Parkinson's disease: an animated, cited guide

This page needs JavaScript for its animations. The outline and key answers are below, and every claim in the full version carries a numbered citation.

Not medical advice. Parkinson's Companion is an educational synthesis of published literature. It does not replace a clinician.

What is in it

What Parkinson's is Parkinsonism versus Parkinson's disease, who it affects, the numbers.
The dopamine pathway Substantia nigra to striatum, the go and brake loops, and what losing dopamine does.
Alpha-synuclein and Lewy bodies From a small synaptic protein to a Lewy body, and how it may spread.
How it spreads: Braak stages Six stages from the brainstem to the cortex, and the body-first debate.
Genes and inheritance LRRK2, GBA1, SNCA and parkin, founder populations, and what a test means.
Before the tremor Dream enactment, smell, constipation and the prodromal criteria.
Stages and symptoms Hoehn and Yahr, motor and non-motor symptoms, and how fast it moves.
Diagnosis and the MDS criteria The clinical criteria as a calculator, DaT scans and synuclein tests.
The differential Essential tremor, drug-induced parkinsonism, MSA, PSP and Lewy body dementia.
Levodopa and carbidopa From the pill to the striatum, step by step.
Levodopa over time Wearing-off, dyskinesia, the narrowing window and what smooths it.
The other medicines Agonists, MAO-B and COMT inhibitors, amantadine and the order of use.
Deep-brain stimulation Targets, the stimulation field, the beta rhythm and what the trials found.
Beyond movement Mood, hallucinations, dementia, sleep and blood pressure.
Risk and protection Pesticides, solvents, head injury, smoking, coffee and exercise.
Living with Parkinson's Exercise, therapy, falls, speech, work, caregiving and the end of life.
Nursing care Medicines on time, drugs to avoid, swallowing, assessment, documentation.
Toward a cure Synuclein antibodies, GLP-1 drugs, LRRK2 and GBA1, cells and genes.
History and people From James Parkinson's 1817 essay to the synuclein test.
Flashcards and mnemonics Flip cards by topic.
Quiz Questions with explanations.
Glossary Every term, searchable.
Sources Every reference behind the guide.

Part 2 · Course and diagnosis

Diagnosis and the MDS criteria

There is still no single test for Parkinson's. The diagnosis is clinical: a specialist confirms parkinsonism, looks for anything that points elsewhere, and weighs the warning signs against the supportive ones. Tick the features below, or load an example, and the 2015 MDS criteria give their verdict. Then see what a scan or a synuclein test adds.

The MDS clinical diagnostic criteria were built for research, but may serve as a general guide in clinical practice. ^112,213 NICE guidance in the UK, which predates them, still bases diagnosis on the UK Brain Bank criteria and advises referring people with suspected Parkinson's "quickly and untreated" to a specialist. ²⁴¹ This calculator is a teaching tool, not a diagnosis.

Load an example

How well it works

Walk the case through the four steps

The same case, one gate at a time. The marker stops at the first gate it fails.

Steps

The steps and rules follow the 2015 MDS criteria. ^213,288 Change the ticks above and replay.

What a positive scan or synuclein test really means

Teaching toolPick a test (its sensitivity and specificity) and how likely the condition is before testing. The grid sorts 1,000 people by their true status and their result. The arithmetic is exact; whether the inputs fit any one person is not.

Test

Setting

Sensitivity88% Specificity96% Pre-test probability42%

Reveal

Filled circle: true positive. Ring: false negative. Square: false positive. Small dot: true negative. Teaching tool, not a diagnostic calculator.

The test toolbox

FDA approved

DaT-SPECT (ioflupane)

Approved in 2011, with suspected dementia with Lewy bodies added in 2022, as "an adjunct to other diagnostic evaluations". It shows loss of dopamine terminals, but PD, MSA and PSP all have that, and the scan "was not designed to distinguish among the conditions". It changed management in 54% and the diagnosis in 31% of people with suspected parkinsonism. NICE suggests considering it for tremor when essential tremor cannot be told from parkinsonism clinically. ^27,99,241

Debated

When the scan is normal (SWEDD)

In the ELLDOPA trial, 19 of 142 imaged people with clinically diagnosed early PD (about 13%) had no dopaminergic deficit. Under MDS 2015 a normal scan is an absolute exclusion, so they cannot count as PD. In PPMI, synuclein SAA was positive in 9% of these people against 4% of controls. Some experts object that early scans can be of low quality. ^97,213,332

Established

Cardiac MIBG

Against other neurodegenerative parkinsonism, the delayed heart-to-mediastinum ratio gave 89.7% sensitivity and 82.6% specificity; in early PD, 94.1% and 80.2%. Cardiac sympathetic denervation on MIBG is one of the MDS supportive criteria, alongside smell loss, but no autopsy series in a 2025 review reported it, a sign of limited availability. ^112,258,288

Established

MRI signs

Loss of the nigrosome-1 "swallow tail": sensitivity 0.94, specificity 0.90, but only against healthy adults. ⁵⁴
Hummingbird sign for PSP: specificity 99.5%, sensitivity only 51.6%. ²³⁴
Hot-cross-bun sign and putaminal diffusivity (90% sensitivity, 93% specificity against PD) are MRI markers in the 2022 MSA criteria. ³⁷³
NICE advises against structural MRI to diagnose PD itself. ²⁴¹

Research use

Synuclein seed amplification (SAA)

In PPMI spinal fluid, SAA found PD with 87.7% sensitivity and 96.3% specificity against controls. Positivity was 98.6% in sporadic PD with smell loss, 78.3% without it, and 67.5% in LRRK2 PD. The FDA has endorsed it for enriching clinical trials, which is not a diagnostic approval; access is "mostly limited to research studies". ^112,332,344

Early evidence

Skin biopsy

Phosphorylated synuclein in skin was found in 92.7% of PD, 98.2% of MSA, 96.0% of DLB, 100% of pure autonomic failure and 3.3% of controls. The authors say it still needs validation "in unselected clinical populations". The commercial test is not FDA-approved as a diagnostic for PD. ^124,153

Advised against

Levodopa and apomorphine challenges

Sensitivity for established PD was 0.86 for apomorphine, 0.75 for an acute levodopa test and 0.91 for chronic levodopa therapy. The review concluded that the acute tests add nothing to chronic treatment and cause adverse events, and NICE advises against them. ^63,241

Established

How often the clinical diagnosis is right

In 100 brains of people diagnosed with PD by neurologists in 1992, only 76 had PD. A meta-analysis put the accuracy of clinical diagnosis at 80.6%, and it had not improved over 25 years. In a London community study, at least 15% of people with a PD diagnosis did not meet strict criteria. ^157,309,320

Should Parkinson's be defined by biology?

In 2024 two groups proposed research definitions built on the synuclein test, and the Movement Disorder Society answered with a statement of caution. Pick a person to see how each framework would describe them. Disputed

Person

Exam hookMDS 2015: parkinsonism first (bradykinesia plus rest tremor and/or rigidity), then 9 absolute exclusions, then 10 red flags counterbalanced by 4 supportive criteria. Established = no red flags and at least 2 supportive criteria. A normal DaT scan is an absolute exclusion; a clear and dramatic levodopa response and levodopa-induced dyskinesia are supportive. ^213,288