Unlocking Relief: Dextromethorphan-Quinidine as a Palliative Intervention for Jaw Clonus in ALS

Key Message : Amyotrophic lateral sclerosis patients suffer from pain due to spasms and contractions. Jaw spasms are painful and can lead to loss of dentition and poor nutrition. With our case we would like to highlight a potential treatment option of dextromethorphan-quinidine to treat jaw spasms.

Abstract:

Introduction:
Jaw spasms/clonus is a rare but painful condition experienced by amyotrophic lateral sclerosis (ALS) patients.1 We present a case of jaw spasms successfully treated with dextromethorphan-quinidine.

Objective:
To highlight dextromethorphan-quinidine as a potential treatment option for jaw Spasms/clonus in ALS patients.

Case Report:
A 70 year-old female, diagnosed with ALS four years prior, was on oral riluzole 50 mg twice daily and edaravone 105 mg daily. Initial symptoms were limb weakness, progressing to bulbar issues like dysarthria, drooling and mild dysphagia. She denied pseudobulbar symptoms. Two years post-diagnosis, progressive weakness necessitated motorized wheelchair and night-time non-invasive ventilation (NIV).
The patient reported new “violent” jaw contractions and spasms, triggered by eating, causing pain, chipped teeth (requiring extraction) and tongue biting. Dextromethorphan-Quinidine (20/10mg) orally twice daily was started after electrocardiogram ruled out prolonged QT interval. On follow-up, the patient expressed significant improvement in jaw spasms/contractions, pain and eating ability, plus reduced dysphagia symptoms. No side effects were noted.

Discussion:
Jaw spasm/clonus is a rare painful complication in ALS. The involuntary, rhythmic contractions are often triggered by jaw activation.1 Skeletal muscle relaxants like baclofen and tizanidine, and sedatives such as benzodiazepines can treat spasticity from upper motor neuron dysfunction however, dosage required to treat is generally high and are limited by sedation, increased weakness, tolerance and dependence. Dextromethorphan-Quinidine is approved for pseudobulbar affect (PBA) in ALS. Emerging data supports its off-label use for bulbar symptoms like sialorrhea and speech/swallowing dysfunction.2 Proposed mechanisms include effects on sigma-1 receptors (S1R) and glutamate excitotoxicity, impacting on cranial nerve motor neurons in the medulla oblongata.3 No severe side effects are reported but avoid in prolonged QT interval. In our patient, dextromethorphan-quinidine effectively alleviated jaw spasms, and improved dysphagia symptoms.

Conclusion:
Dextromethorphan-Quinidine is a potential treatment option for jaw spasms/clonus in ALS.

References: 1. Kumar, R., Blackband, J., & Wagle Shukla, A. (2024). Rhythmic Jaw Movements in Amyotrophic Lateral Sclerosis: Is It Clonus or Tremor? Tremor and Other Hyperkinetic Movements, 14(1), 8. https://doi.org/10.5334/tohm.845
2. Smith, R., Pioro, E., Myers, K., Sirdofsky, M., Goslin, K., Meekins, G., Yu, H., Wymer, J., Cudkowicz, M., Macklin, E. A., Schoenfeld, D., & Pattee, G. (2017). Enhanced Bulbar Function in Amyotrophic Lateral Sclerosis: The Nuedexta Treatment Trial. Neurotherapeutics, 14(3), 762–772. https://doi.org/10.1007/s13311-016-0508-5
3. Taylor, C. P., Traynelis, S. F., Siffert, J., Pope, L. E., & Matsumoto, R. R. (2016). Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use. Pharmacology & Therapeutics (Oxford), 164, 170–182. https://doi.org/10.1016/j.pharmthera.2016.04.010