Document Type : Original Article

Authors

1 Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Department of Neurology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

3 Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Swallowing is one of the most complex functions of the central nervous system (CNS), which is controlled by different parts of the brain. Oropharyngeal dysphagia (OD) is one of the most common complications after stroke. Despite a variety of behavioral, compensatory, and rehabilitative methods, many stroke patients still suffer from swallowing disorders that adversely affect their quality of life (QOL). The aim of this study was to evaluate the effect of pyridostigmine on patients with post-stroke dysphagia.
Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out on 40 patients suffering from post-stroke dysphagia. Patients were assigned randomly into two groups: intervention and control groups (20 in each group). The intervention group was treated with pyridostigmine (60 mg, three times a day, 30 minutes before each meal for three weeks), and the control group received placebo treatment in the same way. All patients (intervention and control) were evaluated according to National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Functional Communication Measures (FCM)/American Speech-Language-Hearing Association (ASHA) criteria at baseline and after three weeks of intervention. Values of P < 0.05 were considered statistically significant.
Results: In the intervention group, the mean values of NIHSS, mRS, and ASHA/FCM were significantly reduced following three weeks of treatment with pyridostigmine (P = 0.002, P = 0.003, and P < 0.001, respectively), but no significant differences were found in the mean NIHSS, mRS, and ASHA/FCM in the placebo group.
Conclusion: Although pyridogestamine is somewhat effective in post-stroke dysphagia, it has not been shown to be more important in preventing aspiration pneumonia and length of hospital stay.

Keywords

  1. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 2095-128.
  2. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Heart disease and stroke statistics-2014 update. Circulation 2014; 129(3): e28-e292.
  3. Ludlow CL. Central nervous system control of voice and swallowing. J Clin Neurophysiol 2015; 32(4): 294-303.
  4. Rofes L, Muriana D, Palomeras E, Vilardell N, Palomera E, Alvarez-Berdugo D, et al. Prevalence, risk factors and complications of oropharyngeal dysphagia in stroke patients: A cohort study. Neurogastroenterol Motil 2018; e13338. [Epub ahead of print].
  5. Gonzalez-Fernandez M, Ottenstein L, Atanelov L, Christian AB. Dysphagia after stroke: An overview. Curr Phys Med Rehabil Rep 2013; 1(3): 187-96.
  6. Smithard DG, O'Neill PA, Parks C, Morris J. Complications and outcome after acute stroke. Does dysphagia matter? Stroke 1996; 27(7): 1200-4.
  7. Mann G, Hankey GJ, Cameron D. Swallowing disorders following acute stroke: prevalence and diagnostic accuracy. Cerebrovasc Dis 2000; 10(5): 380-6.
  8. Ickenstein GW, Stein J, Ambrosi D, Goldstein R, Horn M, Bogdahn U. Predictors of survival after severe dysphagic stroke. J Neurol 2005; 252(12): 1510-6.
  9. Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R. Dysphagia after stroke: Incidence, diagnosis, and pulmonary complications. Stroke 2005; 36(12): 2756-63.
  10. Ashford J, McCabe D, Wheeler-Hegland K, Frymark T, Mullen R, Musson N, et al. Evidence-based systematic review: Oropharyngeal dysphagia behavioral treatments. Part III--impact of dysphagia treatments on populations with neurological disorders. J Rehabil Res Dev 2009; 46(2): 195-204.
  11. Jawad LA. Poisonous Fishes. In: Jawad LA, editor. Dangerous fishes of the Eastern and Southern Arabian Peninsula. Cham, Switzerland: Springer International Publishing; 2018. p. 155-229.
  12. Power ML, Fraser CH, Hobson A, Singh S, Tyrrell P, Nicholson DA, et al. Evaluating oral stimulation as a treatment for dysphagia after stroke. Dysphagia 2006; 21(1): 49-55.
  13. Rofes L, Vilardell N, Clave P. Post-stroke dysphagia: Progress at last. Neurogastroenterol Motil 2013; 25(4): 278-82.
  14. Carnaby GD, LaGorio L, Silliman S, Crary M. Exercise-based swallowing intervention (McNeill Dysphagia Therapy) with adjunctive NMES to treat dysphagia post-stroke: A double-blind placebo-controlled trial. J Oral Rehabil 2020; 47(4): 501-10.
  15. Hong DG, Yoo DH. A comparison of the swallowing function and quality of life by oral intake level in stroke patients with dysphagia. J Phys Ther Sci 2017; 29(9): 1552-4.
  16. Cohan SL, Pohlmann JL, Mikszewski J, O'Doherty DS. The pharmacokinetics of pyridostigmine. Neurology 1976; 26(6 PT 1): 536-9.
  17. Andersen JB, Engeland A, Owe JF, Gilhus NE. Myasthenia gravis requiring pyridostigmine treatment in a national population cohort. Eur J Neurol 2010; 17(12): 1445-50.
  18. Maggi L, Mantegazza R. Treatment of myasthenia gravis: Focus on pyridostigmine. Clin Drug Investig 2011; 31(10): 691-701.
  19. Glikson M, Achiron A, Ram Z, Ayalon A, Karni A, Sarova-Pinchas I, et al. The influence of pyridostigmine administration on human neuromuscular functions--studies in healthy human subjects. Fundam Appl Toxicol 1991; 16(2): 288-98.
  20. Blonski W, Vela MF, Freeman J, Sharma N, Castell DO. The effect of oral buspirone, pyridostigmine, and bethanechol on esophageal function evaluated with combined multichannel esophageal impedance-manometry in healthy volunteers. J Clin Gastroenterol 2009; 43(3): 253-60.
  21. Adams HP, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, et al. Baseline NIH Stroke Scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 1999; 53(1): 126-31.
  22. Kasner SE, Chalela JA, Luciano JM, Cucchiara BL, Raps EC, McGarvey ML, et al. Reliability and validity of estimating the NIH stroke scale score from medical records. Stroke 1999; 30(8): 1534-7.
  23. Schlegel D, Kolb SJ, Luciano JM, Tovar JM, Cucchiara BL, Liebeskind DS, et al. Utility of the NIH Stroke Scale as a predictor of hospital disposition. Stroke 2003; 34(1): 134-7.
  24. Hage V. The NIH stroke scale: A window into neurological status. Nurs Spect 2011; 24(15): 44-9.
  25. Newcommon NJ, Green TL, Haley E, Cooke T, Hill MD. Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin Scale. Stroke 2003; 34(2): 377-8.
  26. Portas J, Correa D, Queija D, Arantes LMRB, Viana LS, Carvalho AL. Effect of induction chemotherapy on swallowing in head and neck cancer patients. Asian Pac J Cancer Prev 2019; 20(1): 91-6.
  27. Sitoh YY, Lee A, Phua SY, Lieu PK, Chan SP. Bedside assessment of swallowing: A useful screening tool for dysphagia in an acute geriatric ward. Singapore Med J 2000; 41(8): 376-81.
  28. Roy N, Stemple J, Merrill RM, Thomas L. Dysphagia in the elderly: Preliminary evidence of prevalence, risk factors, and socioemotional effects. Ann Otol Rhinol Laryngol 2007; 116(11): 858-65.
  29. Goulding R, Bakheit AM. Evaluation of the benefits of monitoring fluid thickness in the dietary management of dysphagic stroke patients. Clin Rehabil 2000; 14(2): 119-24.
  30. Whelan K. Inadequate fluid intakes in dysphagic acute stroke. Clin Nutr 2001; 20(5): 423-8.
  31. DePippo KL, Holas MA, Reding MJ, Mandel FS, Lesser ML. Dysphagia therapy following stroke: A controlled trial. Neurology 1994; 44(9): 1655-60.
  32. Carnaby G, Hankey GJ, Pizzi J. Behavioural intervention for dysphagia in acute stroke: A randomised controlled trial. Lancet Neurol 2006; 5(1): 31-7.
  33. Munakata M, Kobayashi K, Niisato-Nezu J, Tanaka S, Kakisaka Y, Ebihara T, et al. Olfactory stimulation using black pepper oil facilitates oral feeding in pediatric patients receiving long-term enteral nutrition. Tohoku J Exp Med 2008; 214(4): 327-32.
  34. Perez I, Smithard DG, Davies H, Kalra L. Pharmacological treatment of dysphagia in stroke. Dysphagia 1998; 13(1): 12-6.
  35. Guptill JT, Soni M, Meriggioli MN. Current treatment, emerging translational therapies, and new therapeutic targets for autoimmune myasthenia gravis. Neurotherapeutics 2016; 13(1): 118-31.
  36. Huang J, Liu X, Luo X, Tang C, Xu M, Wood L, et al. Effects of fluoxetine on poststroke dysphagia: A clinical retrospective study. J Stroke Cerebrovasc Dis 2018; 27(11): 3320-7.
  37. Humphries TJ, Castell DO. Effect of oral bethanechol on parameters of esophageal peristalsis. Dig Dis Sci 1981; 26(2): 129-32.
  38. Hollis JB, Castell DO. Effects of cholinergic stimulation on human esophageal peristalsis. J Appl Physiol 1976; 40(1): 40-3.
  39. Lee KL, Lim OK, Lee JK, Park KD. Treatment of dysphagia with pyridostigmine bromide in a patient with the pharyngeal-cervical-brachial variant of guillain-barre syndrome. Ann Rehabil Med 2012; 36(1): 148-53.
  40. Aydogdu I, Ertekin C, Tarlaci S, Turman B, Kiylioglu N, Secil Y. Dysphagia in lateral medullary infarction (Wallenberg's syndrome): An acute disconnection syndrome in premotor neurons related to swallowing activity? Stroke 2001; 32(9): 2081-7.