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Dysphagia in a patient with lateral medullary syndrome: Insight into the central control of swallowing
GASTROENTEROLOGY 2001;121:420 – 426
CASE REPORTS Dysphagia in a Patient With Lateral Medullary Syndrome: Insight Into the Central Control of Swallowing ROSEMARY MARTINO,*,‡ NORAH TERRAULT,§ FRANCES EZERZER,* DAVID MIKULIS,‡,|| and NICHOLAS E. DIAMANT*,‡,§,¶ *Department of Speech Language Pathology, ‡Toronto Western Research Institute, and Departments of §Gastroenterology, ||Medical Imaging, and ¶Physiology, Toronto Western Hospital, University Health Network and the University of Toronto, Toronto, Ontario, Canada
Background & Aims: Central control of swallowing is regulated by a central pattern generator (CPG) positioned dorsally in the solitary tract nucleus and neighboring medullary reticular formation. The CPG serially activates the cranial nerve motor neurons, including the nucleus ambiguus and vagal dorsal motor nucleus, which then innervate the muscles of deglutition. This case provides insight into the central control of swallowing. Methods: A 65-year-old man with a right superior lateral medullary syndrome presented with a constellation of symptoms, including dysphagia. The swallow was characterized using videofluoroscopy and esophageal motility and the results were compared with magnetic resonance imaging (MRI) findings. Results: Videofluoroscopy showed intact lingual propulsion and volitional movements of the larynx. Distal pharyngeal peristalsis was absent, and the bolus did not pass the upper esophageal sphincter. Manometry showed proximal pharyngeal contraction and normal peristaltic activity in the lower esophagus (smooth muscle), but motor activity of the upper esophageal sphincter and proximal esophagus (striated muscle) was absent. MRI showed a lesion of the dorsal medulla. Conclusions: These findings are compatible with a specific lesion of the connections from a programming CPG in the solitary tract nucleus to nucleus ambiguus neurons, which supply the distal pharynx, upper esophageal sphincter, and proximal esophagus. There is functional preservation of the CPG control center in the solitary tract nucleus and of the vagal dorsal motor nucleus neurons innervating the smooth muscle esophagus.
ateral medullary syndrome or Wallenburg’s syndrome is caused by a vascular event in the territory of the posterior inferior cerebellar artery or the vertebral artery.1 The resulting infarction of the rostral portion of the lateral medulla in the brain stem produces a very specific constellation of neurological symptoms that may include dysphagia2,3 (Table 1). A detailed assessment of dysphagia in a patient with lateral medullary syndrome
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provided insights into the central control of swallowing through combining results from videofluoroscopic assessment of swallow physiology, manometry, and magnetic resonance imaging (MRI) in the same patient. A portion of this case study has been published in abstract form.4
Case Report A 65-year-old white man diagnosed with right superior lateral medullary syndrome first presented for assessment of dysphagia 12 weeks after the initial neurological event. During this 12-week period, the patient underwent a stormy course with aspiration pneumonia requiring a tracheostomy and insertion of a percutaneous gastrostomy tube. On examination, the typical neurological findings of lateral medullary syndrome were evident. The patient had a right facial paresis, a crossed sensory deficit involving right face and left arm, deviation of his palate to the left, a right Horner’s syndrome, and right-sided ataxia and incoordination. Hoarseness was present. Severe dysphagia to both solids and liquids was associated with episodes of choking, coughing, and gagging. The patient localized his dysphagia to the suprasternal region and was entirely dependent on tube feedings. To characterize the dysphagia further, videofluoroscopy was used to assess the oropharyngeal phases of swallowing. At a later visit, esophageal motility studies were also used to assess the function of the pharyngoesophageal region and the striated and smooth muscle segments of the esophageal body, including the lower esophageal sphincter (LES). Videofluoroscopy was performed using the modified barium swallow technique described by Logemann.5 This procedure was administered at the initial assessment and at 9, 14, and 27 months after the stroke. At the initial assessment, the motor Abbreviations used in this paper: CPG, central pattern generator; LES, lower esophageal sphincter; MRI, magnetic resonance imaging; NA, nucleus ambiguus; NTS, nucleus of the solitary tract; UES, upper esophageal sphincter. © 2001 by the American Gastroenterological Association 0016-5085/01/$35.00 doi:10.1053/gast.2001.26291
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Table 1. Features Common With Lateral Medullary Syndrome Signs Ipsilateral Pain, numbness, and impaired sensation over half of face Ataxia of limbs, falling to side of lesion Horner’s syndrome (i.e., constricted pupil, ptosis, decreased sweating on half of face) Dysphagia, hoarseness, dysarthria, paralysis of ipsilateral palate and vocal folds, diminished ipsilateral gag reflex Contralateral Impaired pain and thermal sense over half of limbs and trunk
Structures affected Nucleus and tract of CN V Inferior cerebellar peduncle, spinocerebellar tract Descending sympathetic tract
Efferent fibers of CN’s IX and X, NA
Spinothalamic tract
CN, cranial nerve.
function of the tongue was intact at the oral preparatory phase, including coordinated bolus formation and mastication. The patient was observed to propel both liquid and puree boluses to the point of the oropharynx, after which there was no bolus propulsion of any kind, and the pharyngeal swallow was considered absent. He was recommended to remain on tube feeding and prescribed swallowing trials of ice chips using specific swallow maneuvers. At the 9-month assessment, there continued to be adequate oral propulsion caused by a functional lingual driving force. There was, however, slight reduction of posterior lingual elevation resulting in trace oropharyngeal spillage. Anterior and vertical elevation of the larynx was now evident and only slightly reduced. Epiglottic deflection continued to be absent, likely because of the reduced vertical movements of the larynx and posterior tongue. Posterior tongue base movements to the posterior pharyngeal wall were intact. The major abnormality was with pharyngeal and upper esophageal sphincter (UES) function. No contraction of the middle and inferior pharyngeal constrictors was evident, thereby rendering bolus drive absent at this level. The UES failed to open adequately, and as a consequence, the liquid and puree boluses pooled in the hypopharynx with small amounts penetrating into the upper airway. The patient did not sense the penetration but with prompting was able to reliably occlude the airway and expectorate the penetrated material back into the hypopharynx. Also with prompting, the patient was able to extend the elevation of the larynx in both range and time. This maneuver permitted small amounts of especially liquid bolus to move beyond the UES and into the esophagus. He was recommended to remain on tube feedings but to advance his swallowing trials to include liquid and pureed foods while practicing volitional elevation of the larynx. At the 14-month assessment, the swallow had improved enough to permit an oral diet of liquids to soft solids. Ade-
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quate elevation of the posterior tongue and larynx permitted propulsion of both liquid and soft solid boluses to the level of the pyriform sinuses. To advance the bolus through the UES, albeit in piecemeal fashion, the patient consistently and without effort implemented volitional elevation of the larynx. At the 27-month assessment, the patient continued to safely manage an oral diet using volitional laryngeal elevation. Pharyngeal bolus transport was more efficient, and airway protection improved with more consistent epiglottic deflection. Over the course of 2 years, the pharyngeal swallowing phase showed improvements but continued to be impaired. The dysphagia was, however, successfully compensated with implementation of laryngeal elevation strategies. MRI was used to provide optimal visualization of the brain stem structures. The initial MRI performed at 4 weeks showed a mass in the dorsolateral aspect of the ponto-medullary junction of the brain stem with extension of edema into the right middle cerebellar peduncle. MRI studies at 4 and 7 months after onset showed a decrease in the overall size of the lesion, indicating resolution of edema and leaving behind a residual infarct cavity measuring approximately 5 mm in diameter (Figure 1). The lesion was centered in the dorsal medulla just anterior to the floor of the fourth ventricle and rostral to the obex. Esophageal motility studies were performed at 8 months after the neurological event (1 month after the last MRI and 1 month before a videofluoroscopic assessment) using 2 different manometric catheters and with a conventional water-perfused system. The first catheter contained 6 lumens with 5 recording apertures 5 cm apart and with the sixth aperture 3 cm proximal to the distal opening. With this manometric catheter, a “station pull through” technique was used to assess function of the UES and LES. The catheter was then positioned within the esophageal body such that the first aperture was 2 cm below the UES and the lowermost aperture was 2 cm above the LES. The second manometric catheter contained a “sleeve” assembly and was used to better characterize UES function. The “sleeve” was 2.5 cm in length. Recording apertures were also present at 0.5 and 2.5 cm above and 0.5 cm below the sleeve, and when the sleeve was correctly positioned across the UES, additional recordings could be obtained from the pharynx, esophageal body, and the LES. Using the first catheter assembly (Figure 2), the measured UES pressure varied from 20 to 130 mm Hg with respiratory fluctuation evident within the zone. With an attempted swallow, a distinct pharyngeal contraction wave was discerned proximally but was absent in the 1 cm above the UES. There was no effective relaxation of the UES. Furthermore, no definite contractile activity was present in the proximal 6 cm of the upper esophagus, the region corresponding primarily to striated esophageal muscle. Peristaltic contractions were evident in the more distal 15 cm of the esophageal body, the region corresponding primarily to smooth muscle esophagus. The mean LES pressure was normal and measured 36 mm Hg.
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Figure 1. MRI 7 months after presentation. (A ) T1- and (B) T2-weighted axial images and a (C ) T1-weighted sagittal image show an infarct cavity confined to a small region of the dorsolateral medulla just anterior to the floor of the fourth ventricle and rostral to the obex.
The LES relaxation-contraction sequence in response to the swallow was normal in appearance. Using the “sleeve” catheter assembly (Figure 3), similar motility information was obtained with more detail in the pharyngoesophageal region. In response to a swallow, a discrete pharyngeal contraction was evident 2.5 cm above the UES, but there was no swallow activity at the level of the UES or in the pharynx just above or the upper esophagus just below the UES. The mean basal UES pressure was 44 mm Hg. Esophageal contractile activity measured at a distance 8 cm below the sleeve sensor was normal. LES function was again shown to be intact.
Discussion In this patient, the matured lateral medullary syndrome was associated with a very specific form of dysphagia. The reflex pharyngeal and esophageal components of the swallow were initiated, and the oral and proximal portions of the pharyngeal swallow were intact. Adequate elevation of the posterior tongue and larynx were also stimulated with minimal conscious effort by the patient. However, although the UES had significant resting tone, the UES failed to relax and contract, and the striated muscles of the distal pharynx and proximal
esophagus failed to contract as part of the swallow response. On the other hand, the remainder of the swallow in the esophageal body, including the smooth muscle portion and LES, appeared to be intact and functioned normally. This pattern of motor abnormalities could be explained anatomically by a selective lesion involving primarily the neural elements connecting the circuitry of the central pattern generator (CPG), which controls swallowing and resides more dorsally and medially in the brain stem, to the region of the nucleus ambiguus (NA) supplying efferent motor fibers to the unresponsive areas. The NA is situated deeper and more laterally in the brain stem (Figure 4). Although the initial clinical picture and MRI findings indicated more extensive brain stem involvement, the later MRI findings on recovery would fit with this hypothesis. Furthermore, the combined findings lend support to the present concepts of how major brain stem elements interact to produce the sequential activation of the swallowing musculature. These concepts have arisen in large part from animal studies in sheep and rats in which the esophagus is virtually all striated muscle and the cat, which has a portion of the
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ing control mechanism, the “swallowing center,” is bilaterally represented by connected halves located in the medulla. Jean6,12 and Kessler13 have provided evidence for 2 levels of integration within the swallowing center.6,12,13 One level of integration (dorsal) is involved in the initiation of swallowing and the organization of the entire swallowing sequence, whereas a second level of organization (ventral) appears to serve primarily as a connecting pathway to the various motor pools involved in the swallowing sequence. Afferent information from the periphery enters into the NTS (dorsal), the afferent reception portal of the swallowing center to synapse on “premotor neurons.” This sensory information can initiate deglutition and the swallowing sequence, alter previously initiated activity in the swallowing center, and therefore modify ongoing motor activity. The esophageal premotor neurons also receive input from pharyngeal premotor neurons in the intermediate and interstitial
Figure 2. Esophageal motility recording with 6-lumen perfused catheter system. The proximal recording site is 2 cm below the UES, and the distal site is 2 cm above the LES. Note absence of contraction just below the UES and presence of a peristaltic contraction through the distal two thirds of the esophagus. Sw, swallow.
distal esophagus composed of smooth muscle as in the human. A proposed overview of some main brain stem structures, their connections, the direction of sequential activation, and the potential site of the lesion in the patient are diagrammed in Figure 5. Present concepts picture the CPG for swallowing and activation of the muscles of deglutition as a serial network of linked neurons within the nucleus of the solitary tract (NTS) and neighboring reticular formation, such that once activated, its rostrocaudal organization produces sequential excitation of motor neurons serving muscles along the deglutition pathway.6 – 8 At least 2 subnetworks are considered to be present, one for the oropharyngeal phase and the other in the subnucleus centralis for the esophageal phase of swallowing.9,10 Even segmental subcircuits have been suggested for the striated muscle portion.11 Presumably a similar subnucleus subserves the smooth muscle esophagus via the dorsal motor nucleus of the vagus. Anatomically, the swallow-
Figure 3. Esophageal motility study with a 6-lumen perfused catheter system having a sleeve positioned in the UES. The proximal recording site is 3 cm above the sleeve. Note absence of relaxation and contraction in the UES and absence of contraction in the striated muscle of the pharynx just above the UES and the esophageal body just below the UES. Normal motor function is present in the esophageal body and LES below. Sw, swallow.
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Figure 4. Cross-section of human brain stem and proposed site of lesion. Functionally, the lesion is positioned to spare the dorsomedial structures that would contain the CPG for swallowing in the NTS and the neighboring reticular formation, the dorsal motor nucleus of the vagus (DMNV), which serves the smooth muscle esophagus and LES, and perhaps the NA, which serves the striated muscle of the pharynx, UES, and upper esophagus. However, the lesion is positioned to interrupt the connections between the CPG circuitry and the NA serving these latter regions. XII, hypoglossal nucleus; Vn, trigeminal nucleus; Vt, trigeminal tract.
subnuclei of the NTS and connect with third-order esophageal neurons in multiple nuclei of the reticular formation, including the parvocellular nucleus.10 The reticular formation nuclei contain interneurons that are active as part of the CPG control for swallowing and esophageal peristalsis.14,15 In our patient, the swallow could be initiated and progress through the entire sequence, excluding only the striated muscle of the UES and adjacent distal pharynx and proximal esophagus. Therefore, the NTS subnuclei that receive afferent information and connect with each other, along with the neighboring reticular formation elements that are also involved with programming the swallow sequence, appear to be spared by the lesion. However, motor output to the unresponsive areas was absent. Swallow-induced motor activity of the striated muscle of the pharynx, UES, and esophagus occurs via vagal efferents originating in the NA. In rats, there is a topographic subdivision within the NA such that efferents originating more rostrally innervate the pharyngeal musculature, those fibers from neurons more medial and caudal innervate the striated muscle of the esophagus, and presumably fibers to the UES arise from in between.16 The persistent movements of the posterior tongue, proximal pharynx, and larynx in our patient
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indicate a sparing of the more rostral NA and its connections to the swallowing control mechanism. The presence of resting tone in the UES suggests that the NA motor neurons supplying this region are in fact also functional on the affected or unaffected side. These neurons are normally tonically active and are inhibited first and then activate forcefully as part of the programmed swallow sequence.17,18 They and the motor neurons to the pharynx and striated muscle esophagus can be activated by a direct paucisynaptic pathway from the cortex and via stimulation of the vagus or other cranial nerves.13,19,20 Furthermore, the UES tone decreases during sleep in the relative absence of swallowing.21 Therefore, other inputs to these neurons can apparently operate independent of the swallowing CPG. Absence of the normal swallow-induced relaxation and contraction of the UES, along with absence of contraction in the adjacent pharyngeal and esophageal striated muscle, is con-
Figure 5. Overview of brain stem control mechanism for swallowing and proposed site of lesion. Functionally, the lesion is positioned to interrupt the connections between the CPG circuitry for swallowing in the NTS and the neighboring reticular formation and the NA region, which serves the striated muscle of the pharynx, UES, and upper esophagus. The CPG and its series of subnuclei within the NTS, the NA, and the dorsal motor nucleus of the vagus (DMNV), which serves the smooth muscle esophagus and LES, are largely unaffected.
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sistent with damage primarily to the second (ventral) level of organization that acts as a connecting pathway to the NA neurons serving these regions during the swallowing sequence. Motor neurons to the smooth muscle esophagus, including the LES, are located in two subregions of the dorsal motor nucleus of the vagus. This nucleus lies in the central gray matter of the medulla and is lateral to the hypoglossal nerve and dorsal to the NA.22 Evidence from studies of the cat LES suggests that the rostral region contains neurons that mediate excitation and the caudal region neurons that mediate inhibition of the esophagus.23 The documentation of coordinated activity of the smooth muscle esophagus and LES in the patient indicates that the motor nucleus for this region (dorsal motor nucleus of the vagus), its connections to the brain stem circuitry that controls the entire ordered sequence of the swallow (NTS and neighboring reticular formation), and this circuitry itself are in large part intact and functional. In this patient, a lesion apparently localized to one side of the brain stem has caused significant neuromuscular dysfunction and dysphagia, although the mechanism for control of swallowing is bilaterally represented in the medulla. Similar observations have been made in other patients with brain stem vascular accidents.2,24,25 These investigators explain the finding by visualizing the requirement for integrated bilateral control that will be disrupted by a lesion on only one side. However, in the face of destruction of the region of the CPG on one side, stimulation to the opposite intact side can result in the entire swallow sequence.7 Therefore, maintenance of the swallow sequence in this patient suggests that, as elsewhere in the brain, there is functional asymmetry and unilateral damage to the dominant side will produce functional abnormality, while unilateral involvement of the nondominant side will have little or no effect on function. This type of asymmetry is well described for regions of the cortex involved with the induction of swallowing, with the subsequent recovery from a unilateral stroke with dysphagia being associated with enhancement of function on the nondominant cortical hemisphere.26,27 Some of the dysphagia that occurs intermittently with cervical spine surgery has also been attributed to functional asymmetry.28
Summary The assessment of dysphagia in a patient with lateral medullary syndrome has provided insight into and support for the present concepts of the central brain stem control of swallowing. The findings indicate that this
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control in humans is similar to that proposed and arising from animal studies.
References 1. Sacco RL, Freddo L, Bello JA, Odel JG, Onesti ST, Mohr JP. Wallenberg’s lateral medullary syndrome. Clinical-magnetic resonance imaging correlations. Arch Neurol 1993;50:609 – 614. 2. Vigderman AM, Chavin JM, Kososky C, Tahmoush AJ. Aphagia due to pharyngeal constrictor paresis from acute lateral medullary infarction. J Neurol Sci 1998;155:208 –210. 3. Kim JS, Lee JH, Suh DC, Lee MC. Spectrum of lateral medullary syndrome. Correlation between clinical findings and magnetic resonance imaging in 33 subjects. Stroke 1994;25:1405–1410. 4. Terrault N, Erzerzer F, Diamant NE. Central control of swallowing in a patient with lateral medullary syndrome. Clin Invest Med 1993;16(Suppl):B44. 5. Logemann JA. Manual for the videofluorographic study of swallowing. 2nd ed. Austin, TX: Pro-Ed, 1993. 6. Jean A. Localization and activity of medullary swallowing neurones. J Physiol 1972;64:227–268. 7. Jean A. Brain stem control of swallowing: neural network and cellular mechanisms. Physiol Rev 2001;81:929 –969. 8. Doty RW. Neural organization of deglutition. In: Code CF, ed. Handbook of Physiology. Section 6: Alimentary canal. Washington, DC: American Physiological Society, 1968:1861–1902. 9. Bieger D. Neuropharmacologic correlates of deglutition: lessons from fictive swallowing. Dysphagia 1991;6:147–164. 10. Broussard DL, Lynn RB, Wiedner EB, Altschuler SM. Solitarial premotor neuron projections to the rat esophagus and pharynx: implications for control of swallowing. Gastroenterology 1998; 114:1268 –1275. 11. Lu WY, Bieger D. Vagovagal reflex motility patterns of the rat esophagus. Am J Physiol 1998;274:R1425–R1435. 12. Jean A. Nucleus tractus solitarii and deglutiton: monamines, excitatory amino acids and cellular properties. In: Baracco R, ed. Nucleus of the solitary tract. Boca Raton, FL: CRC, 1994:361– 375. 13. Kessler JP, Jean A. Identification of the medullary swallowing regions in the rat. Exp Brain Res 1985;57:256 –263. 14. Bieger D. The brainstem esophagomotor network pattern generator: a rodent model. Dysphagia 1993;8:203–208. 15. Jean A. Brainstem organization of the swallowing network. Brain Behav Evol 1984;25:109 –116. 16. Bieger D, Hopkins DA. Viscerotopic representation of the upper alimentary tract in the medulla oblongata in the rat: the nucleus ambiguus. J Comp Neurol 1987;262:546 –562. 17. Asoh R, Goyal RK. Manometry and electromyography of the upper esophageal sphincter in the opossum. Gastroenterology 1978; 74:514 –520. 18. Doty RW, Bosma JF. An electromyographic analysis of reflex deglutition. J Neurophysiol 1956;19:44 – 60. 19. Jean A, Car A. Inputs to the swallowing medullary neurons from the peripheral afferent fibers and the swallowing cortical area. Brain Res 1979;178:567–572. 20. Zoungrana OR, Amri MA, Car A, Roman C. Intracellular activity of motoneurons of the rostral nucleus ambiguus during swallowing in sheep. J Neurophysiol 1997;77:909 –922. 21. Kahrilas PJ, Dodds WJ, Dent J, Haeberle B, Hogan WJ, Arndorfer RC. Effect of sleep, spontaneous gastroesophageal reflux, and a meal on upper esophageal sphincter pressure in normal human volunteers. Gastroenterology 1987;92:466 – 471. 22. Collman PI, Tremblay L, Diamant NE. The central vagal efferent supply to the esophagus and lower esophageal sphincter of the cat. Gastroenterology 1993;104:1430 –1438. 23. Rossiter CD, Norman WP, Jain M, Hornby PJ, Benjamin S, Gillis
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26.
27.
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RA. Control of lower esophageal sphincter pressure by two sites in dorsal motor nucleus of the vagus. Am J Physiol 1990;259: G899 –G906. Neumann S, Buchholz D, Jones B, Palmer J. Pharyngeal dysfunction after lateral medullary infarction is bilateral: review of 15 additional cases [abstr]. Dysphagia 1995;10:136. Neumann S, Buchholz D, Wuttge-Hannig A, Hannig C, Prosiegel M, Schroter-Morasch H. Bilateral pharyngeal dysfunction after lateral meduallary infarction [abstr]. Dysphagia 1994;9:263. Hamdy S, Aziz Q, Rothwell JC, Singh KD, Barlow J, Hughes DG, Tallis RC, Thompson DG. The cortical topography of human swallowing musculature in health and disease. Nature 1996;2:1217– 1224. Hamdy S, Aziz Q, Rothwell JC, Power M, Singh KD, Nicholson DA, Tallis RC, Thompson DG. Recovery of swallowing after dysphagic
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stroke relates to functional reorganization in the intact motor complex. Gastroenterology 1998;115:1104 –1112. 28. Martin R, Neary MA, Diamant NE. Dysphagia following anterior cervical spine surgery. Dysphagia 1995;12:2– 8.
Received January 31, 2001. Accepted March 28, 2001. Address requests for reprints to: Rosemary Martino, M.A., M.Sc., Toronto Western Hospital, University Health Network, Department of Speech Language Pathology, Fell Pavilion, 4th floor, Room no. 171, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. e-mail: [email protected]; fax: (416) 603-6204. Supported by a grant from the Medical Research Council of Canada. The authors thank Phillip Collman for the figures.
CASE REPORTS Dysphagia in a Patient With Lateral Medullary Syndrome: Insight Into the Central Control of Swallowing ROSEMARY MARTINO,*,‡ NORAH TERRAULT,§ FRANCES EZERZER,* DAVID MIKULIS,‡,|| and NICHOLAS E. DIAMANT*,‡,§,¶ *Department of Speech Language Pathology, ‡Toronto Western Research Institute, and Departments of §Gastroenterology, ||Medical Imaging, and ¶Physiology, Toronto Western Hospital, University Health Network and the University of Toronto, Toronto, Ontario, Canada
Background & Aims: Central control of swallowing is regulated by a central pattern generator (CPG) positioned dorsally in the solitary tract nucleus and neighboring medullary reticular formation. The CPG serially activates the cranial nerve motor neurons, including the nucleus ambiguus and vagal dorsal motor nucleus, which then innervate the muscles of deglutition. This case provides insight into the central control of swallowing. Methods: A 65-year-old man with a right superior lateral medullary syndrome presented with a constellation of symptoms, including dysphagia. The swallow was characterized using videofluoroscopy and esophageal motility and the results were compared with magnetic resonance imaging (MRI) findings. Results: Videofluoroscopy showed intact lingual propulsion and volitional movements of the larynx. Distal pharyngeal peristalsis was absent, and the bolus did not pass the upper esophageal sphincter. Manometry showed proximal pharyngeal contraction and normal peristaltic activity in the lower esophagus (smooth muscle), but motor activity of the upper esophageal sphincter and proximal esophagus (striated muscle) was absent. MRI showed a lesion of the dorsal medulla. Conclusions: These findings are compatible with a specific lesion of the connections from a programming CPG in the solitary tract nucleus to nucleus ambiguus neurons, which supply the distal pharynx, upper esophageal sphincter, and proximal esophagus. There is functional preservation of the CPG control center in the solitary tract nucleus and of the vagal dorsal motor nucleus neurons innervating the smooth muscle esophagus.
ateral medullary syndrome or Wallenburg’s syndrome is caused by a vascular event in the territory of the posterior inferior cerebellar artery or the vertebral artery.1 The resulting infarction of the rostral portion of the lateral medulla in the brain stem produces a very specific constellation of neurological symptoms that may include dysphagia2,3 (Table 1). A detailed assessment of dysphagia in a patient with lateral medullary syndrome
L
provided insights into the central control of swallowing through combining results from videofluoroscopic assessment of swallow physiology, manometry, and magnetic resonance imaging (MRI) in the same patient. A portion of this case study has been published in abstract form.4
Case Report A 65-year-old white man diagnosed with right superior lateral medullary syndrome first presented for assessment of dysphagia 12 weeks after the initial neurological event. During this 12-week period, the patient underwent a stormy course with aspiration pneumonia requiring a tracheostomy and insertion of a percutaneous gastrostomy tube. On examination, the typical neurological findings of lateral medullary syndrome were evident. The patient had a right facial paresis, a crossed sensory deficit involving right face and left arm, deviation of his palate to the left, a right Horner’s syndrome, and right-sided ataxia and incoordination. Hoarseness was present. Severe dysphagia to both solids and liquids was associated with episodes of choking, coughing, and gagging. The patient localized his dysphagia to the suprasternal region and was entirely dependent on tube feedings. To characterize the dysphagia further, videofluoroscopy was used to assess the oropharyngeal phases of swallowing. At a later visit, esophageal motility studies were also used to assess the function of the pharyngoesophageal region and the striated and smooth muscle segments of the esophageal body, including the lower esophageal sphincter (LES). Videofluoroscopy was performed using the modified barium swallow technique described by Logemann.5 This procedure was administered at the initial assessment and at 9, 14, and 27 months after the stroke. At the initial assessment, the motor Abbreviations used in this paper: CPG, central pattern generator; LES, lower esophageal sphincter; MRI, magnetic resonance imaging; NA, nucleus ambiguus; NTS, nucleus of the solitary tract; UES, upper esophageal sphincter. © 2001 by the American Gastroenterological Association 0016-5085/01/$35.00 doi:10.1053/gast.2001.26291
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Table 1. Features Common With Lateral Medullary Syndrome Signs Ipsilateral Pain, numbness, and impaired sensation over half of face Ataxia of limbs, falling to side of lesion Horner’s syndrome (i.e., constricted pupil, ptosis, decreased sweating on half of face) Dysphagia, hoarseness, dysarthria, paralysis of ipsilateral palate and vocal folds, diminished ipsilateral gag reflex Contralateral Impaired pain and thermal sense over half of limbs and trunk
Structures affected Nucleus and tract of CN V Inferior cerebellar peduncle, spinocerebellar tract Descending sympathetic tract
Efferent fibers of CN’s IX and X, NA
Spinothalamic tract
CN, cranial nerve.
function of the tongue was intact at the oral preparatory phase, including coordinated bolus formation and mastication. The patient was observed to propel both liquid and puree boluses to the point of the oropharynx, after which there was no bolus propulsion of any kind, and the pharyngeal swallow was considered absent. He was recommended to remain on tube feeding and prescribed swallowing trials of ice chips using specific swallow maneuvers. At the 9-month assessment, there continued to be adequate oral propulsion caused by a functional lingual driving force. There was, however, slight reduction of posterior lingual elevation resulting in trace oropharyngeal spillage. Anterior and vertical elevation of the larynx was now evident and only slightly reduced. Epiglottic deflection continued to be absent, likely because of the reduced vertical movements of the larynx and posterior tongue. Posterior tongue base movements to the posterior pharyngeal wall were intact. The major abnormality was with pharyngeal and upper esophageal sphincter (UES) function. No contraction of the middle and inferior pharyngeal constrictors was evident, thereby rendering bolus drive absent at this level. The UES failed to open adequately, and as a consequence, the liquid and puree boluses pooled in the hypopharynx with small amounts penetrating into the upper airway. The patient did not sense the penetration but with prompting was able to reliably occlude the airway and expectorate the penetrated material back into the hypopharynx. Also with prompting, the patient was able to extend the elevation of the larynx in both range and time. This maneuver permitted small amounts of especially liquid bolus to move beyond the UES and into the esophagus. He was recommended to remain on tube feedings but to advance his swallowing trials to include liquid and pureed foods while practicing volitional elevation of the larynx. At the 14-month assessment, the swallow had improved enough to permit an oral diet of liquids to soft solids. Ade-
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quate elevation of the posterior tongue and larynx permitted propulsion of both liquid and soft solid boluses to the level of the pyriform sinuses. To advance the bolus through the UES, albeit in piecemeal fashion, the patient consistently and without effort implemented volitional elevation of the larynx. At the 27-month assessment, the patient continued to safely manage an oral diet using volitional laryngeal elevation. Pharyngeal bolus transport was more efficient, and airway protection improved with more consistent epiglottic deflection. Over the course of 2 years, the pharyngeal swallowing phase showed improvements but continued to be impaired. The dysphagia was, however, successfully compensated with implementation of laryngeal elevation strategies. MRI was used to provide optimal visualization of the brain stem structures. The initial MRI performed at 4 weeks showed a mass in the dorsolateral aspect of the ponto-medullary junction of the brain stem with extension of edema into the right middle cerebellar peduncle. MRI studies at 4 and 7 months after onset showed a decrease in the overall size of the lesion, indicating resolution of edema and leaving behind a residual infarct cavity measuring approximately 5 mm in diameter (Figure 1). The lesion was centered in the dorsal medulla just anterior to the floor of the fourth ventricle and rostral to the obex. Esophageal motility studies were performed at 8 months after the neurological event (1 month after the last MRI and 1 month before a videofluoroscopic assessment) using 2 different manometric catheters and with a conventional water-perfused system. The first catheter contained 6 lumens with 5 recording apertures 5 cm apart and with the sixth aperture 3 cm proximal to the distal opening. With this manometric catheter, a “station pull through” technique was used to assess function of the UES and LES. The catheter was then positioned within the esophageal body such that the first aperture was 2 cm below the UES and the lowermost aperture was 2 cm above the LES. The second manometric catheter contained a “sleeve” assembly and was used to better characterize UES function. The “sleeve” was 2.5 cm in length. Recording apertures were also present at 0.5 and 2.5 cm above and 0.5 cm below the sleeve, and when the sleeve was correctly positioned across the UES, additional recordings could be obtained from the pharynx, esophageal body, and the LES. Using the first catheter assembly (Figure 2), the measured UES pressure varied from 20 to 130 mm Hg with respiratory fluctuation evident within the zone. With an attempted swallow, a distinct pharyngeal contraction wave was discerned proximally but was absent in the 1 cm above the UES. There was no effective relaxation of the UES. Furthermore, no definite contractile activity was present in the proximal 6 cm of the upper esophagus, the region corresponding primarily to striated esophageal muscle. Peristaltic contractions were evident in the more distal 15 cm of the esophageal body, the region corresponding primarily to smooth muscle esophagus. The mean LES pressure was normal and measured 36 mm Hg.
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Figure 1. MRI 7 months after presentation. (A ) T1- and (B) T2-weighted axial images and a (C ) T1-weighted sagittal image show an infarct cavity confined to a small region of the dorsolateral medulla just anterior to the floor of the fourth ventricle and rostral to the obex.
The LES relaxation-contraction sequence in response to the swallow was normal in appearance. Using the “sleeve” catheter assembly (Figure 3), similar motility information was obtained with more detail in the pharyngoesophageal region. In response to a swallow, a discrete pharyngeal contraction was evident 2.5 cm above the UES, but there was no swallow activity at the level of the UES or in the pharynx just above or the upper esophagus just below the UES. The mean basal UES pressure was 44 mm Hg. Esophageal contractile activity measured at a distance 8 cm below the sleeve sensor was normal. LES function was again shown to be intact.
Discussion In this patient, the matured lateral medullary syndrome was associated with a very specific form of dysphagia. The reflex pharyngeal and esophageal components of the swallow were initiated, and the oral and proximal portions of the pharyngeal swallow were intact. Adequate elevation of the posterior tongue and larynx were also stimulated with minimal conscious effort by the patient. However, although the UES had significant resting tone, the UES failed to relax and contract, and the striated muscles of the distal pharynx and proximal
esophagus failed to contract as part of the swallow response. On the other hand, the remainder of the swallow in the esophageal body, including the smooth muscle portion and LES, appeared to be intact and functioned normally. This pattern of motor abnormalities could be explained anatomically by a selective lesion involving primarily the neural elements connecting the circuitry of the central pattern generator (CPG), which controls swallowing and resides more dorsally and medially in the brain stem, to the region of the nucleus ambiguus (NA) supplying efferent motor fibers to the unresponsive areas. The NA is situated deeper and more laterally in the brain stem (Figure 4). Although the initial clinical picture and MRI findings indicated more extensive brain stem involvement, the later MRI findings on recovery would fit with this hypothesis. Furthermore, the combined findings lend support to the present concepts of how major brain stem elements interact to produce the sequential activation of the swallowing musculature. These concepts have arisen in large part from animal studies in sheep and rats in which the esophagus is virtually all striated muscle and the cat, which has a portion of the
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ing control mechanism, the “swallowing center,” is bilaterally represented by connected halves located in the medulla. Jean6,12 and Kessler13 have provided evidence for 2 levels of integration within the swallowing center.6,12,13 One level of integration (dorsal) is involved in the initiation of swallowing and the organization of the entire swallowing sequence, whereas a second level of organization (ventral) appears to serve primarily as a connecting pathway to the various motor pools involved in the swallowing sequence. Afferent information from the periphery enters into the NTS (dorsal), the afferent reception portal of the swallowing center to synapse on “premotor neurons.” This sensory information can initiate deglutition and the swallowing sequence, alter previously initiated activity in the swallowing center, and therefore modify ongoing motor activity. The esophageal premotor neurons also receive input from pharyngeal premotor neurons in the intermediate and interstitial
Figure 2. Esophageal motility recording with 6-lumen perfused catheter system. The proximal recording site is 2 cm below the UES, and the distal site is 2 cm above the LES. Note absence of contraction just below the UES and presence of a peristaltic contraction through the distal two thirds of the esophagus. Sw, swallow.
distal esophagus composed of smooth muscle as in the human. A proposed overview of some main brain stem structures, their connections, the direction of sequential activation, and the potential site of the lesion in the patient are diagrammed in Figure 5. Present concepts picture the CPG for swallowing and activation of the muscles of deglutition as a serial network of linked neurons within the nucleus of the solitary tract (NTS) and neighboring reticular formation, such that once activated, its rostrocaudal organization produces sequential excitation of motor neurons serving muscles along the deglutition pathway.6 – 8 At least 2 subnetworks are considered to be present, one for the oropharyngeal phase and the other in the subnucleus centralis for the esophageal phase of swallowing.9,10 Even segmental subcircuits have been suggested for the striated muscle portion.11 Presumably a similar subnucleus subserves the smooth muscle esophagus via the dorsal motor nucleus of the vagus. Anatomically, the swallow-
Figure 3. Esophageal motility study with a 6-lumen perfused catheter system having a sleeve positioned in the UES. The proximal recording site is 3 cm above the sleeve. Note absence of relaxation and contraction in the UES and absence of contraction in the striated muscle of the pharynx just above the UES and the esophageal body just below the UES. Normal motor function is present in the esophageal body and LES below. Sw, swallow.
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Figure 4. Cross-section of human brain stem and proposed site of lesion. Functionally, the lesion is positioned to spare the dorsomedial structures that would contain the CPG for swallowing in the NTS and the neighboring reticular formation, the dorsal motor nucleus of the vagus (DMNV), which serves the smooth muscle esophagus and LES, and perhaps the NA, which serves the striated muscle of the pharynx, UES, and upper esophagus. However, the lesion is positioned to interrupt the connections between the CPG circuitry and the NA serving these latter regions. XII, hypoglossal nucleus; Vn, trigeminal nucleus; Vt, trigeminal tract.
subnuclei of the NTS and connect with third-order esophageal neurons in multiple nuclei of the reticular formation, including the parvocellular nucleus.10 The reticular formation nuclei contain interneurons that are active as part of the CPG control for swallowing and esophageal peristalsis.14,15 In our patient, the swallow could be initiated and progress through the entire sequence, excluding only the striated muscle of the UES and adjacent distal pharynx and proximal esophagus. Therefore, the NTS subnuclei that receive afferent information and connect with each other, along with the neighboring reticular formation elements that are also involved with programming the swallow sequence, appear to be spared by the lesion. However, motor output to the unresponsive areas was absent. Swallow-induced motor activity of the striated muscle of the pharynx, UES, and esophagus occurs via vagal efferents originating in the NA. In rats, there is a topographic subdivision within the NA such that efferents originating more rostrally innervate the pharyngeal musculature, those fibers from neurons more medial and caudal innervate the striated muscle of the esophagus, and presumably fibers to the UES arise from in between.16 The persistent movements of the posterior tongue, proximal pharynx, and larynx in our patient
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indicate a sparing of the more rostral NA and its connections to the swallowing control mechanism. The presence of resting tone in the UES suggests that the NA motor neurons supplying this region are in fact also functional on the affected or unaffected side. These neurons are normally tonically active and are inhibited first and then activate forcefully as part of the programmed swallow sequence.17,18 They and the motor neurons to the pharynx and striated muscle esophagus can be activated by a direct paucisynaptic pathway from the cortex and via stimulation of the vagus or other cranial nerves.13,19,20 Furthermore, the UES tone decreases during sleep in the relative absence of swallowing.21 Therefore, other inputs to these neurons can apparently operate independent of the swallowing CPG. Absence of the normal swallow-induced relaxation and contraction of the UES, along with absence of contraction in the adjacent pharyngeal and esophageal striated muscle, is con-
Figure 5. Overview of brain stem control mechanism for swallowing and proposed site of lesion. Functionally, the lesion is positioned to interrupt the connections between the CPG circuitry for swallowing in the NTS and the neighboring reticular formation and the NA region, which serves the striated muscle of the pharynx, UES, and upper esophagus. The CPG and its series of subnuclei within the NTS, the NA, and the dorsal motor nucleus of the vagus (DMNV), which serves the smooth muscle esophagus and LES, are largely unaffected.
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sistent with damage primarily to the second (ventral) level of organization that acts as a connecting pathway to the NA neurons serving these regions during the swallowing sequence. Motor neurons to the smooth muscle esophagus, including the LES, are located in two subregions of the dorsal motor nucleus of the vagus. This nucleus lies in the central gray matter of the medulla and is lateral to the hypoglossal nerve and dorsal to the NA.22 Evidence from studies of the cat LES suggests that the rostral region contains neurons that mediate excitation and the caudal region neurons that mediate inhibition of the esophagus.23 The documentation of coordinated activity of the smooth muscle esophagus and LES in the patient indicates that the motor nucleus for this region (dorsal motor nucleus of the vagus), its connections to the brain stem circuitry that controls the entire ordered sequence of the swallow (NTS and neighboring reticular formation), and this circuitry itself are in large part intact and functional. In this patient, a lesion apparently localized to one side of the brain stem has caused significant neuromuscular dysfunction and dysphagia, although the mechanism for control of swallowing is bilaterally represented in the medulla. Similar observations have been made in other patients with brain stem vascular accidents.2,24,25 These investigators explain the finding by visualizing the requirement for integrated bilateral control that will be disrupted by a lesion on only one side. However, in the face of destruction of the region of the CPG on one side, stimulation to the opposite intact side can result in the entire swallow sequence.7 Therefore, maintenance of the swallow sequence in this patient suggests that, as elsewhere in the brain, there is functional asymmetry and unilateral damage to the dominant side will produce functional abnormality, while unilateral involvement of the nondominant side will have little or no effect on function. This type of asymmetry is well described for regions of the cortex involved with the induction of swallowing, with the subsequent recovery from a unilateral stroke with dysphagia being associated with enhancement of function on the nondominant cortical hemisphere.26,27 Some of the dysphagia that occurs intermittently with cervical spine surgery has also been attributed to functional asymmetry.28
Summary The assessment of dysphagia in a patient with lateral medullary syndrome has provided insight into and support for the present concepts of the central brain stem control of swallowing. The findings indicate that this
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control in humans is similar to that proposed and arising from animal studies.
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Received January 31, 2001. Accepted March 28, 2001. Address requests for reprints to: Rosemary Martino, M.A., M.Sc., Toronto Western Hospital, University Health Network, Department of Speech Language Pathology, Fell Pavilion, 4th floor, Room no. 171, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. e-mail: [email protected]; fax: (416) 603-6204. Supported by a grant from the Medical Research Council of Canada. The authors thank Phillip Collman for the figures.