OVERVIEW

What is Early-Onset Parkinson's Disease?

Early-onset Parkinson's disease (EOPD) refers to Parkinson's disease with an onset age under 50. Cases with onset between 21 and 50 years old are also called young-onset Parkinson's disease (YOPD), while those with onset before 21 are termed juvenile parkinsonism (JP).

This disease is rare, with some cases progressing slowly and others rapidly. Patients may experience motor symptoms such as bradykinesia, tremors, and muscle rigidity, as well as non-motor symptoms like memory decline, depression, anxiety, irritability, and impulse control disorders.

Treatment primarily focuses on medication to improve motor and non-motor symptoms, combined with psychotherapy and rehabilitation. It cannot be cured, and most cases have a poor prognosis, significantly impacting daily life.

Is Early-Onset Parkinson's Disease Common?

Early-onset Parkinson's disease is very rare and was included in China's "First List of Rare Diseases" in 2018.

It accounts for 5%–10% of all Parkinson's disease cases (the prevalence of typical Parkinson's disease in China is about 2% among those aged 65 and above). In Western countries, it constitutes around 5%, while in Japan, it accounts for approximately 10%.

The incidence of Parkinson's disease increases with age.

What Are the Differences Between Early-Onset and Typical Parkinson's Disease?

Early-onset Parkinson's disease differs from typical Parkinson's disease in several ways:

• First, typical Parkinson's disease usually occurs after age 60, while early-onset cases begin before age 50.
• Second, typical Parkinson's disease is more common, whereas early-onset cases make up only about 10% of typical cases.
• Third, typical Parkinson's disease is mostly sporadic, with rare hereditary or familial clustering, while early-onset cases often have clear genetic and familial patterns, with most patients having a positive family history.
• Fourth, the cause of typical Parkinson's disease remains unclear and is thought to involve genetic susceptibility, environmental factors, and aging. Diagnosis relies on medical history, physical signs, and imaging to rule out secondary parkinsonism or Parkinson-plus syndromes. In contrast, early-onset cases are often linked to genetic factors, with over 20 known pathogenic genes. Diagnosis includes genetic testing in addition to medical history, physical exams, and routine tests.
• Fifth, while the clinical manifestations of early-onset and typical Parkinson's disease are generally similar, early-onset cases have distinct features, such as a higher likelihood of drug-induced motor complications (e.g., dyskinesias) with levodopa treatment, more frequent mood disorders (e.g., depression, anxiety, irritability), and behavioral issues (e.g., compulsive medication use, impulse control disorders, stereotyped behaviors). They may also exhibit gene-specific systemic symptoms (e.g., gaze abnormalities, dementia, cervical dystonia) but have a lower risk of cognitive impairment (e.g., memory loss, reduced logical thinking) compared to typical cases.

SYMPTOMS

What symptoms does early-onset Parkinson's disease cause?

• Motor symptoms: The motor symptoms of early-onset Parkinson's disease are similar to those of typical Parkinson's disease, including bradykinesia, tremor, muscle rigidity, and postural/gait abnormalities.

  • Bradykinesia: Patients experience stiffness in limbs and trunk, slow and laborious movements, though muscle strength (e.g., grip, arm/leg lifting) remains largely normal. Reduced activity and slow speech are also common. Facial muscle rigidity may lead to a "mask-like" expression, while hand muscle slowness and stiffness can cause "micrographia" (handwriting becoming progressively smaller).
  • Tremor: Some patients develop uncontrollable shaking, often starting in one limb. Hand tremors may manifest as a "pill-rolling" motion of the thumb and fingers. Tremors are more noticeable at rest and worsen with stress but improve or disappear during sleep or movement. As the disease progresses, tremors may spread to other limbs, the trunk, tongue, or jaw, causing voice tremors.
  • Muscle rigidity: During physical exams, doctors may detect increased resistance when passively moving the patient's joints, described as "lead-pipe" or "cogwheel" rigidity.
  • Postural/gait abnormalities: Patients may initially show reduced arm swing or slight dragging while walking. Over time, they may develop difficulty initiating steps ("hesitation"), short shuffling steps, and a tendency to accelerate uncontrollably ("festinating gait"). Posture becomes stooped, arm swing diminishes, and turning becomes slow and difficult.

• Non-motor symptoms: Early-onset Parkinson's patients often exhibit differences in non-motor symptoms compared to typical cases, such as:

  • Mild cognitive impairment (e.g., memory loss, reduced logical thinking, poor attention), though these typically appear later.
  • Higher rates of mood disorders (e.g., depression, anxiety, irritability) and behavioral issues (e.g., compulsive medication overuse, impulse control disorders, stereotyped behaviors).
  • Less prominent constipation or olfactory dysfunction.

• Other symptoms: Certain genetic mutations linked to early-onset Parkinson's may cause distinct features, aiding diagnosis:

  • Parkin mutations: Slow progression, dystonia, bilateral symmetric symptoms, symptom improvement with sleep.
  • PINK1: Dystonia as an initial symptom.
  • ATP13A2 mutations: Rapid progression to bedridden state, with spasms, supranuclear gaze palsy, dementia, facial-laryngeal-finger tremors, hallucinations, and ocular myoclonus.
  • PLA2G6 mutations: Early non-motor/cognitive symptoms, later parkinsonism (bradykinesia, rigidity), dystonia, ataxia, dysarthria, pyramidal signs, and rapid progression with motor complications.

What severe complications can early-onset Parkinson's disease cause?

Complications vary by disease subtype, treatment response, and care quality:

• Severe motor symptoms increase fall risks, injuries, or aspiration pneumonia due to swallowing difficulties. Poor nutrition or prolonged immobility may lead to bedsores or hypostatic pneumonia. Proper care reduces these risks.
• Cognitive decline in some subtypes significantly impairs memory and thinking, reducing quality of life.
• Mood disorders (e.g., depression, anxiety, anger) are common due to the long病程. Suicide or harm to others may occur without psychological support, medication, or social/family assistance.
• Behavioral issues (e.g., compulsions, impulse control disorders) may cause medication misuse, repetitive actions, or reckless spending. Early antipsychotic treatment and supervision are crucial.

Does early-onset Parkinson's disease shorten lifespan?

Prognosis varies by subtype. Some progress slowly with minimal complications, not affecting lifespan. Others advance rapidly to dementia or immobility, potentially shortening life due to infections, injuries, or psychiatric complications.

CAUSES

Why do people develop early-onset Parkinson's disease?

Currently, most scholars believe that early-onset Parkinson's disease is related to genetic factors, possibly due to gene mutations in pathogenic genes or carrying multiple susceptibility genes. More than 20 genes clearly associated with early-onset Parkinson's disease have been identified.

Who is more likely to develop early-onset Parkinson's disease?

Individuals with a family history of early-onset Parkinson's disease are more likely to develop the condition.

Is early-onset Parkinson's disease hereditary? How is it inherited?

Some cases are hereditary, with two main inheritance patterns: autosomal dominant and autosomal recessive. Common autosomal dominant genes include SNCA, LRRK2, UCH-L1, and VPS35, while common autosomal recessive genes include Parkin, PINK1, DJ-1, ATP13A2, and PLA2G6.

Additionally, some susceptibility genes can be detected in the general population. While they do not directly cause the disease, their presence increases the risk of developing Parkinson's disease, such as GBA, MAPT, and SNCA genes. Individuals carrying multiple susceptibility genes have a significantly higher risk of developing Parkinson's disease than the general population.

DIAGNOSIS

When should early-onset Parkinson's disease be suspected?

Early-onset Parkinson's disease should be suspected when individuals aged 50 or younger exhibit bradykinesia, dystonia, limb tremors, or abnormal gait and posture. Additionally, if the patient has a family history of early-onset Parkinson's disease and presents with non-motor symptoms such as cognitive decline, mood disorders, or psychiatric disturbances, early-onset Parkinson's disease should also be considered.

What tests are needed if early-onset Parkinson's disease is suspected?

• Physical examination: Patients with suspected early-onset Parkinson's disease require a comprehensive neurological examination. Findings may include cognitive dysfunction, limb dystonia, resting tremors, or abnormal gait and posture. A minority of patients may also exhibit impaired eye movements, slurred speech, ataxia, or positive pathological signs.

• Ancillary tests:

  • Neuropsychological assessments: These include anxiety and depression scales, mental status evaluations, and cognitive function tests to identify emotional, psychiatric, or cognitive issues.
  • Genetic testing: A critical tool for definitive diagnosis.
  • Blood biochemical tests: Such as ceruloplasmin, ferritin, complete blood count, and blood smears, primarily for differential diagnosis to rule out conditions like Wilson's disease, iron storage disorders, or neuroferritinopathy, which may mimic similar symptoms.
  • Other tests: Imaging studies (e.g., brain MRI, presynaptic dopaminergic imaging), orthostatic blood pressure monitoring, autonomic function tests, Kayser-Fleischer ring examination, and lumbar puncture for cerebrospinal fluid analysis help exclude conditions like progressive supranuclear palsy, multiple system atrophy, prion diseases, or Wilson's disease.

What diseases should be differentiated from early-onset Parkinson's disease?

Early-onset Parkinson's disease has diverse clinical manifestations, requiring extensive differential diagnosis. For example:

• Patients with impaired eye movements should be differentiated from progressive supranuclear palsy (PSP), PARK9 (ATP13A2 gene), PARK15 (FBXO7 gene), PARK14 (PLA2G6 gene), or Niemann-Pick disease type C (NPC1 and NPC2 genes).
• Patients with prominent dystonia should be distinguished from dopa-responsive dystonia, PARK9, PARK14, PARK15, or iron storage disorders such as pantothenate kinase-associated neurodegeneration (PKAN) and neuroferritinopathy (NFT).

TREATMENT

Which department should be consulted for early-onset Parkinson's disease?

Neurology.

Is early-onset Parkinson's disease easy to treat? Can it be completely cured?

Different types of early-onset Parkinson's disease respond differently to medication—some show good treatment outcomes, while others are difficult to treat and progress rapidly. However, regardless of the type, there is currently no complete cure.

How is early-onset Parkinson's disease treated? What are the treatment goals?

Early-onset Parkinson's disease is primarily treated with medication, while psychological and rehabilitation therapies are also important. Enhanced care and support are necessary.

The treatment goals mainly focus on improving symptoms, enhancing quality of life, and avoiding adverse events and complications.

What are the common medications for treating early-onset Parkinson's disease?

The medications for early-onset Parkinson's disease are largely the same as those for typical Parkinson's disease and mainly include:

• Levodopa:

  • Can improve all motor symptoms in early-onset Parkinson's disease patients. Most patients respond well to levodopa, but drug-related movement complications, such as uncontrollable chorea-like or athetosis-like movements, are common and often linked to medication timing.
  • Therefore, non-levodopa medications are recommended first for early-onset Parkinson's disease patients, followed by combination therapy with low-dose levodopa to minimize movement complications.
  • Common levodopa preparations include Madopar and Sinemet, both oral medications contraindicated in patients with glaucoma, prostate hypertrophy, or schizophrenia.
  • Possible side effects include nausea, vomiting, abnormal liver function, arrhythmia, orthostatic hypotension, urinary retention, incontinence, constipation, insomnia, and hallucinations.

• Dopamine receptor agonists:

  • Can be used alone for mild cases or combined with levodopa. They are particularly effective for tremors, and some may also improve depression. They can also be first-line treatments.
  • Common drugs include bromocriptine, pergolide, piribedil, pramipexole, and ropinirole, all oral medications.
  • Possible side effects include nausea and vomiting, which can be alleviated with domperidone. Additionally, impulse control disorders may occur, leading to uncontrolled behaviors such as gambling, binge eating, compulsive shopping, or hypersexuality.

• Amantadine:

  • Can improve tremors, muscle rigidity, and bradykinesia, suitable for mild cases, either alone or in combination, but its effects are short-lived.
  • Oral dosage is typically 100 mg twice daily.
  • Possible side effects include insomnia, dizziness, headache, nausea, livedo reticularis in the lower limbs, and ankle edema.
  • Use with caution in epilepsy patients.

• MAO-B inhibitors:

  • Can be used alone or with levodopa for early or mid-to-late-stage patients, reducing levodopa dosage and delaying movement complications.
  • Common drugs include selegiline and rasagiline.
  • Possible side effects include fatigue, dry mouth, nausea, insomnia, vivid dreams, and hallucinations. May be combined with vitamin E.
  • Use with caution in psychiatric patients.

• Anticholinergics:

  • Effective for tremors and rigidity but less so for bradykinesia. Suitable for younger patients with prominent tremors.
  • Common drug: Artane (trihexyphenidyl).
  • Side effects include dry mouth, reduced saliva and sweat secretion, blurred vision, constipation, urinary retention, hallucinations, and delusions.
  • Contraindicated in glaucoma and prostate hypertrophy patients. Long-term use may impair cognitive function.

• COMT inhibitors:

  • Inhibit peripheral metabolism of levodopa, increasing its brain levels. Ineffective alone; must be combined with levodopa to enhance efficacy.
  • Common drugs: tolcapone and entacapone.
  • Possible side effects include dyskinesia, nausea, vomiting, diarrhea, liver damage, and loss of appetite.

For other non-motor symptoms, such as cognitive decline, mood disorders, or behavioral issues, symptomatic treatment is the main approach.

Might early-onset Parkinson's disease patients require surgery?

Possibly. For mid-to-late-stage patients with ineffective medication, intolerable side effects, or severe motor complications like symptom fluctuations or dyskinesia, surgical options such as deep brain stimulation (DBS) may be considered.

However, it is not effective for all patients, and medication must continue post-surgery.

DIET & LIFESTYLE

What dietary precautions should patients with early-onset Parkinson's disease take?

No special requirements; maintaining a healthy diet is sufficient.

What lifestyle precautions should patients with early-onset Parkinson's disease take?

• In the early stages when motor symptoms are mild, patients are encouraged to stay active within their limits, such as walking, tai chi, swimming, or jogging, but avoid overexertion. In moderate to advanced stages with noticeable motor symptoms, they should still try to remain active but take precautions to prevent falls or accidents. Assistive devices like walkers may be necessary, and the living environment should minimize stairs and obstructive furniture.
• Regular mental exercises and cognitive training may help delay cognitive decline.
• For patients with mood disorders or behavioral issues, caregivers should provide close supervision, psychological support, and positive reinforcement, while being vigilant for suicidal, self-harm, or aggressive tendencies.

How to care for patients with early-onset Parkinson's disease?

Depending on the patient's daily living abilities, early-stage patients can generally manage independently, while those in moderate to advanced stages require caregiver assistance:

• For bedridden patients, frequent repositioning is necessary to prevent bedsores.
• During feeding, extra caution is needed to avoid choking. A feeding tube may be required if necessary.
• Caregivers should also monitor the patient's cognitive function, emotional state, and mental behavior, addressing non-motor symptoms proactively.

Can patients with early-onset Parkinson's disease have children?

Most types of early-onset Parkinson's disease do not affect fertility but may increase the risk of passing the condition to offspring. The risk varies depending on the specific genetic mutation and inheritance pattern.

Those planning to have children should seek thorough prenatal genetic counseling. Preimplantation genetic diagnosis or screening (PGD/PGS) through assisted reproductive technology (commonly known as third-generation IVF) may be considered.

Can patients with early-onset Parkinson's disease study or work normally?

Yes, as long as motor symptoms are controlled and cognitive function, mood, and mental health permit, patients can study or work normally.

Can patients with early-onset Parkinson's disease exercise? What types of exercise are suitable?

Yes, patients are encouraged to engage in moderate exercise within their tolerance. Early-stage patients may try jogging, swimming, or tai chi, while those in moderate to advanced stages can opt for walking or tai chi. Overexertion should be avoided.

PREVENTION

Can Early-Onset Parkinson's Disease Be Prevented? How?

Yes. Individuals with a family history of early-onset Parkinson's disease should undergo prenatal diagnosis and genetic counseling before planning pregnancy to prevent the birth of affected offspring, contributing to better birth outcomes. Assisted reproductive technologies such as preimplantation genetic diagnosis or screening (PGD or PGS, commonly known as third-generation IVF) can be utilized.