer, Stuttgart 2014, ISBN 978-3-7945-2975-9 .
  • J. Wiltfang, S. Trost, HJ Hampel: Dementia. Psychiatry, psychosomatics, psychotherapy . Volume 1: General Psychiatry ; Volume 2: Special Psychiatry . 2016, pp. 1–89.


Descriptions from the patient's perspective

  • Jürgen Mette : Everything except Mikado: Life despite Parkinson's. Gerth Medien, Asslar 2013, ISBN 3-86591-762-3 .
  • Wigand Lange: When Parkinson's comes. My experience with an uninvited guest. Gütersloher Verlagshaus, Gütersloh 2007, ISBN 3-579-06954-3 .
  • Helmut Dubiel: Deep in the brain. Kunstmann, Munich 2006, ISBN 3-88897-451-8 .
  • Michael J. Fox : Lucky man. A memoir. Hyperion, New York 2002, ISBN 0-7868-6764-7 . (Autobiography).
    • in German: Comeback. Parkinson's won't win. Ehrenwirth, Bergisch Gladbach 2002, ISBN 3-431-03358-X (from the English by Bernd Rullkötter).
    • as paperback: Comeback. Parkinson's won't win. Bastei Lübbe, Bergisch Gladbach 2004, ISBN 3-404-61551-4 .
  • Reinhard Hinterleitner: My life with Parkinson's disease. Urban and Fischer, Munich 2001, ISBN 3-437-47400-6 .

Advice for relatives

  • Willibald Gerschlager (with Hanne Brachtl, Wolfgang Freitag and Gerald Ganglbauer): Parkinson. Causes, diagnosis, course and forms of therapy; Helping people help themselves. Maudrich, Vienna 2009, 208 pages, ISBN 978-3-85175-907-5 .
  • Angelika Gollbach: Help for self-help. Parkinson's Disease - Advice (not only) for relatives. Maier, Schweinfurt 2007, ISBN 978-3-926300-60-7 .

Journal articles

  • Wolfgang Götz: History of the therapy of Parkinson's disease - almost 200 years no causal therapy . In: Pharmacy in our time , 35 (3), 2006, pp. 190-196.
  • Hansruedi Büeler: Parkinson's Disease - Molecular Mechanisms and Genetics . In: Pharmacy in our time , 35 (3), 2006, pp. 198–203
  • Bernd Riebesehl, Ralph Lipp: Dosage forms in Parkinson's therapy - dosage forms open up new avenues for Parkinson's patients . In: Pharmacy in our time , 35 (3), 2006, pp. 226-23
  • Jan Schindehütte, Walter Paulus, Ahmed Mansouri: Stem Cell Therapy in Parkinson's Disease - Cell Replacement as a Therapeutic Option? In: Pharmacy in our time , 35 (3), 2006, pp. 250-254
  • S. Wenzel, B. Mollenhauer, C. Trenkwalder: Diagnosis and therapy of Parkinson's dementia in clinical practice . In: Der Nervenarzt , 77, 2006, pp. 1439–1443.

Other works (fiction, drama, etc.)

Web links

Commons : Parkinson's Disease  - Collection of Pictures, Videos, and Audio Files



Patient organizations

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