MDS 2026 — Motor Complications in Parkinson's Disease

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event1178 wordssynced 2026-04-02

Congress: Movement Disorder Society (MDS) International Congress 2026 Dates: October 4-8, 2026 Location: Seoul, Korea — COEX Convention and Exhibition Center Theme: Understanding Aging in Movement Disorders

Overview

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Motor complications represent a major challenge in the long-term management of Parkinson's disease (PD), developing in the majority of patients after 5-10 years of dopaminergic therapy. These complications include motor fluctuations (wearing-off, on-off phenomena) and dyskinesias (levodopa-induced dyskinesias, LID), significantly impacting quality of life and functional independence["@jankovic2005"][@nutt2000].

...

Overview

Mermaid diagram (expand to render)

MDS 2026 will showcase advances in understanding the pathophysiology of these complications and emerging strategies for prevention and management.

Motor Fluctuations

Types of Motor Fluctuations

Wearing-Off Phenomenon

Definition: Progressive reduction in duration of benefit from each levodopa dose
Prevalence: Occurs in 50% of patients within 5 years of levodopa initiation
Clinical Features: Predictable end-of-dose akinesia, often preceded by tremor or fatigue
Mechanism: Progressive loss of nigrostriatal dopaminergic neurons → reduced buffer capacity
Management:
Reduce interdose interval
Add long-acting formulations (controlled-release levodopa)
Add dopamine agonist
Add COMT inhibitor (entacapone, opicapone)
Add MAO-B inhibitor

On-Off Phenomenon

Definition: Abrupt, unpredictable transitions between "on" (good mobility) and "off" (poor mobility)
Prevalence: Develops in 30-40% of patients after 5-10 years of treatment
Clinical Features: Unpredictable "off" episodes lasting minutes to hours
Mechanism: Downregulation of dopamine receptors, altered levodopa pharmacokinetics
Management:
Continuous dopaminergic stimulation (see below)
Subcutaneous apomorphine infusion
Deep brain stimulation

Delayed-On and No-On

Definition: Delayed or absent onset of therapeutic benefit after levodopa dose
Causes: Gastric emptying delay, competition with dietary amino acids, gastroparesis
Management: Take levodopa on empty stomach, liquid formulations, prokinetic agents

Continuous Dopaminergic Delivery

Strategies to provide more continuous dopaminergic stimulation:

| Strategy | Description | Advantages |
|----------|-------------|------------|
| Levodopa-carbidopa intestinal gel (LCIG) | Continuous intrajejunal infusion | Most continuous delivery, reduces fluctuations |
| Subcutaneous apomorphine infusion | Continuous subcutaneous pump | Reduces dyskinesias, improves "on" time |
| Subcutaneous apomorphine intermittent injections | Rescue therapy for "off" episodes | Rapid onset (10-15 minutes) |
| Extended-release formulations | Longer-acting oral medications | Convenience, reduced dosing frequency |

Levodopa-Induced Dyskinesias

Clinical Presentation

Peak-Dose Dyskinesias

Timing: Occur at peak levodopa plasma concentrations
Character: Chorea, choreoathetosis, dystonia
Localization: Most commonly involve the face, neck, and limbs
Management: Reduce levodopa dose, add amantadine

Diphasic Dyskinesias

Timing: Occur at the onset and offset of levodopa effect
Character: More severe, often ballistic movements
Management: More challenging; may require continuous delivery

Off-Period Dystonia

Timing: Occur during "off" periods, particularly early morning
Character: Painful foot/leg dystonia
Management: Extended-release levodopa, bedtime levodopa

Pathophysiology

The exact mechanisms remain under investigation but involve[@castriotoa2013]:

Pulsatile Stimulation: Intermittent levodopa dosing leads to non-physiological dopamine receptor stimulation

Receptor Plasticity: Downregulation and desensitization of post-synaptic dopamine receptors

Striatal Output Changes: Altered direct and indirect pathway activity

Cortico-Striatal Loops: Abnormal patterns in motor circuit activity

Neuroinflammation: Glial activation contributing to dyskinesia expression

Genetic Factors: Certain polymorphisms may increase susceptibility

Risk Factors

Long disease duration
Long levodopa therapy duration
Higher levodopa dose
Younger age at onset
Female gender
Lower body weight

Management Strategies

Medication Adjustment

Reduce levodopa dose: May improve dyskinesias but worsen "off" time
Increase dosing frequency: Smaller, more frequent doses
Add dopamine agonist: May allow levodopa dose reduction
Add amantadine: NMDA antagonist with anti-dyskinesia effects
Add COMT inhibitor: Improves levodopa bioavailability

Surgical Interventions

Deep Brain Stimulation (DBS): Significantly reduces dyskinesias
Subthalamic nucleus (STN) DBS: Most effective for dyskinesias
Globus pallidus interna (GPi) DBS: Preferred for patients with significant cognitive issues
Focused Ultrasound: For patients who cannot undergo DBS

Continuous Delivery Systems

Levodopa-carbidopa intestinal gel (LCIG): Reduces dyskinesias by 60-70%
Subcutaneous apomorphine infusion: Reduces dyskinesias significantly

Experimental Approaches

Adenosine A2A receptor antagonists: Istradefylline (approved in Japan)
Levodopa prodrugs: Travis-1012, ABBV-951
Gene therapy: AAV-based tyrosine hydroxylase delivery

Freezing of Gait

Clinical Features

Definition: Transient inability to generate effective stepping
Episodes: Typically last seconds, triggered by narrow spaces, turns, initiations
Prevalence: 50-70% of advanced PD patients
Impact: Major cause of falls and functional decline

Classification

| Type | Features |
|------|----------|
| Off-period freezing | Occurs during "off" states, improves with dopaminergic therapy |
| On-period freezing | Occurs during "on" states, often resistant to medication |
| Mixed | Both off and on-period freezing |

Pathophysiology

Deficits in Automaticity: Failure of internally-cued gait
Executive Dysfunction: Impaired motor planning
Visuospatial Impairment: Problems with environmental navigation
Neuroimaging: Abnormalities in frontal cortex, pedunculopontine nucleus

Management

Pharmacological

Dopaminergic medications: May improve off-period freezing
Methylphenidate: May improve gait and freezing (particularly in advanced disease)
Rivastigmine: Cholinesterase inhibitor for gait and freezing

Non-Pharmacological

cueing Strategies:
Visual cues (laser pointers, striped floors)
Auditory cues (rhythmic music, metronomes)
Tactile cues (rhythmic tapping)
Physical Therapy: Gait training, balance exercises
Assistive Devices: Walkers with laser guides
LSVT LOUD Therapy: May have secondary benefits for gait

Surgical

DBS: Particularly STN target, may improve freezing
Pedunculopontine Nucleus (PPN) DBS: Experimental for refractory freezing

Postural Instability

Clinical Features

Definition: Loss of postural reflexes leading to falls
Prevalence: Increases with disease duration
Impact: Major cause of morbidity, nursing home placement

Assessment Scales

Pull Test: Standard neurological examination
Berg Balance Scale
TUG (Timed Up and Go) Test
BESTest (Balance Evaluation Systems Test)

Management

Physical Therapy: Balance training, strengthening
Exercise Programs: Tai chi, dance (particularly tango)
Home Safety Modifications: Remove rugs, install grab bars
Assistive Devices: Canes, walkers
Medication Review: Reduce medications that cause orthostatic hypotension

Falls and Fall Prevention

Risk Factors

Previous falls
Freezing of gait
Postural instability
Cognitive impairment
Orthostatic hypotension
Visual impairment
Environmental hazards

Prevention Strategies

Comprehensive Fall Risk Assessment

Home Safety Evaluation

Regular Exercise: Focus on balance and strength

Medication Review: Minimize fall-risk medications

Vision and Hearing Assessment

Assistive Device Training

Sessions and Presentations

Expected Topics

Managing Motor Fluctuations: Beyond Oral Therapy

Levodopa-Induced Dyskinesias: New Understanding and Treatments

Freezing of Gait: From Mechanisms to Management

Deep Brain Stimulation for Motor Complications

Continuous Dopaminergic Delivery Systems

Falls and Postural Instability in PD

[MDS 2026 — Main Congress Page](/events/mds-2026)](/events)
[MDS 2026 — Parkinson's Disease Sessions](/events/mds-2026-parkinsons-sessions)](/events)
[Parkinson's Disease](/diseases/parkinsons-disease)](/proteins/parkin)
[Parkinson's Disease Treatment](/therapeutics/parkinsons-disease-treatment)](/therapeutics)
[Deep Brain Stimulation for Parkinson's](/therapeutics/deep-brain-stimulation-parkinsons)](/therapeutics)
[Levodopa-Carbidopa Intestinal Gel](/therapeutics/levodopa-carbidopa-intestinal-gel)](/therapeutics)
[Apomorphine for Parkinson's](/therapeutics/apomorphine-parkinsons)](/therapeutics)
[Freezing of Gait in Parkinson's](/diseases/freezing-gait-parkinsons)](/proteins/parkin)
[MDS 2026 — Emerging Therapeutics](/events/mds-2026-parkinsons-emerging-therapeutics)](/events)
[MDS 2026 — Clinical Trials](/events/mds-2026-parkinsons-clinical-trials)

References

[Jankovic J. Motor fluctuations and dyskinesias in Parkinson's disease (2005)](https://doi.org/10.1002/mds.20721)

[Castriotoa A, et al. Maladaptive-plasticity in Parkinson's disease (2013)](https://doi.org/10.1007/s00702-013-1043-8)

[Nutt JG, et al. Motor fluctuations in Parkinson's disease (2000)](https://doi.org/10.1001/archneur.57.3.369)

[MDS Congress 2026](https://www.mdscongress.org)

External Links

[MDS Congress 2026](https://www.mdscongress.org)
[International Parkinson and Movement Disorders Society](https://www.movementdisorders.org/)](/proteins/parkin)
[Parkinson's Foundation - Motor Symptoms](https://www.parkinson.org/)

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MDS 2026 — Motor Complications in Parkinson's Disease

Overview

Overview

Motor Fluctuations

Types of Motor Fluctuations

Wearing-Off Phenomenon

On-Off Phenomenon

Delayed-On and No-On

Continuous Dopaminergic Delivery

Levodopa-Induced Dyskinesias

Clinical Presentation

Peak-Dose Dyskinesias

Diphasic Dyskinesias

Off-Period Dystonia

Pathophysiology

Risk Factors

Management Strategies

Medication Adjustment

Surgical Interventions

Continuous Delivery Systems

Experimental Approaches

Freezing of Gait

Clinical Features

Classification

Pathophysiology

Management

Pharmacological

Non-Pharmacological

Surgical

Postural Instability

Clinical Features

Assessment Scales

Management

Falls and Fall Prevention

Risk Factors

Prevention Strategies

Sessions and Presentations

Expected Topics

Related Pages

References

External Links