Is Dalfampridine (ampyra) used for gait instability, spasticity gait, or slow gait in multiple sclerosis (MS) patients?

Dalfampridine for Walking Impairment in Multiple Sclerosis

Dalfampridine (Ampyra) is specifically indicated to improve walking ability in adult patients with multiple sclerosis, demonstrated by increased walking speed, and is not indicated for gait instability or spasticity. 1

Mechanism and Indication

• Dalfampridine is a potassium channel blocker that works by restoring axonal conduction through blockade of potassium channels exposed during demyelination 2
• FDA-approved specifically as a treatment to improve walking in adult MS patients, with efficacy measured by improvements in walking speed 1
• Not indicated for treatment of spasticity, which is typically managed with different medications such as tizanidine, dantrolene, or oral baclofen 3

Efficacy for Walking Impairment

• Clinical trials demonstrated that dalfampridine improves walking speed in approximately one-third of MS patients 4
• In phase III trials, the proportion of "timed walk responders" was significantly greater with dalfampridine 10 mg twice daily than with placebo 5
• Responders showed consistent improvements in walking speed of approximately 25% during treatment 5
• Long-term studies show sustained improvement in walking speed among responders for up to 5 years, although the magnitude of improvement may decline over time 6

Effects Beyond Walking Speed

• Dalfampridine also improves:
  • Gait parameters as measured by NeuroCom composite scores 7
  • Walking distance as measured by the 2-Minute Walk Test 7
  • Balance as measured by the Berg Balance Scale 7
• These benefits are lost when the medication is discontinued but return within 2 weeks of reinitiation 7, 6

Dosing and Administration

• Maximum recommended dosage is 10 mg twice daily (approximately 12 hours apart) 1
• Higher doses show no additional benefit and significantly increase seizure risk 1
• Tablets must be taken whole; do not divide, crush, chew, or dissolve 1
• Can be taken with or without food 1

Important Safety Considerations

• Contraindicated in patients with:
  • History of seizures 1
  • Moderate to severe renal impairment (CrCl ≤50 mL/min) 1
  • History of hypersensitivity to dalfampridine 1
• Renal function should be assessed before starting treatment and monitored at least annually 1
• Even mild renal impairment (CrCl 51-80 mL/min) may increase plasma levels and seizure risk 1

Clinical Pearls

• Dalfampridine should be discontinued if no improvement in walking is observed after 4 weeks 4
• The medication works quickly, with benefits typically observed within 2 weeks of starting treatment 7
• Dalfampridine is the only FDA-approved medication specifically for improving walking in MS patients 4
• Common adverse effects include insomnia, dizziness, headache, nausea, back pain, and balance disorders 5

Distinction from Other MS Treatments

• Unlike treatments for spasticity (such as baclofen, tizanidine, or botulinum toxin), dalfampridine does not directly target muscle tone or spasms 3
• Functional electrical stimulation (FES) may be used for specific motor impairments in stroke and MS patients but addresses different aspects of gait dysfunction 3
• Modafinil may be used in MS patients for hypersomnia/fatigue but does not directly improve walking ability 3