Parkinson's Disease

What happens in Parkinson's disease

Dopamine is a chemical messenger that helps the brain control smooth, coordinated movement. In Parkinson's, dopamine-producing neurons in the substantia nigra degenerate. By the time movement symptoms appear, a large share of these cells has already been lost.

Inside affected neurons, a protein called alpha-synuclein clumps into deposits called Lewy bodies. These appear in other parts of the nervous system too, including the gut and the brain areas controlling smell, sleep and mood, which explains non-motor symptoms.

Early signs of Parkinson's

Early signs are often subtle and one-sided:

• a slight tremor in a finger, thumb or hand at rest ("pill-rolling")
• smaller, cramped handwriting (micrographia)
• reduced arm swing when walking
• stiffness or aching in a shoulder or hip
• softer or monotone voice
• reduced facial expression ("masked face")
• slowness with dressing or getting up from a chair

Non-motor symptoms that can come years earlier:

• loss of smell (anosmia)
• REM sleep behavior disorder: acting out vivid dreams
• constipation
• depression and anxiety

Symptoms

Motor symptoms

• bradykinesia: slowness and reduced size of movements, the core feature
• resting tremor: present in most, but not all, people
• rigidity: stiffness of the limbs, neck or trunk
• postural instability: balance problems and falls, usually later
• gait changes: shuffling, short steps, freezing (feet feel stuck), stooped posture
• swallowing problems and drooling in later stages

Non-motor symptoms

• depression, anxiety and apathy
• sleep disturbances and daytime sleepiness
• orthostatic hypotension: dizziness on standing
• constipation, bladder urgency, sexual problems
• pain, fatigue
• cognitive changes and, in many people after years, dementia
• hallucinations, often related to medicines

Causes and risk factors

• age: the biggest risk factor
• sex: men are affected about 1.5 times more often
• genetics: about 10 to 15 percent have a genetic contribution (such as LRRK2 or GBA gene variants)
• environmental exposures: some pesticides and solvents (such as trichloroethylene), repeated head injury
• coffee drinking and smoking are associated with lower risk, but smoking is not recommended

Parkinson's vs other tremors and parkinsonism

Diagnosis

Parkinson's is diagnosed clinically by a neurologist, ideally a movement disorder specialist:

• history and neurological exam showing slowness plus tremor or rigidity
• a good response to levodopa supports the diagnosis
• DaT scan: shows reduced dopamine transporter, helping separate Parkinson's from essential tremor
• alpha-synuclein tests: skin biopsy and spinal fluid seed amplification assays can detect abnormal alpha-synuclein
• MRI to rule out other causes

Stages

The Hoehn and Yahr scale is commonly used:

1. symptoms on one side, minimal disability
2. symptoms on both sides, balance intact
3. balance problems, but still independent
4. severe disability, can walk or stand with help
5. wheelchair- or bed-bound without help

Progression varies widely; many people remain independent for many years.

Treatment

Medicines

• Levodopa (with carbidopa): the most effective treatment for motor symptoms. Over years, effects can wear off between doses and involuntary movements (dyskinesias) can appear.
• Dopamine agonists (pramipexole, ropinirole, rotigotine patch): can cause sleepiness and impulse control problems.
• MAO-B inhibitors (rasagiline, selegiline, safinamide) and COMT inhibitors (entacapone, opicapone) extend levodopa's effect.
• Amantadine: reduces dyskinesia.
• Rescue therapies: inhaled or under-the-tongue levodopa, apomorphine for "off" periods.
• Continuous delivery: levodopa gel through a feeding tube, or under-the-skin infusions, for advanced disease.

Surgery

Deep brain stimulation (DBS): electrodes placed in the brain, connected to a pacemaker-like device, reduce motor fluctuations, tremor and dyskinesia in selected people. Focused ultrasound can treat tremor on one side.

Exercise and therapies

• regular aerobic exercise, strength and balance training may slow functional decline
• physical therapy for gait, balance and fall prevention
• occupational therapy for daily tasks
• speech therapy (such as LSVT LOUD) for voice and swallowing

Treating non-motor symptoms

Antidepressants, constipation management, treatments for low blood pressure, sleep therapies, and medicines for hallucinations or dementia.

Living with Parkinson's

• take medicines on time; in hospital, make sure staff give doses on schedule
• avoid medicines that block dopamine, such as haloperidol and metoclopramide
• make the home safer to reduce falls
• stay socially and physically active
• plan ahead for care needs

Frequently asked questions

What are the early signs of Parkinson's disease?

Early signs include a slight resting tremor on one side, smaller handwriting, reduced arm swing, stiffness, a softer voice and reduced facial expression. Loss of smell, constipation and acting out dreams can appear years before movement symptoms.

What causes Parkinson's disease?

Parkinson's is caused by the loss of dopamine-producing nerve cells, linked to clumping of the protein alpha-synuclein. Age, genetics and environmental exposures such as certain pesticides contribute, but most cases have no single identifiable cause.

Is Parkinson's disease fatal?

Parkinson's itself is not usually directly fatal, but complications in advanced stages, such as falls, swallowing problems and pneumonia, can shorten life. Many people live for decades after diagnosis with good treatment.

Can Parkinson's disease be cured?

There is no cure yet. Medicines, exercise, therapies and deep brain stimulation can control symptoms effectively for many years. Research into treatments that slow progression is ongoing.

What is the difference between Parkinson's and essential tremor?

Parkinson's tremor occurs mainly at rest, often starts on one side and comes with slowness and stiffness. Essential tremor occurs during action, such as holding a cup, usually affects both hands, may involve the head or voice, and has no slowness.