Parkinson's disease (shaking palsy, paralysis agitans)

Parkinson's disease (also called shaking palsy, idiopathic Parkinson's syndrome or Parkinson's disease) is a slowly progressive disease of the brain. It is caused by a progressive loss of dopamine-producing cells in the substantia nigra in the midbrain. As a result, the body can no longer produce sufficient amounts of the neurotransmitter dopamine, leading to motor function (movement) disorders in affected individuals.

The four main symptoms of Parkinson's syndrome are:

• Rigor: muscle stiffness
• Tremor: muscle tremor
• Bradykinesia: the person can only make slow movements - the condition can progress to akinesia (lack of movement)
• Postural instability: lack of stability of upright posture

The disease was first described in 1817 by the British physician James Parkinson. The colloquial name shaking palsy (paralysis agitans) is based on the above-mentioned main symptoms.

In most cases, people do not develop Parkinson's until they are older. The disease most frequently becomes noticeable between the ages of 50 and 60. Only about every tenth person affected is diagnosed before the age of 40. The prevalence of the disease increases with age. Men suffer from Parkinson's more frequently than women.

In the population as a whole, about 100 to 200 people per 100,000 develop Parkinson's disease. It is estimated that one percent of all people over the age of 60 are affected.

Secondary Parkinson's syndrome is comparatively rare. It is caused by damage to the dopamine-producing cells in the brain by toxins such as drugs or carbon monoxide.

Parkinson's disease is caused by a progressive loss of dopamine-producing cells in the brain, resulting in a deficiency of the neurotransmitter. Dopamine is an important component of signal transmission in the brain and is involved in controlling body movement, among other things.

Dopamine is produced in an area in the midbrain called the substantia nigra. In Parkinson's syndrome, this area is destroyed. Only when more than half of the dopamine-producing cells in the substantia nigra have been destroyed do the characteristic symptoms of the disease become noticeable.

Parkinson's syndrome is divided into the following four groups:

• Idiopathic Parkinson's syndrome (IPS): this refers to Parkinson's disease in which there are no identifiable external or genetic causes for the disease. This is the most common type of Parkinson's syndrome, accounting for about 75 percent of cases.
• Familial Parkinson's syndrome: This represents the hereditary, genetic variant of Parkinson's disease. So far, about 10 genes are known to cause familial Parkinson's syndrome.
• Secondary Parkinson's syndrome: Here the cause of the damage to the dopamine-producing cells is known. Examples are the nerve poison MPTP (heroin substitute in the USA in the 1980s), carbon monoxide, manganese or certain brain diseases (AIDS encephalopathy, encephalitis lethargica). Traumatic head injuries ("Boxer Parkinson's") and diseases of the cerebral vessels can also be the cause. In addition, drugs (for example, neuroleptics, lithium, antidepressants, prokinetics) can cause Parkinson's syndrome as a side effect, at least temporarily.
• Dementia of the Lewy body type (DLB): This is a rare form of dementia in which parts of the brain are damaged by deposits of so-called Lewy bodies (small protein bodies). There is an episodic occurrence of disturbances of the memory as well as the motor function.

The symptoms of Parkinson's disease become noticeable only slowly. In many cases, the closest circle of people around the affected person recognise the symptoms at an earlier stage than the patient himself. Often, the symptoms are initially expressed only on one side of the body, before the symptoms spread to the other part of the body.

Parkinson's syndrome manifests itself in the following four main symptoms:

• Bradykinesia (slowing of movement): affected persons can often only perform movements very slowly - this manifests itself, for example, in the fact that Parkinson's patients walk remarkably slowly and can only sit down or stand up with great effort. When walking, the upper body is bent forward and the gait appears shuffling. In addition, fine motor skills deteriorate as the disease progresses, causing the handwriting of those affected to become smaller and smaller over time (called micrographia). Facial expressions are also reduced, and the face appears expressionless. In a late phase of Parkinson's syndrome, akinesia (immobility) may occur.
• Tremor (tremor at rest): The tremor is more noticeable at rest than during movement. In addition, one side of the body is often more affected. The disease name "shaking palsy" is based on the tremor.
• Rigor (muscle stiffness): Since Parkinson's does not cause paralysis of the muscles, muscle strength is maintained. Over time, however, the joints increasingly lose flexibility, which the doctor can determine during the physical examination by passively stretching and bending the affected person's arm above the elbow joint. If rigor is present, this is noticeable in increased resistance.
• Postural instability (disturbance of the position and hold ref lexes): Position reflexes are automatic and involuntary movement patterns that ensure that the body is balanced in movement and does not lose its balance. In Parkinson's disease, these reflexes are impaired, resulting in gait instability and an increased risk of falling.

In most cases, the first symptoms of Parkinson's disease are muscle pain due to general muscle stiffness, which is why patients often consult an orthopaedist first. The following symptoms are further characteristic changes in Parkinson's disease:

• Changes in personality (withdrawal from society, obsessive behavior or perfectionism).
• Monotonous, soft speech
• Difficulty swallowing
• Increased saliva production
• Depression
• Writing disorders (smaller and more difficult to read handwriting than before)

In the later course of Parkinson's disease, so-called dyskinesias may occur. These are involuntary, uncontrollable and excessive movements. Very often, there are also pronounced, rapidly changing fluctuations in mobility. Some affected persons also suffer from a loss of mental capacity, which can lead to dementia.

The most dangerous form of Parkinson's syndrome is the akinetic crisis, which represents an intensive medical emergency situation. In this case, there is a long-lasting complete immobility, in which the affected person is also no longer able to speak and swallow. The seizures can also occur abruptly during phases of good mobility. In most cases, in the advanced course of Parkinson's syndrome, akinetic crises only occur when additional stresses are added, such as discontinuation of medication or febrile illness.

In order to be able to make a diagnosis of Parkinson's syndrome, an anamnesis (taking of the medical history) and a detailed physical and neurological examination are first carried out. The possibility that the complaints are the side effects of certain medications must be ruled out. Important additional information is the time of onset of the disease, whether the affected person has blood relatives with Parkinson's and whether there are digestive or excretory problems as well as disturbances in sexual function.

Imaging techniques such as CT(computed tomography) or MRI(magnetic resonance imaging) can be used to rule out other causes of the symptoms, such as stroke or brain tumours. MRI is used especially in the presence of atypical Parkinson's disease.

In the early stages of the disease, when the symptoms are not yet clearly noticeable, a SPECT (Single Photon Emission Computed Tomography) can be used for a more precise classification of the disease. This involves assessing the metabolic activity of certain nerve cells. IBZM-SPECT and FP-CIT-SPECT can be used to detect disturbances in dopamine metabolism in the brain - however, due to the very high costs, these examination methods are only rarely used.

Particularly in the case of unclear or atypical Parkinson's disease, the diagnosis can be facilitated by the administration of L-dopa (an effective agent in Parkinson's therapy). In addition, the patient's response to drug therapy can subsequently be assessed. Since high concentrations of L-dopa are used in this test and thus more severe side effects can occur than with regular treatment, the test should be carried out in hospital.

The therapy of Parkinson's syndrome is individually adapted to each patient depending on the course of the disease and the symptoms present. Drug treatment, physiotherapy, speech therapy (speech and swallowing training) and surgical interventions are applied and combined depending on the degree of the disease.

Furthermore, the choice of therapy is strongly influenced by the age of the patient. Likewise, occupational and social circumstances have an influence on the Parkinson's patient's need to combat the symptoms as much as possible. It is therefore important that patients and their relatives are involved in the decision-making process as to which therapies should be carried out.

Drug therapy

In order to adequately assess the efficacy of a drug and avoid overdose, Parkinson's therapy involves changing the dose only in small increments. There is a high risk of overdose when trying to suppress all symptoms of the disease with medication.

To date, there is no form of therapy in which the dopamine-producing cells in the brain can be prevented from dying. The current treatment approach is therefore to compensate for the lack of dopamine by means of drug therapy. Since dopamine itself - when administered as a tablet, for example - is unable to penetrate the areas of the brain affected by the disease due to the blood-brain barrier (natural barrier between the bloodstream and the central nervous system), other active substances are used in the therapy:

• Levodopa: Levodopa (L-dopa) is a precursor to dopamine that is able to cross the blood-brain barrier to enter the affected areas of the brain. There, L-dopa is subsequently converted into dopamine and in this way compensates for the lack of dopamine. However, L-dopa is sometimes broken down in the bloodstream before it reaches the brain, causing the drug to lose effectiveness.
  To prevent this premature degradation, L-dopa is combined with other agents. Levodopa itself can cause movement disorders after several years of treatment, making it primarily used in patients after age 70.
• Dopamine agonists: These agents are most commonly used in Parkinson's patients under the age of 70. These are substances that are chemically different from dopamine but have similar effects. They can easily cross the blood-brain barrier and subsequently bind to the same receptors in the nerve cells as dopamine. Unlike L-dopa, there is less risk of developing movement disorders over time. However, the dopamine agonists are less effective.
• MAO-B inhibitors: these drugs increase the amount of dopamine in the brain by inhibiting dopamine breakdown. Normally, after dopamine binds to its receptor, it is broken down by the enzyme MAO-B (mono-amino oxidase-B). MAO-B inhibitors - such as rasagiline or selegiline - now inhibit this enzyme, increasing dopamine concentrations. However, MAO-B inhibitors are less effective than levodopa and than the majority of dopamine agonists.
• NMDA antagonists: NMDA antagonists (N-methyl-D-aspartate antagonists) are drugs that block the action of the neurotransmitter glutamate in the brain. Since blocking the effect of glutamate improves the effectiveness of dopamine, dopamine deficiency can be compensated for somewhat in this way. NMDA antagonists can be used in combination with other medications to help treat Parkinson's disease. The main active ingredient is called amantadine.
• COMT inhibitors: COMT (catechol-O-methyl transferase) is the name given to an enzyme responsible for breaking down L-dopa in the body. COMT inhibitors can therefore be used to prolong the duration of action of L-dopa, as the breakdown of this active substance is inhibited. COMT inhibitors are therefore always administered together with L-dopa.
• Anticholinergics: These agents have no direct effect on the dopamine balance. Their effect is based on inhibiting the overreactive neurotransmitter acetylcholine in Parkinson's syndrome. In this way, a slight improvement in symptoms such as a reduction in tremor and increased saliva production can be achieved. Old people usually do not tolerate anticholinergics, so these agents are primarily used in younger patients.

Deep brain stimulation (tHS)

In deep brain stimulation, a pulse generator (also called a brain pacemaker) is surgically implanted in the Parkinson's patient, which electrically stimulates certain brain areas (subthalamic nucleus, globus pallidus or the anterior thalamus). The stimulation influences the activity of the brain area, which can lead to an improvement in the symptoms of Parkinson's syndrome. Deep brain stimulation is the most common surgical procedure performed for Parkinson's disease.

Using tHS, good results can be achieved against off-phases (phases of complete immobility) and dyskinesias (over-movements). Tremor (trembling at rest) can be improved by electrical stimulation of the thalamus (a specific brain nerve nucleus).

The surgery is performed in only a few, highly specialized centers.

Personal measures

• Seek information from doctors and Parkinson's associations about the disease.
• Regular physical activity can help maintain the best possible state of health. Physiotherapy, occupational therapy and the practice of light endurance sports are highly recommended.
• In many cases, patients with Parkinson's eat and drink too little because they find it difficult to eat due to the motor impairment and tend to avoid going to the toilet. Therefore, special attention should be paid to a balanced diet and adequate fluid intake. Dopamine preparations should not be taken together with a protein-rich diet, as the active substance is then less easily absorbed in the intestine.
• In the case of symptoms such as so-called freezing (the patient can hardly move during this phase), visual stimuli on the floor, such as footprints stuck on the floor, help. Acoustic rhythm stimuli also improve the situation.
• Parkinson's patients should not be urged to hurry, as this prolongs rather than shortens the phase of freezing.

Although Parkinson's syndrome is a steadily progressing disease of the midbrain that is still incurable, effective treatment is possible thanks to modern therapeutic approaches. With the help of active substances such as dopamine agonists or levodopa, a significant increase in life expectancy can be achieved, which is only slightly below the average life expectancy of healthy people of the same age.

However, Parkinson's patients are significantly more likely to require nursing home care due to their physical limitations. Therefore, in addition to drug treatment, physiotherapy, speech therapy (language training) and a conscious diet are also pushed in order to counteract the decline in physical and mental capacities.