Salil Singh

Dysphagia in stroke patients.

Swallowing musculature is asymmetrically represented in both motor cortices. Stroke affecting the hemisphere with the dominant swallowing projection results in dysphagia and clinical recovery has been correlated with compensatory changes in the previously non-dominant, unaffected hemisphere. This asymmetric bilaterality may explain why up to half of stroke patients are dysphagic and why many will regain a safe swallow over a comparatively short period. Despite this propensity for recovery, dysphagia carries a sevenfold increased risk of aspiration pneumonia and is an independent predictor of mortality. The identification, clinical course, pathophysiology, and treatment of dysphagia after stroke are discussed in this review.

Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions.

BACKGROUND & AIMS Oropharyngeal dysphagia is an important disability that occurs after stroke; it contributes to aspiration pneumonia and death, and current modalities for rehabilitation of dysphagia have uncertain efficacy. We therefore examined the role of pharyngeal electrical stimulation (PES) in expediting human swallowing recovery after experimental (virtual) and actual (stroke) brain lesions. METHODS First, healthy subjects (n = 13) were given 1-Hz repetitive transcranial magnetic stimulation to induce a unilateral virtual lesion in pharyngeal motor cortex followed by active or sham (control) PES. Motor-evoked potentials and swallow accuracy were recorded before and after the lesion to assess PES response. Thereafter, 50 acute dysphagic stroke patients underwent either a dose-response study, to determine optimal parameters for PES (n = 22), or were assigned randomly to groups given either active or sham (control) PES (n = 28). The primary end point was the reduction of airway aspiration at 2 weeks postintervention. RESULTS In contrast to sham PES, active PES reversed the cortical suppression induced by the virtual lesion (F(7,70) = 2.7; P = .015) and was associated with improvement in swallowing behavior (F(3,42) = 5; P = .02). After stroke, 1 PES treatment each day (U = 8.0; P = .043) for 3 days (U = 10.0) produced improved airway protection compared with controls (P = .038). Active PES also reduced aspiration (U = 54.0; P = .049), improved feeding status (U = 58.0; P = .040), and resulted in a shorter time to hospital discharge (Mantel-Cox log-rank test, P = 0.038). CONCLUSIONS This pilot study of PES confirms that it is a safe neurostimulation intervention that reverses swallowing disability after virtual lesion or stroke.

Unilateral suppression of pharyngeal motor cortex to repetitive transcranial magnetic stimulation reveals functional asymmetry in the hemispheric projections to human swallowing

Inhibitory patterns of repetitive transcranial magnetic stimulation (rTMS) were applied to pharyngeal motor cortex in order to establish its role in modulating swallowing activity and provide evidence for functionally relevant hemispheric asymmetry. Healthy volunteers underwent single pulse TMS before and for 60 min after differing intensities of 1 Hz rTMS (n= 9, 6 male, 3 female, mean age 34 ± 3 years) or theta burst stimulation (TBS) (n= 9, 6 male, 3 female, mean age 37 ± 4 years). Electromyographic responses recorded from pharynx and hand were used as a measure of cortico‐motor pathway excitability. Swallowing behaviour was then examined with a reaction time protocol, before and for up to 60 min after the most effective inhibitory protocol (1 Hz) applied to each hemisphere. Interventions were conducted on separate days and compared to sham using ANOVA. Only high intensity 1 Hz rTMS consistently suppressed pharyngeal motor cortex immediately and for up to 45 min (−34 ± 7%, P≤ 0.001). Adjacent hand and contralateral pharyngeal motor cortex showed no change in response (−15 ± 12%, P= 0.14 and 15 ± 12%, P= 0.45, respectively). When used to unilaterally disrupt each hemisphere, rTMS to pharyngeal motor cortex with the stronger responses altered normal (−12 ± 3%, P≤ 0.001) and fast (−9 ± 4%, P≤ 0.009) swallow times, not seen following rTMS to the contralateral cortex or after sham. Thus, suppression of pharyngeal motor cortex to rTMS is intensity and frequency dependent, which when applied to each hemisphere reveals functionally relevant asymmetry in the motor control of human swallowing.

Deglutitive laryngeal closure in stroke patients

Background: Dysphagia has been reported in up to 70% of patients with stroke, predisposing them to aspiration and pneumonia. Despite this, the mechanism for aspiration remains unclear. Aims: To determine the relationship between bolus flow and laryngeal closure during swallowing in patients with stroke and to examine the sensorimotor mechanisms leading to aspiration. Methods: Measures of swallowing and bolus flow were taken from digital videofluoroscopic images in 90 patients with stroke and 50 healthy adults, after repeated volitional swallows of controlled volumes of thin liquid. Aspiration was assessed using a validated Penetration–Aspiration Scale. Oral sensation was also measured by electrical stimulation at the faucial pillars. Results: After stroke, laryngeal ascent was delayed (mean (standard deviation (SD)) 0.31 (0.06) s, p<0.001), resulting in prolongation of pharyngeal transit time (1.17 (0.07) s, p<0.001) without a concomitant increase in laryngeal closure duration (0.84 (0.04) s, p = 0.9). The delay in laryngeal elevation correlated with both the severity of aspiration (r = 0.5, p<0.001) and oral sensation (r = 0.5, p<0.001). Conclusions: After stroke, duration of laryngeal delay and degree of sensory deficit are associated with the severity of aspiration. These findings indicate a role for sensorimotor interactions in control of swallowing and have implications for the assessment and management of dysphagia after stroke.

Evaluating Oral Stimulation as a Treatment for Dysphagia after Stroke

Deglutitive aspiration is common after stroke and can have devastating consequences. While the application of oral sensory stimulation as a treatment for dysphagia remains controversial, data from our laboratory have suggested that it may increase corticobulbar excitability, which in previous work was correlated with swallowing recovery after stroke. Our study assessed the effects of oral stimulation at the faucial pillar on measures of swallowing and aspiration in patients with dysphagic stroke. Swallowing was assessed before and 60 min after 0.2-Hz electrical or sham stimulation in 16 stroke patients (12 male, mean age = 73 ± 12 years). Swallowing measures included laryngeal closure (initiation and duration) and pharyngeal transit time, taken from digitally acquired videofluoroscopy. Aspiration severity was assessed using a validated penetration-aspiration scale. Preintervention, the initiation of laryngeal closure, was delayed in both groups, occurring 0.66 ± 0.17 s after the bolus arrived at the hypopharynx. The larynx was closed for 0.79 ± 0.07 s and pharyngeal transit time was 0.94 ± 0.06 s. Baseline swallowing measures and aspiration severity were similar between groups (stimulation: 24.9 ± 3.01; sham: 24.9 ± 3.3, p = 0.2). Compared with baseline, no change was observed in the speed of laryngeal elevation, pharyngeal transit time, or aspiration severity within subjects or between groups for either active or sham stimulation. Our study found no evidence for functional change in swallow physiology after faucial pillar stimulation in dysphagic stroke. Therefore, with the parameters used in this study, oral stimulation does not offer an effective treatment for poststroke patients.

Targeting Unlesioned Pharyngeal Motor Cortex Improves Swallowing in Healthy Individuals and After Dysphagic Stroke

BACKGROUND & AIMS Patients with stroke experience swallowing problems (dysphagia); increased risk of aspiration pneumonia, malnutrition, and dehydration; and have increased mortality. We investigated the behavioral and neurophysiological effects of a new neurostimulation technique (paired associative stimulation [PAS]), applied to the pharyngeal motor cortex, on swallowing function in healthy individuals and patients with dysphagia from stroke. METHODS We examined the optimal parameters of PAS to promote plasticity by combining peripheral pharyngeal (electrical) with cortical stimulation. A virtual lesion was used as an experimental model of stroke, created with 1-Hz repetitive transcranial magnetic stimulation over the pharyngeal cortex in 12 healthy individuals. We tested whether hemispheric targeting of PAS altered swallowing performance before applying the technique to 6 patients with severe, chronic dysphagia from stroke (mean of 38.8 ± 24.4 weeks poststroke). RESULTS Ten minutes of PAS to the unlesioned pharyngeal cortex reversed (bilaterally) the cortical suppression induced by virtual lesion (lesioned: F(1,9) = 21.347, P = .001; contralesional: F(1,9) = 9.648, P = .013; repeated-measures analysis of variance) compared with sham PAS. It promoted changes in behavior responses measured with a swallowing reaction time task (F(1,7) = 21.02, P = .003; repeated-measures analysis of variance). In patients with chronic dysphagia, real PAS induced short-term bilateral changes in the brain; the unaffected pharyngeal cortex had increased excitability (P = .001; 95% confidence interval, 0.21-0.05; post hoc paired t test) with reduced penetration-aspiration scores and changes in swallowing biomechanics determined by videofluoroscopy. CONCLUSIONS The beneficial neurophysiological and behavioral properties of PAS, when applied to unlesioned brain, provide the foundation for further investigation into the use of neurostimulation as a rehabilitative approach for patients with dysphagia from stroke.

Characterizing the application of transcranial direct current stimulation in human pharyngeal motor cortex

Transcranial direct current stimulation (tDCS) is a novel intervention that can modulate brain excitability in health and disease; however, little is known about its effects on bilaterally innervated systems such as pharyngeal motor cortex. Here, we assess the effects of differing doses of tDCS on the physiology of healthy human pharyngeal motor cortex as a prelude to designing a therapeutic intervention in dysphagic patients. Healthy subjects (n = 17) underwent seven regimens of tDCS (anodal 10 min 1 mA, cathodal 10 min 1 mA, anodal 10 min 1.5 mA, cathodal 10 min 1.5 mA, anodal 20 min 1 mA, cathodal 20 min 1 mA, Sham) on separate days, in a double blind randomized order. Bihemispheric motor evoked potential (MEP) responses to single-pulse transcranial magnetic stimulation (TMS) as well as intracortical facilitation (ICF) and inhibition (ICI) were recorded using a swallowed pharyngeal catheter before and up to 60 min following the tDCS. Compared with sham, both 10 min 1.5 mA and 20 min 1 mA anodal stimulation induced increases in cortical excitability in the stimulated hemisphere (+44 +/- 17% and +59 +/- 16%, respectively; P < 0.005) whereas only 10 min 1.5 mA cathodal stimulation induced inhibition (-26 +/- 4%, P = 0.02). There were neither contralateral hemisphere changes nor any evidence for ICI or ICF in driving the ipsilateral effects. In conclusion, anodal tDCS can alter pharyngeal motor cortex excitability in an intensity-dependent manner, with little evidence for transcallosal spread. Anodal stimulation may therefore provide a useful means of stimulating pharyngeal cortex and promoting recovery in dysphagic patients.

The upper oesophageal sphincter.

Abstract  The upper oesophageal sphincter (UOS) is a high‐pressure zone comprising functional activity of three adjacent muscles together with cartilage and connective tissue. Its primary function is to allow food into the oesophagus and prevent air ingestion. However, it must also allow the reflux of material during belching or vomiting. Cricopharyngeus is the most important muscle with contributions from inferior pharyngeal constrictor and cervical oesophagus. Basal tone within the UOS is contributed to by all three muscles with asymmetry in the axial plane. Relaxation of the UOS occurs during swallowing as well as in sleep while UOS pressure rises with stress, slow oesophageal distension, intra‐oesophageal acid infusion and pharyngeal stimulation with air or water. Many physiological characteristics have been attributed to UOS function following videofluoroscopic swallow examinations, manometry and electromyography but a range of normal values remains controversial and their utility uncertain. The result has been that pathological change is inconsistently characterized and management is instigated without a satisfactory evidence base. In this article, we review the anatomy, physiology and pathophysiology of the UOS along with the current opinions on investigation and treatment of UOS dysfunction.

A Magnetic Resonance Spectroscopy Study of Brain Glutamate in a Model of Plasticity in Human Pharyngeal Motor Cortex

BACKGROUND & AIMS Coordinated delivery of peripheral and cortical stimuli (paired associative stimulation [PAS]) has been shown to induce plasticity in limb motor cortex, however, its application in pharyngeal motor cortex and the molecular mechanisms involved in human neuroplasticity remain uncertain. Because neuroplasticity appears to form the basis for functional recovery of digestive functions such as swallowing after brain injury, the aim of this study was to characterize the induction of cortical plasticity in human pharyngeal motor cortex through PAS applied to pharyngeal musculature and investigate the potential role of glutamate in this process. METHODS Fifteen healthy volunteers completed a series of experiments in which cortical excitability was assessed through pharyngeal motor evoked potential amplitudes in response to transcranial magnetic stimulation. The optimal parameters and interhemispheric interactions of PAS in the bilaterally represented pharyngeal system initially were investigated. Cortical glutamate after PAS then was assessed with magnetic resonance spectroscopy. RESULTS The greatest increase in cortical pharyngeal excitability was seen if paired stimuli were separated by 100 ms (F[15,210] = 2.28; P < or = .05). Cortical excitability increased over 2 hours with analogous albeit lesser changes in the contralateral hemisphere. A focal and transient reduction in glutamate was found in the stimulated pharyngeal motor cortex (F[1,12] = 21.9; P = .001), without changes in any other measured brain metabolites. CONCLUSIONS This study shows that PAS-induced plasticity in the human pharyngeal motor system is both timing- and hemisphere-dependent and provides novel evidence for the potential role of glutamate in modulating this effect.

Rapid rate magnetic stimulation of human sacral nerve roots alters excitability within the cortico-anal pathway

Abstract  Sacral nerve root stimulation (SNS) can produce dramatic symptomatic improvement in faecal incontinence (FI). However, the physiological mechanism behind this improvement remains unknown. One hypothesis is that SNS may modulate cortico‐anal pathways and drive compensatory changes within the spinal cord or cerebral cortex that beneficially alter sphincter function. Our aim was to assess whether short‐term experimental SNS can induce changes in the human cortico‐anal pathway. Eight healthy volunteers (mean age 30 years) were studied. Subjects were investigated on three separate occasions and randomized to either active (5 and 15 Hz) or sham rapid‐rate lumbosacral magnetic stimulation (rLSMS). Anal sphincter electromyograms (EMG) were recorded from an anal probe following single‐pulse transcranial magnetic stimulation, at baseline, immediately, 30 and 60 min following rLSMS at either (i) 5 Hz for 15 min, (ii) 15 Hz for 15 min or (iii) sham stimulation for 15 min. In addition, manometry and anal sphincter sensation was measured in a subset of subjects. Interventions were compared to sham using anova. Fifteen hertz rLSMS increased cortico‐anal EMG response amplitude in the 1 h postintervention (F4, 28 = 3.2, P = 0.027), without a shift in response latency. This effect was not demonstrated with either 5 Hz or sham stimulation. rLSMS had no short‐term effect on sensation or physiology. Short‐term magnetic stimulation of the sacral nerve roots induces changes in cortico‐anal excitability which is frequency specific. These data support the hypothesis that SNS produces some of its beneficial effect in patients with FI by altering the excitability of the cortico‐anal pathway.