Parkinson’s vs. Atypical Parkinson’s: What’s the Difference?

Most people have heard of Parkinson’s disease, but far fewer are aware of the broader family of conditions known as parkinsonism, a term that captures a collection of disorders with overlapping motor features. Understanding the differences between Parkinson’s disease and atypical parkinsonian syndromes is essential for accurate diagnosis, appropriate treatment, and clearer expectations for progression.

As movement disorders neurologist Dr. Jonathan Isaacson explains, “Parkinsonism is a term that describes kind of the syndromic nature of these diseases that have similar features of Parkinson's disease and sister conditions that are very similar.” Historically, clinicians used the term to describe symptoms before we had modern diagnostic tools. Today, greater precision allows physicians to better distinguish Parkinson’s disease from its related but distinct counterparts.

The Hallmarks of Parkinson’s Disease

Parkinson’s disease (PD) is the most common form of parkinsonism. The four primary motor symptoms that characterize PD are:

• Bradykinesia – slowness of movement
• Tremor – involuntary rhythmic shaking when the body is still or when walking
• Rigidity – stiffness in the arms and legs
• Postural instability – balance and gait difficulties

Dr. Isaacson notes that a combination of these symptoms would be diagnostic of Parkinson's disease. While symptoms vary between individuals, PD typically develops gradually and responds well to dopaminergic therapies, which is one reason why patients today can live long, full lives with the condition.

What Makes Atypical Parkinsonism Different?

Atypical parkinsonian syndromes such as Lewy body dementia (LBD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), share features with Parkinson’s disease but also have distinguishing “red flags.” These syndromes generally progress faster, respond less robustly to PD medications, and include symptoms outside the typical motor profile.

Dr. Isaacson emphasizes that clinicians look for symptoms that “we don't see as often in Parkinson's disease” to help differentiate these disorders.

Let’s break down the major atypical syndromes and the specific features he references.

Lewy Body Dementia: Early Cognitive and Visual Symptoms

Dr. Isaacson shares that “some things we see in Lewy body more so than in Parkinson's are early cognitive features and early hallucinations.” In Parkinson’s, these typically appear later in the disease course, not near the onset.

You can learn more about Lewy body Dementia here.

Multiple System Atrophy (MSA): Autonomic and Cerebellar Features

MSA is marked by widespread involvement of the autonomic nervous system—functions we don’t consciously control, such as blood pressure and digestion. Dr. Isaacson notes that in MSA, “we see symptoms like orthostatic hypotension or other autonomic symptoms, and also cerebellar symptoms as well.”

What These Symptoms Mean:

• Orthostatic hypotension: A significant drop in blood pressure when standing up, causing dizziness or fainting. It occurs because the body fails to properly regulate blood vessel tightness and heart rate when changing position.
• Autonomic symptoms: These can include bladder dysfunction, constipation, abnormal sweating, and sexual dysfunction.
• Cerebellar signs: The cerebellum coordinates balance and fine movements. When affected, patients may experience impaired coordination, unsteady gait, slurred speech, or difficulty with rapid alternating movements.

MSA often progresses more quickly than Parkinson’s and responds poorly to standard PD medications.

Progressive Supranuclear Palsy (PSP): Eye Movement and Balance Problems

One of the hallmark signs of PSP is difficulty moving the eyes—particularly up and down.

Dr. Isaacson explains that “in supranuclear palsy, we see a lot of difficulty with vertical gaze and then also recurrent falls.”

Understanding the Key Features:

• Vertical gaze palsy: The brain areas that control voluntary up-and-down eye movements are affected. Patients struggle to look down, contributing to tripping and falls.
• Early, frequent falls: Often backwards, due to severe postural instability that arises much earlier than in Parkinson’s disease.

Corticobasal Degeneration (CBD): Markedly Asymmetric Symptoms

CBD is rare but recognizable by its strongly one-sided presentation. Dr. Isaacson describes that in this condition “one side of the body tends to have much more profound symptoms, such as significant tightening or something called dystonia.”

What These Symptoms Include:

• Asymmetrical symptoms: Unlike Parkinson’s, which may start on one side but generally becomes more bilateral, CBD often remains dramatically more severe on one side throughout its course.
• Dystonia: Involuntary, sustained muscle contractions causing twisting, abnormal postures, or painful muscle tightness.
• Alien hand phenomenon: Dr. Isaacson describes it as
  “sometimes the hand will do things that we're not cognitively aware of.” The affected hand may move, grasp, or manipulate objects seemingly on its own.

CBD is often challenging to diagnose early because of its complex mixture of motor and cognitive symptoms.

Advances in Diagnosis and Treatment

The history of Parkinson’s disease is long, dating back to its first clinical description by James Parkinson in 1817. Over time the therapeutic landscape has evolved dramatically. As Dr. Isaacson notes: “It took over 150 years before we had the first symptomatic medication for Parkinson's disease. And in the last 30 years, we've had over 30 different medications to treat the symptoms.”

This progress has transformed PD into a chronic, manageable condition for most individuals.

Equally promising are advances in diagnostic tools that help clinicians distinguish among the various parkinsonian syndromes.
“We're better able to pick up these conditions even in the prodromal period or before even the motor manifestation,” Dr. Isaacson explains. Detecting these diseases earlier brings us closer to therapies that target the underlying disease process, not just the symptoms.

He adds that the “goal would be to slow down these conditions or even halt these conditions in its track.” Research in biomarkers, skin biopsies, and precision medicine is bringing the field steadily toward this possibility.

Earlier diagnosis, more accurate categorization, and emerging disease-modifying strategies are shaping a promising future, one where earlier intervention may change the course of these conditions entirely.

For more insights on the different forms of Parkinsonism, watch our full conversation with Dr. Jonathan Isaacson in the video above.

By Alicia Barber Minteer, PhD