MDS 2026 — Motor Complications in Parkinson's Disease

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

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].

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

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].

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]:

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

Sessions and Presentations

Expected Topics

Related Pages

• [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

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/)