Shortcuts to topics dealt with in this article:
What is Parkinson's disease?
Causes
Symptoms
Diagnosis
Treatment
Levodopa
Wearing-off phenomenon
www.wearingoff.com
Future treatments
Parkinson’s disease is a progressive neurological disorder that affects movements such as walking and writing. James Parkinson first described the disease in 1817, and it was named after him. Since then many effective treatments have been developed, which help to treat the symptoms of Parkinson’s disease.
Parkinson’s disease usually affects people over the age of 50 years, but younger people can also develop the disease. When Parkinson’s disease occurs in people aged between 21 and 40 years, it is called ‘young onset Parkinson’s disease’. 5 to 10% of patients fall into this group. Parkinson’s disease affects about 4 million people globally. The mean age of onset is approximately 60 years.
Normal movement is dependent on appropriate production of a chemical messenger or ´neurotransmitter´ called dopamine by cells in a an area of the brain called substantia nigra, Parkinson’s disease occurs when the cells in this part of the brain begin to lose their ability to produce this ‘chemical messenger'. When most of the dopamine-producing cells have stopped working, the symptoms of Parkinson’s disease start to appear. The reason why these cells stop working is not yet known. The symptoms of Parkinson’s disease become gradually evident, when about sixty to eighty percent of the dopamine-producing cells in the brain are lost.
The three main symptoms of Parkinson’s disease are tremor, muscular stiffness and slowness of movement, or bradykinesia.
Tremor
Resting tremor is the most common symptom of Parkinson’s disease, affecting almost 70% of patients. Tremor usually begins in one hand or arm. It typically occurs when the affected part of the body is resting, and it decreases or even disappears when the affected part is being used.
Muscular rigidity or stiffness
Stiffness can affect many of the usual activities that we do daily, that we take for granted. For example, people can find it difficult to turn around, get out of a chair and roll over in bed. It can also be difficult to carry out tasks that require fine finger movements such as opening a door with a set of keys, writing with a pen or even sorting through loose change when out shopping. Some people also develop a stooped posture. And some patients’ face becomes stiff. This can make facial expressions such as smiling more difficult.
Slowness of movement
Slowness of movement, the different forms of which are called bradykinesia, hypokinesia and akinesia in medical terms, encompasses slowness of initiation of voluntary movements as well as progressive reduction of speed and amplitude of motor actions. This difficulty with movement is often described as the most disabling feature of Parkinson’s disease. ‘Freezing’ means a momentary inability to move one’s feet during walking. Patients feel as if their feet were stuck to the floor. Tricks such as stepping over an object and attempting to march rather than walk may be helpful. Freezing may also be alleviated by following a visual cue or a rhythmic sound.
Other common signs include:
- shuffling gait (walking) that is characterized by short steps, with feet barely leaving the ground
- small handwriting
- reduced degree of facial expressions, also called hypomimia
- at a later stage of the disease, impaired balance
- hypophonic speech, meaning soft, monotonic and hoarse speech quality.
Non-motor symptoms
Although Parkinson’s disease is primarily regarded as a movement disorder, also other, non-motor symptoms may be experienced by patients at later stages of the disease. These are often considered as being even more troublesome than the motor symptoms. Non-motor symptoms may include:
- Disorders of sleep including inability to fall asleep, vivid dreams and numerous night time awakenings.
- Excessive day time sleepiness may significantly interfere with the normal activities of daily living.
- Depression, along with anxiety, is the most commonly encountered mood disorder in Parkinson’s disease, affecting 40 to 50% of patients.
- Dysfunction of the autonomic nerve system is an important cause of certain non-motor symptoms such as excessive salivation, light-headedness upon standing, constipation, urinary frequency and the need to get up during the night in order to urinate (nocturia), thus interrupting sleep.
- Cognitive decline or dementia and hallucinations may develop at later stages of the disease
The symptoms usually begin very gradually and develop slowly. Each person with Parkinson’s disease has a unique collection of symptoms and also responds to the treatment uniquely.
The diagnosis of Parkinson’s disease is made in a clinical evaluation. There are currently no laboratory tests that could confirm the diagnosis. PET (Positron emission tomography) and SPECT (Single photon emission computerized tomography) scans give further support to the clinical diagnosis in some cases. It is important for the doctor to exclude any possibility of another disease behind the signs and symptoms resembling Parkinson’s disease.
Currently, there is no cure for Parkinson's disease, but there is a range of treatments available to help control its symptoms and so make the patient’s daily life easier. Helping to control the symptoms of the condition can help maintain the quality of life of not only the patient but also his or her family members and caregivers.
The scientific discovery that Parkinson’s disease is associated with lower than normal levels of neurotransmitter dopamine in the brain has led the way to current medicinal treatment strategies. Broadly speaking they either replenish dopamine levels or mimic the action of dopamine in the brain (figure). Dopamine levels are replenished with various medicines based on levodopa, which is converted to dopamine in the brain, as well as with medicines called MAO-B inhibitors, which inhibit dopamine from breaking down in the brain. Means of mimicing the action of dopamine comprise medicines called dopamine agonists.
The landmark discovery of the fact that levodopa improves the symptoms of Parkinson’s disease came as early as in the late 1960s.
Soon after the discovery of levodopa it was learnt that when given alone, levodopa gradually lost its effect due to rapid breakdown in the body. Today’s levodopa treatments are enhanced with additional compounds which block the action of the two major enzymes involved in the levodopa breakdown, DDC (dopa-decarboxylase) and COMT (catechol-O-methyltransferase).
Regardless of good short-term tolerability and efficacy, the use of levodopa is complicated by long-term problems, particularly the so-called wearing-off phenomenon and involuntary movements called dyskinesias. The development of these long-term complications is thought to be due to a combination of disease progression and the rapid metabolisation of levodopa. Symptoms of wearing-off may be addressed by using a levodopa preparation with dual enzyme inhibition or adding a dopamine agonist or an MAO-B inhibitor into the treatment regimen. The two latter options are used also for early Parkinson’s disease as mono-therapy.
Our wearingoff.com website is a comprehensive, simple and effective source of information for patients, their families and caregivers for recognising wearing-off appropriately and coping with the symptoms.
There is no cure available for Parkinson’s disease currently, and therapies that would unquestionably delay disease progression are still awaited. Current clinical research focuses on the development of treatments ameliorating motor complications. There are, however, major development projects in the field of non-drug cell, tissue and gene therapies as well as neuroprotective pharmaceutical agents.
Updated
Sep 21st 2010