Parkinson's: Early Signs, the L-Dopa Principle and On-Off Explained

What is Parkinson's disease?

Parkinson's disease (also Morbus Parkinson) is a chronic disease of the nervous system that progresses slowly. In the brain, nerve cells that produce the messenger dopamine gradually die off. Dopamine is needed so that movements run smoothly and are finely coordinated. When it is lacking, movements become slower, stiffer and less controlled.

Parkinson's cannot be cured but can be treated well. With the right therapy, many people can stay active for a long time. What matters is recognising the right signs early.

Early signs beyond the tremor

Most people immediately think of the tremor with Parkinson's. In fact, however, the disease often begins with quite different, inconspicuous signs, sometimes years before the first movement problems. These include:

• a fading sense of smell, which often goes unnoticed.
• vivid, sometimes violent dreams, in which a person thrashes about or talks in their sleep (a so-called REM sleep behaviour disorder).
• persistent constipation.
• low mood or a depressive mood.
• increasingly small handwriting, an increasingly quiet voice or an arm that swings less when walking.

The typical movement symptoms

The disease shows up above all in four movement symptoms, which typically start on one side of the body at first:

• Slowness (bradykinesia): movements become slower and smaller. This is the core symptom.
• Stiffness (rigidity): the muscles are permanently tense, movements feel stiff.
• Tremor: usually a tremor at rest, often starting in one hand. About one in three of those affected, however, has little or no tremor. More on this: Tremor.
• Balance problems: an unsteady posture and unsteadiness when standing, usually only later in the course.

In addition, there are often non-movement symptoms such as sleep problems, blood pressure swings, pain or low moods.

The cause: a lack of dopamine

In Parkinson's, cells that produce dopamine die off in a particular region of the brain (the black substance, substantia nigra). Why this happens is not yet fully understood. A predisposition and environmental factors probably play a part. In most cases, Parkinson's does not run in families.

The lack of dopamine is the key: it explains the movement symptoms and is at the same time the starting point for treatment.

Diagnosis: how is it determined?

The diagnosis is usually made by a neurologist, above all based on the typical symptoms and a physical examination. Helpful are:

• checking whether the movement symptoms respond to dopamine-acting medicines.
• a smell test, as an impaired sense of smell can support the diagnosis.
• in unclear cases, special examinations, such as imaging of the dopamine system (DaTSCAN) or a sleep study.
• magnetic resonance imaging (MRI) to rule out other causes.

There is no simple blood test that proves Parkinson's.

Treatment: the principle of L-dopa

The most effective treatment replaces the missing messenger. The problem with this: dopamine itself cannot pass from the blood into the brain. But its precursor L-dopa (levodopa) can. In the brain, L-dopa is then converted into dopamine and makes up for the lack.

So that as much of it as possible reaches the brain and fewer side effects arise, L-dopa is always combined with a second active ingredient (carbidopa or benserazide), which slows down its breakdown in the rest of the body. L-dopa is often the first choice, especially in older people. More on this: Levodopa.

In the early phase, L-dopa usually works evenly throughout the day. Over time this changes, and this is exactly where on-off comes into play.

On and off: why timing matters

After some years of treatment, L-dopa often no longer works so evenly. The reason: the further the disease progresses, the less the brain can store dopamine. The effect then follows the rhythm of taking the tablet more closely. Two states are distinguished:

• On: the medicine is working, movements succeed well. With a very strong effect, involuntary excess movements can sometimes occur.
• Off: the effect wears off, mobility gets worse. Stiffness, slowness and tremor return.

When the effect wears off towards the end of each dosing interval, this is called motor fluctuations (wearing-off). Sometimes on and off also switch quite suddenly.

Further building blocks of treatment

Besides L-dopa, there are further building blocks that are used alone or in combination:

• dopamine agonists (for example pramipexole or ropinirole, also as a patch): they mimic the effect of dopamine and are often used in younger people.
• MAO-B inhibitors and COMT inhibitors: they prolong the effect of the existing dopamine or of L-dopa.
• in advanced disease: deep brain stimulation (a pacemaker in the brain) or medication pumps.

At least as important are non-drug building blocks: physiotherapy, occupational therapy and speech therapy, as well as regular exercise. Strength, balance and endurance training should be part of it from the start and can have a positive effect on the course.

When to see a doctor, and an important safety note

See a doctor, ideally a neurologist, when several of the signs mentioned occur in you, especially a slowness together with stiffness or tremor. Also, when motor fluctuations, falls, swallowing problems or confusion occur with a known Parkinson's disease, the treatment should be adjusted.

Keep your treatment in rhythm with brite

With Parkinson's in particular, the exact timing of intake decides your mobility. brite helps you stay on time and keep the overview.

• On-time reminders: even with several precisely timed doses a day.
• Progress diary: record on and off phases, helpful for your next appointment.
• Interaction check: see at a glance whether your medicines work well together.
• Medication plan: always up to date and ready for the next appointment.

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