The BDNF polymorphism Val66Met may be predictive of swallowing improvement post pharyngeal electrical stimulation in dysphagic stroke patients

Essa, Hoda H.; Vasant, Dipesh H.; Raginis-Zborowska, Alicja; Payton, Antony; Michou, Emilia; Hamdy, Shaheen

doi:10.1111/nmo.13062

Cited by 14 publications

(20 citation statements)

References 35 publications

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“…In their study, those with the Met allele had shown increased altered response with improvement as assessed by the dysphagia rating scale. They suggested that the negative effects of the Met allele may be switched to protective roles in certain circumstances such as after neurostimulation 44 . This is in sharp contrast to our results that advocate the protective role of the Val allele.…”

Section: Discussioncontrasting

confidence: 99%

“…They suggested that the negative effects of the Met allele may be switched to protective roles in certain circumstances such as after neurostimulation. 44 This is in sharp contrast to our results that advocate the protective role of the Val allele. These discrepancies may be attributable to the different swallowing outcome parameters employed in the two studies.…”

Section: Ta B L E 1 Baseline Demographics Of Patientscontrasting

confidence: 99%

“…The association of BDNF rs6265 with swallowing was first demonstrated in an animal study where microinjections into the nucleus tractus solitarii inhibited swallowing function 43 . Its role in swallowing plasticity was reported by Essa et al, 44 who explored the relationship of this polymorphism in relation to pharyngeal electrical and proposed that BDNF polymorphism plays a significant role in the pharynx. In their study, those with the Met allele had shown increased altered response with improvement as assessed by the dysphagia rating scale.…”

Section: Discussionmentioning

confidence: 95%

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Role of rs6265 BDNF polymorphisms and post‐stroke dysphagia recovery—A prospective cohort study

Kim

Park

et al. 2020

Neurogastroenterology Motil

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Background: Previous studies suggest that specific genes may predispose some to increased risk of dysphagia in the geriatric population, but whether these genes may affect swallowing recovery after a stroke is unknown. This study investigated whether single-nucleotide polymorphisms (SNP) of the brain-derived neurotrophic factor (BDNF), catechol-O-methyl transferase, apolipoprotein E, interleukin-1 receptor antagonist, and dopamine, which have been linked to swallowing, could adversely affect the prognosis of post-stroke dysphagia. Methods: In this study, 218 subjects with confirmed post-stroke dysphagia were enrolled. The primary endpoint was failed recovery from nil per mouth (NPM) status with the first 3 months post-stroke. Key Results: The Val/Val group from the rs6265, BDNF, showed higher score changes on the Functional Oral Intake Scale at 1 month. The proportion of patients with recovery from NPM status within the first 1 month was 60.8% in the Val/Val group, which was statistically higher than those in the Met allele groups (38.1%, P = .017). At 3 months, the BDNF rs6265 showed significant group differences in Modified Barium Swallow Impairment Profile © score changes with the Val/Val allele leading to greater improvement. However, no single SNP was associated with increased risk of poor recovery with persistence of NPM at 3 months post-stroke. Conclusions and Inferences: Those with the dominant Val/Val phenotype of BDNF manifested with faster and greater improvement than the Met-phenotypes. Based on our results, the BDNF Val allele may play a positive role with faster score improvement and rapid recovery from NPM than the Met allele.

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Section: Discussioncontrasting

confidence: 99%

Section: Ta B L E 1 Baseline Demographics Of Patientscontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 95%

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Role of rs6265 BDNF polymorphisms and post‐stroke dysphagia recovery—A prospective cohort study

Kim

Park

et al. 2020

Neurogastroenterology Motil

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“…In six studies [26, 30, 33, 55, 89, 103] comprising 1241 cases (585 patients with a GG genotype and 656 without) (Fig. 3) showed patients with AIS who carried at codon 196 of the BDNF , the GA or AA genotypes were more likely to have poor outcome: OR 1.41 (1.02–1.94, p = 0.04).…”

Section: Resultsmentioning

confidence: 99%

Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases

et al. 2019

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Background The influences of genetic variants on functional clinical outcomes following stroke are unclear. In order to reliably quantify these influences, we undertook a comprehensive meta-analysis of outcomes after acute intracerebral haemorrhage (ICH) or ischaemic stroke (AIS) in relation to different genetic variants. Methods PubMed, PsycInfo, Embase and Medline electronic databases were searched up to January 2019. Outcomes, defined as favourable or poor, were assessed by validated scales (Barthel index, modified Rankin scale, Glasgow outcome scale and National Institutes of Health stroke scale). Results Ninety-two publications comprising 31,895 cases met our inclusion criteria. Poor outcome was observed in patients with ICH who possessed the APOE4 allele: OR =2.60 (95% CI = 1.25-5.41, p = 0.01) and in AIS patients with the GA or AA variant at the BDNF-196 locus: OR = 2.60 (95% CI = 1.25-5.41, p = 0.01) or a loss of function allele of CYP2C19: OR = 2.36 (95% CI = 1.56-3.55, p < 0.0001). Poor outcome was not associated with APOE4: OR = 1.02 (95% CI = 0.81-1.27, p = 0.90) or IL6-174 G/C: OR = 2.21 (95% CI = 0.55-8.86, p = 0.26) in patients with AIS. Conclusions We demonstrate that recovery of AIS was unfavourably associated with variants of BDNF and CYP2C19 genes whilst recovery of ICH was unfavourably associated with APOE4 gene.

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“…Previous studies (7)(8)(9)(10)(11)(12)(13) have reported that genetic polymorphisms may affect the outcomes of stroke. For example, the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been linked to poor motor recovery after stroke (7).…”

Section: Introductionmentioning

confidence: 99%

Potential Prognostic Impact of Dopamine Receptor D1 (rs4532) Polymorphism in Post-stroke Outcome in the Elderly

Park

Kim

et al. 2021

Front. Neurol.

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Background: Single-nucleotide polymorphisms (SNPs) may affect post-stroke motor recovery, and some SNPs have been implicated in swallowing disturbances after stroke. Certain SNPs may also have altered influences according to different age.Objective: This post-hoc study investigated whether SNPs have different effects on dysphagia recovery between the elderly vs. young stroke patients.Methods: Analysis was conducted from a previous study including 218 stroke subjects with dysphagia. They were stratified into two groups, aged <65 and aged ≥65 years. The primary outcome was persistence of nil per mouth (NPM) at 3 months post-stroke onset. Association between outcome and nine different SNPs were investigated.Results: The elderly group (50%, n = 103) showed poorer swallowing outcomes than the young group. The minor allele of the dopamine receptor D1 (DRD1, rs4532) polymorphism showed potential association (p = 0.022) with an increased risk of NPM at 12 weeks post-stroke in the elderly, both in the additive (OR, 2.94; 95% CI, 1.17–7.37) and dominant models (OR, 2.93; 95% CI, 1.04–8.23) but did not reach statistical significance after Bonferonni correction. Logistic regression analysis showed that in those aged ≥65 years, models including the minor allele of rs4532 predicted the risk of the poor outcome with good accuracies even after adjustment of clinical factors, such as previous pneumonia episodes (AUROC, 0.86; 95% CI, 0.79–0.93) or the National Institutes of Health Stroke Scale (AUROC, 0.82; 95% CI, 0.67–0.92). In contrast, those aged <65 years seemed not to be affected by the presence of the rs4532 polymorphism, and models that included intubation history (AUROC, 0.81; 95% CI, 0.73–0.90) or previous pneumonia episodes (AUROC, 0.77; 95% CI, 0.68–0.87) showed modest levels of accuracies in predicting NPM at 12 weeks poststroke.Conclusions: Our study suggests a possible association between the rs4532 and post-stroke swallowing recovery, primarily in those aged ≥65 years. Certain SNPs may lead to less favorable outcomes in the elderly. The gene–age interaction should be considered in post-stroke swallowing recovery.Clinical Trial Registration:https://www.clinicaltrials.gov, Unique identifier [NCT03577444].

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The BDNF polymorphism Val66Met may be predictive of swallowing improvement post pharyngeal electrical stimulation in dysphagic stroke patients

Abstract: Our findings suggest an association between BDNF and stimulation induced swallowing recovery. Further work will be required to validate these observations and demonstrate clinical utility in patients.

Cited by 14 publications

References 35 publications

Role of rs6265 BDNF polymorphisms and post‐stroke dysphagia recovery—A prospective cohort study

Role of rs6265 BDNF polymorphisms and post‐stroke dysphagia recovery—A prospective cohort study

Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases

Potential Prognostic Impact of Dopamine Receptor D1 (rs4532) Polymorphism in Post-stroke Outcome in the Elderly

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