What are the alternatives to Riluzole (Riluzole) for treating spinal cord injury?

Alternatives to Riluzole for Spinal Cord Injury

There are no proven pharmacological alternatives to riluzole for neuroprotection in acute spinal cord injury, as riluzole itself remains investigational and no drug therapy has yet demonstrated significant efficacy in improving functional outcomes. 1, 2

Current Evidence on Pharmacological Neuroprotection

Methylprednisolone (Controversial)

• Methylprednisolone is the only agent besides riluzole that has shown potential effectiveness in randomized controlled trials, though its results remain highly controversial. 1
• The evidence for methylprednisolone efficacy is disputed, and it is not universally recommended in current guidelines. 1

Thyrotropin-Releasing Hormone (Insufficient Evidence)

• Thyrotropin-releasing hormone demonstrated effectiveness in early trials but involved too few patients to establish definitive recommendations. 1
• This agent has not progressed to widespread clinical use due to limited evidence base. 1

Glyburide/Glibenclamide (Investigational)

• Glyburide blocks upregulated sulfonylurea receptor 1 (Sur1)-regulated nonselective cation channels that cause persistent post-injury sodium currents. 1
• The SCING trial (phase I/II) is delivering glyburide within 8 hours to patients with ASIA grade A/B/C C2-8 injuries, with results expected in 2020. 1
• This remains investigational and is not yet available as a clinical alternative. 1

Hepatocyte Growth Factor (Investigational)

• Intrathecal HGF has shown promise in non-human primate studies for enhancing ventral motor neuron survival and improving motor outcomes. 1
• A phase I/II placebo-controlled study (KP-100IT) is recruiting patients with modified Frankel scale A/B1/B2 cervical injuries within 72 hours of injury. 1
• This agent is not yet clinically available outside of research protocols. 1

Supportive Management Strategies (Non-Pharmacological Neuroprotection)

Early Surgical Decompression

• Recent AOSpine guidelines emphasize timing of surgical decompression as a key clinical question, though specific surgical trials have not proven effectiveness for neuroprotection. 1
• Early decompression remains a cornerstone of management despite lack of definitive trial evidence. 1

Hemodynamic and Respiratory Management

• Maintain adequate spinal cord perfusion through blood pressure management to prevent secondary ischemic injury from hypotension. 3
• Implement respiratory weaning protocols combining abdominal contention belts, active physiotherapy, and mechanically-assisted insufflation/exsufflation devices. 1
• Use aerosol therapy combining beta-2 mimetics and anticholinergics for respiratory support. 1

Early Rehabilitation Bundle

• Begin early mobilization and stretching techniques for at least 20 minutes per zone to maintain joint amplitudes and prevent spasticity. 1
• Implement early intermittent bladder catheterization as soon as the patient is medically stable to minimize urological complications. 1

Management of Neuropathic Pain (Secondary Complication)

First-Line Oral Agents

• Initiate gabapentinoids (pregabalin or gabapentin) as first-line treatment, with gabapentin titrated to 2400 mg daily in divided doses. 4, 1
• Alternatively, start tricyclic antidepressants such as amitriptyline at 10-25 mg/day as first-line therapy. 4, 1
• For inadequate monotherapy response, combine gabapentinoid with amitriptyline or add serotonin reuptake inhibitors. 1, 4

Topical Treatments

• Apply topical compounded creams containing amitriptyline for localized neuropathic pain with minimal systemic effects. 4
• Consider combination topical baclofen, amitriptyline, and ketamine gel for motor function improvement after 4 weeks. 4

Multimodal Analgesia During Surgery

• Introduce multimodal analgesia combining non-opioid analgesics, antihyperalgesic drugs (ketamine), and opioids during surgical management to prevent prolonged pain. 1

Critical Limitations

The fundamental reality is that no drug therapy—including riluzole—has yet shown significant efficacy in improving functional outcomes in spinal cord injury patients. 2, 1 The field has conducted numerous trials over decades with few proven gains for patients, and riluzole itself remains under investigation in the ongoing RISCIS phase II/III trial. 5, 6, 7

Common Pitfalls to Avoid

• Do not delay surgical decompression or supportive care while waiting for pharmacological neuroprotection, as these remain unproven. 1
• Avoid using succinylcholine beyond 48 hours post-injury due to risk of hyperkalemia from nerve deafferentation. 1
• Do not administer folic acid before ruling out vitamin B12 deficiency, as this may precipitate subacute combined degeneration. 8
• Monitor for severe bradycardia and cardiac arrest risk (16% incidence) in cervical injuries during the first 2-4 weeks, particularly during tracheal suctioning. 3