101 | Diagnosis of Parkinson’s

Clinical Evaluation & Diagnostic Investigations for Parkinson’s

One of the most challenging aspects of diagnosing Parkinson’s is that there is no single, definitive test, like a routine blood test or a standard brain scan, that can instantly confirm the condition. Diagnosis is primarily clinical, meaning it is based on a detailed medical history, a thorough physical examination, and observed symptoms. For people living with young onset Parkinson’s (YOP), where symptoms typically begin before the age of 50, getting an accurate diagnosis can be especially complex and lengthy, as parkinsonism is less expected in younger age groups.

Diagnosing Parkinson’s begins with recognising its early symptoms. Because the condition develops gradually as dopamine-producing cells in the brain are lost, sometimes over decades, these signs may be subtle at first. The core motor symptoms may include:

• Tremors (shaking): This is often the most recognisable sign, typically starting in one hand, fingers, or arm. In Parkinson’s, this is usually a “resting tremor,” meaning it occurs when the limb is fully relaxed and supported, and it often improves when you deliberately move the hand. However, this only occurs in around 70% of people living with Parkinson’s.
• Slowed body movements (bradykinesia): This refers to a general slowness of movement and a decrease in the size or speed of actions. It can make everyday tasks difficult, causing a person to take shorter, shuffling steps or causing a noticeable reduction in arm swing on one side of the body while walking.
• Muscle stiffness (rigidity): Patients often experience an increased, uniform resistance to passive joint movement. This stiffness can happen in the limbs, neck, or trunk, sometimes causing painful muscle cramps (dystonia), which are particularly common as an early symptom in young onset Parkinson’s.
• Balance & coordination issues: Also known as postural instability, this can lead to unsteadiness and an increased risk of falls. While severe balance problems usually appear as the condition progresses, subtle coordination difficulties can be present early on.
• Changes in handwriting: A classic early sign is “micrographia,” where a person’s handwriting becomes unusually small, cramped, and tightly spaced.
• Speech and facial expression changes: Parkinson’s can cause “hypomimia,” which is a reduction in facial expressions leading to a mask-like appearance. It can also cause changes in the voice, making it sound soft, breathy, or lacking in normal emotional tone (monotone). You may also notice that you blink less.

The Hidden Signs

Non-Motor & Prodromal Symptoms

While the motor symptoms are the most visible, researchers now call Parkinson’s is a whole-body condition. Many ipeople experience non-motor symptoms years, or even decades, before the physical movement issues begin. This early phase is known as the “prodromal” stage. Recognising these hidden signs can be crucial for an early evaluation.

One of the most common early warning signs is a loss of the sense of smell (hyposmia). Another very frequent early symptom is constipation, which can occur because the condition affects the nerves in the gut long before it heavily impacts the brain’s movement centres. Sleep disturbances are also highly significant, particularly Rapid Eye Movement (REM) sleep behaviour disorder (RBD). In RBD, the normal muscle paralysis that occurs during dreaming is lost, causing people to physically act out their dreams by shouting, thrashing, or falling out of bed. Furthermore, mood changes, such as new-onset or unexplained anxiety, depression, and apathy, frequently appear before motor symptoms and can heavily impact a person’s quality of life.

What Happens During Diagnosis?

When you visit a neurologist, the clinical evaluation is the most critical part of the process. Although there is no single test to perfectly confirm Parkinson’s, a series of investigations and structured observations can strongly support the diagnosis or rule out other conditions.

To systematically assess your condition, the neurologist will often use a standardised tool called the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). During the physical examination, the neurologist will assess:

• Reflexes & muscle tone: The doctor will gently move your arms, legs, and neck to check for “lead-pipe” or “cogwheel” rigidity. Cogwheel rigidity feels like a ratchet-like resistance when the limb is moved.
• Coordination & balance: To test your balance, the doctor may perform a “pull test,” where they stand behind you and give your shoulders a sudden, gentle pull backward to see how well you recover your footing. A normal response is a rapid recovery in one or two steps.
• Hand & finger movements: You will be asked to perform repetitive tasks, such as tapping your index finger and thumb together as fast and as wide as you can for several seconds. The doctor is looking for bradykinesia, specifically, whether the tapping slows down or the movements become smaller as you continue. You may also be asked to open and close your hands or tap your toes.
• Walking & posture: The neurologist will watch you walk down a hallway to observe your stride length, the speed of your walking, your posture (looking for a stooped forward lean), and whether both your arms swing naturally at your sides.

Another key part of the diagnostic process is evaluating your response to dopaminergic medication, most commonly levodopa. Because Parkinson’s is caused by a lack of dopamine, taking a medication that replaces dopamine should significantly improve your motor symptoms. A clear, dramatic, and sustained improvement in your symptoms after starting levodopa strongly supports a diagnosis of Parkinson’s.

Formal Diagnostic Criteria

To ensure accuracy, specialists rely on the Movement Disorder Society (MDS) clinical diagnostic criteria. According to these rules, a patient must first have “Parkinsonism,” which is strictly defined as having bradykinesia combined with either a resting tremor, muscle rigidity, or both.

Once Parkinsonism is established, the doctor looks for “supportive criteria” (positive signs like a great response to levodopa or a classic pill-rolling tremor) and checks for “red flags”. Red flags are unusual symptoms that suggest the problem might not be standard Parkinson’s. For example, if a patient requires a wheelchair within the first five years, suffers from early and severe falls, or has early severe dementia, these are red flags. The doctor will also check for “absolute exclusion criteria,” symptoms that completely rule out Parkinson’s, such as the symptoms being caused by a specific dopamine-blocking drug (drug-induced Parkinsonism) or brain scans showing significant vascular strokes. By balancing these supportive features against any red flags, doctors can classify the diagnosis as either “clinically established” or “clinically probable” Parkinson’s.

Ruling Out Other Conditions

It is vital to confirm that the symptoms are not caused by other neurological disorders that mimic Parkinson’s. These mimics are broadly categorised as “atypical Parkinsonism” or “secondary Parkinsonism”.

• Atypical Parkinsonism (Parkinson-Plus Syndromes): These are neurodegenerative conditions that progress faster than typical Parkinson’s and usually do not respond well to levodopa medication:
  • Progressive Supranuclear Palsy (PSP), which is characterised by early backward falls and difficulty looking downwards
  • Multiple System Atrophy (MSA), which features severe early autonomic problems like urinary incontinence and severe blood pressure drops
  • Corticobasal Degeneration (CBD), which presents with marked asymmetry, where one limb may become rigid, apraxic, and sometimes act seemingly on its own (alien limb phenomenon).
• Secondary Parkinsonism: This includes Drug-Induced Parkinsonism, caused by certain anti-nausea or psychiatric medications that block dopamine receptors. It also includes Vascular Parkinsonism, which is caused by multiple small strokes in the brain and typically affects the legs and walking much more than the arms.
• Essential Tremor: Essential Tremor (ET), or familial tremor, is a very common condition that causes shaking. Unlike Parkinson’s, the tremor usually happens when the hands are in action (like holding a cup or writing), rather than when they are at rest. It tends to run in families.

Additional Tests & Investigations

While the diagnosis relies on the neurologist’s clinical expertise, the neurologist may recommend additional tests to support the diagnosis, clear up uncertainty, or definitively rule out the other conditions mentioned above. These might include:

1. DaTscan (Dopamine Transporter Scan)

A DaTscan is a specialised imaging test that measures dopamine activity in the brain. During this procedure, a small amount of a safe radioactive tracer is injected into your bloodstream. This tracer specifically binds to dopamine transporters in the striatum, a deep part of the brain responsible for movement. A few hours later, a SPECT (Single-Photon Emission Computed Tomography) scanner takes pictures of your brain.

In a healthy brain, the scan lights up brightly, showing a healthy abundance of dopamine nerve terminals. In a person with Parkinson’s disease, the scan will show a dimmer, asymmetrical, or “comma-shaped” signal, indicating that dopamine-producing cells have been lost. A DaTscan is highly useful for differentiating Parkinson’s disease from essential tremor or drug-induced Parkinsonism, because the scan remains completely normal in those conditions. However, it cannot easily differentiate between typical Parkinson’s and atypical syndromes like MSA or PSP, because all of these conditions involve dopamine cell loss.

2. MRI or CT Scans

Standard Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scans of the brain are typically normal in people with Parkinson’s. Therefore, these scans are not used to positively diagnose Parkinson’s. Instead, they help rule out other neurological disorders. An MRI can clearly show if a patient’s symptoms are being caused by a brain tumour, a series of small strokes (vascular Parkinsonism), or a condition called normal pressure hydrocephalus, which is an abnormal buildup of spinal fluid in the brain’s cavities.

Recently, advanced MRI techniques have been developed that can look closely at the substantia nigra (the specific area of the brain where dopamine cells die in Parkinson’s). Specialised scans looking at “neuromelanin” (a dark pigment inside dopamine cells) or a specific structure called “nigrosome-1” can actually show the physical loss of these cells. A healthy brain shows a distinct “swallow tail” shape in this region, which disappears in Parkinson’s. While highly promising, these advanced MRI techniques are not yet standard in all routine clinical practices.

3. Blood Tests & Genetic Testing

Standard blood tests cannot currently diagnose Parkinson’s, but they are frequently used to exclude other medical conditions that may mimic Parkinson’s symptoms. For example, in patients younger than 40, doctors will always order a blood test to check ceruloplasmin levels to rule out Wilson’s disease, a rare, treatable genetic disorder that causes copper to build up in the brain and liver, leading to severe movement issues.

Genetic testing is becoming an increasingly important part of the diagnostic puzzle, particularly for people with Young Onset Parkinson’s (YOP). While most Parkinson’s cases are “sporadic” (meaning they happen randomly without a clear family link), a genetic cause is much more likely when symptoms begin at a young age. Testing can look for specific mutations in genes such as PRKN, PINK1, SNCA, and LRRK2. Identifying a genetic mutation can provide a definitive explanation for the disease, offer insights into how the disease might progress, and inform family planning. Furthermore, knowing your genetic status can be a crucial gateway to participating in targeted clinical trials, as new therapies are currently being developed that specifically aim to correct the biological pathways disrupted by these exact gene mutations.

4. The Future of Diagnosis

Alpha-Synuclein Biomarker Tests

For decades, researchers have searched for a specific biological marker for Parkinson’s. We now know that the root cause of Parkinson’s is the abnormal clumping of a protein called alpha-synuclein, which forms toxic structures called Lewy bodies in the nervous system. Until recently, these toxic clumps could only be confirmed by examining the brain after a person had passed away.

Seed Amplification Assays (SAA)

Recently developed, these tests can detect microscopic amounts of misfolded alpha-synuclein in living patients. Currently, this is done in two main ways:

• Cerebrospinal Fluid (CSF) Testing: By performing a lumbar puncture (spinal tap), doctors can collect spinal fluid. The SAA test can detect the toxic alpha-synuclein seeds in this fluid with incredibly high accuracy (around 90-95%).
• Skin Biopsies: Because Parkinson’s affects the entire nervous system, abnormal alpha-synuclein also builds up in the tiny nerve fibres of the skin. Doctors can take three small, simple skin punch biopsies (usually from the neck, thigh, and lower leg) and use special dyes or SAA testing to identify the toxic protein. This minimally invasive test is showing exceptional promise, correctly identifying Parkinson’s in over 92% of cases and strongly differentiating it from healthy individuals.

These alpha-synuclein tests represent a massive leap forward. They are so accurate that medical societies have recently proposed a new biological definition for the disease, termed “Neuronal alpha-Synuclein Disease” (NSD). While currently used mostly in research and specialised clinics, these tests are paving the way for a future where Parkinson’s can be diagnosed objectively with a lab test, potentially even before the very first physical tremor appears.

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