Velocardiofacial syndrome (VCFS) is caused by a deletion 22q11.2 with clinical characteristics of mild facial dysmorphia, palatal anomaly, conotruncal cardiac defect, immunodeficiency, and hypocalcaemia (1). VCFS often presents with feeding difficulties early in life (2–4); however, there is a poor understanding of the pathophysiology of the observed feeding and swallowing disorders.
Bolus flow through the pharyngo-oesophageal segment is clearly disrupted and the effectiveness of bolus propulsion, pharyngeal contraction, and upper oesophageal sphincter (UOS) relaxation may well be abnormal. Current radiologic methods cannot easily distinguish between these features, so we combined radiology with high-resolution manometry to record the degree and patterning of pharyngeal and UOS squeeze on an intraluminal catheter positioned along the pharyngo-oesophageal segment. We report our findings in 3 children with VCFS and persistent severe feeding difficulties despite previous investigations and therapeutic attempts.
A combined high-resolution videomanometry technique (HRVM) allowed accurate assessment of dynamic pressure changes within the bolus, as well as those caused by luminal closure following contraction of the pharynx and UOS. Pressures were visualised and interpreted in the form of a “space time plot,” a map of pressure plotted against both time and spatial location using the Trace! v1.2 videomanometry system (Hebbard G, Royal Melbourne Hospital, Melbourne, Australia).
Approximately 30 minutes before HRVM, a 12-channel recording manometry catheter was passed transnasally and positioned straddling the UOS. After the child adjusted to the catheter, the patient was taken to the fluoroscopy suite for HRVM. The position of the catheter across the UOS was verified fluoroscopically and manometrically. The speech pathologist offered boluses of different consistency to swallow, depending on the child's regular diet. Nutritive swallows were recorded during video runs of 5 to 20 seconds each. Multiple boluses of the same volume were offered to each child varying from 1 to 3 mL depending on the age and oral skills of the child.
The manometric recordings were analysed for the following standard manometric measures of swallowing: basal UOS pressure, UOS relaxation interval, UOS relaxation nadir pressure, pharyngeal peak pressure, pharyngeal contraction velocity, and pharyngeal intrabolus pressure. A manometric diagnosis of the cause of swallowing dysfunction was achieved by comparing the characteristics of swallowing determined in individual patients with laboratory normative data. The normative data was derived from children referred for videofluoroscopy (VF) not demonstrating any swallowing abnormality or aspiration during investigation.
A 2-year-old girl with VCFS was referred with severe dysphagia, significant gagging, and profuse salivary secretions with the attendant risk of aspiration. Major feeding difficulties at 6 months of age led to a Nissen fundoplication and percutaneous endoscopic gastrostomy.
A VF at 14 months showed pooling of bolus in the valleculae, lack of UOS opening, a cricopharyngeal bar resulting in a thin trickle of contrast into the oesophagus, and significant nasal regurgitation, but no aspiration. Three consecutive balloon dilations of the UOS up to 12 mm were performed without lasting effect. The exact cause of the UOS dysfunction and her dysphagia remained unclear. At the time of referral, she was not tolerating nasogastric feeds and waking hourly at night coughing with copious secretions requiring frequent suction.
During the feeding observation, she experienced severe respiratory distress and needed suction on a semisolid (yogurt) and liquid bolus of 1 to 3 mL.
An HRVM study was carried out with a liquid and semisolid bolus studied in the lateral view. Because of the high distress and severe aspiration risk, only 1 bolus of each consistency was administered.
Oral phase of swallowing was normal. During the pharyngeal phase, normal swallowing was triggered at the level of the tongue base and with adequate velopharyngeal closure, laryngeal elevation, and closure. Ventral movement of the posterior pharyngeal wall was well timed and clearly present. There was laryngeal penetration, but no aspiration. Despite multiple ineffective swallows, the bolus pooled at the level of the piriform sinus with subsequent retrograde bolus flow into the nasopharynx at the time of the initiation of pharyngeal swallow. Postswallow residue that needed to be suctioned was observed in the hypopharynx. The UOS stayed closed; no cricopharyngeal bar was documented.
The manometric trace showed an abnormal UOS resting pressure of 63to 99 mmHg. During swallowing, the UOS failed to relax and maintained a higher than normal residual pressure of 25 to 75 mmHg. In contrast, the pharyngeal pressure wave sequences were propagated in an antegrade direction with normal amplitudes of 31 to 48 mmHg. Figure 1 shows a normal swallow (Figure 1A) and an example of this child's typical swallow pattern (Figure 1B).
Conclusions and Recommendations Based on Combined VF and HRVM
Bolus propulsion and pharyngeal contraction were normal, but the pressures generated were insufficient to overcome the residual pressure of the poorly relaxing UOS. This led to bolus pooling in the piriform sinus and retrograde escape of the bolus with initiation of the pharyngeal stripping wave confirming a diagnosis of UOS achalasia. A chest computed-tomographic scan revealed bronchiectasis. The recommendation was to stop oral feeding, because the UOS dilatation brought only temporary (up to 2 weeks) relief. Botulinum toxin A injection under direct electromyographic surveillance led to marked improvement, removal of suction, and introduction of oral feeds.
A 20-month-old girl with VCFS was referred because of severe dysphagia. A gastrostomy was inserted at age 6 months and a soft-palate cleft repaired 1 month later. She continued to have chest infections. A previous VF showed incoordination of the swallow, delayed pharyngeal clearance, pooling in the piriform sinus above the UOS, a cricopharyngeal bar, and silent aspiration. The medical team suggested tracheal reconstruction with tracheostomy and Nissen fundoplication, but the child was referred for further assessment.
Oral motor function showed limited tongue movement in anterior-posterior direction, but no pathological oral reflexes. She accepted a semisolid (avocado) and a liquid (1 mL) bolus administered by syringe in the buccal cheek leading to gargling, more obvious with thin fluids. No suction was needed. VF and HRVM were performed similar to case study 1, using a thin liquid, a thickened liquid, and semisolid bolus in lateral view.
The oral phase showed inadequate bolus propulsion due to insufficient posterior movement of the tongue base and delayed oral transit time of 2 to 4 seconds (normal: 1 second).
The pharyngeal phase showed the swallow was triggered at the level of the piriform sinus, which is considered delayed, and inadequate velopharyngeal closure due to insufficient elevation of the repaired soft palate. Ventral movement of the posterior pharyngeal wall was inconsistent. Thin liquid bolus led to laryngeal penetration and aspiration during and after the swallow. A delayed cough was insufficient to fully clear the airway. No aspiration occurred on thickened liquid and semisolid boluses. The child needed multiple swallows to clear the bolus, but most swallows were ineffective leading to postswallow residue at the level of the hypopharynx.
In the oesophageal phase, the duration of UOS opening was too short, with only partial bolus passage through the UOS. The bolus head was propagated into the proximal oesophagus, but the bolus tail pooled in the piriform sinus, or there was retrograde flow of the bolus tail via the posterior pharyngeal wall into the nasal cavity (Figure 1C). No cricopharyngeal bar was observed.
HRVM found normal peak amplitudes of the pharyngeal pressure sequence (48–66 mmHg) that were synchronous instead of antegrade. UOS resting pressure was normal (27–40 mmHg), but relaxed incompletely during swallowing. UOS relaxation was short (0.22 seconds) and, at the nadir of UOS relaxation, a residual pressure of 17 to 25 mmHg was recorded in 56% of the swallowed boluses. The premature closure of the UOS was due to a combination of incomplete and short UOS relaxation.
Conclusions and Recommendations Based on Combined VF and HRVM
The causes of this child's dysphagia were poor tongue propulsion; synchronous (instead of antegrade) pharyngeal contractions; short duration of UOS relaxation (leading to premature contraction of the sphincter on the bolus); and incomplete UOS relaxation. Unlike in case 1, the UOS did relax in a way that allowed bolus flow into the proximal oesophagus, but the relaxation process was short and inadequate, leading to bolus residues being trapped above the UOS. As with case 1, the presence of pharyngeal residues in association with a closed UOS led to retrograde escape of the bolus, with initiation of the pharyngeal stripping wave. The synchronous nature of the pharyngeal stripping wave probably exacerbated its ineffectiveness. We recommended temporarily suspending oral feeding with an oral stimulation program to maintain her oral skills. Based on the less severe nature of UOS dysfunction compared with case 1, UOS dilatation was considered over Botox (Allergan, Irvine, CA). When ready for oral feeding, this child would very likely benefit from “effortful swallow” training and from tongue-strengthening exercises. To date, no intervention has been implemented, and recent investigations showed ongoing dysphagia with aspiration.
A 3-year-old boy with VCFS was referred for further manometric assessment of his UOS function during swallowing because a previous VF showed insufficient cricopharyngeal opening. He presented with occasional unpredictable choking episodes, food cramming, gagging, and nasopharyngeal regurgitation.
His growth parameters were normal. Oral structures were hypotonic but functional. Pathological oral motor reflexes were not noted. He was a habitual mouth-breather related to his oral hypotonicity.
During clinical observation, he was keen to drink liquids from a cup with a spout, and ate crackers, chips, a sandwich, and a banana without any difficulty. He crammed his food, rather than emptying his mouth first. No nasal regurgitation was observed at his clinical assessment, although it was reported by the parents. The previous VF did not show aspiration and no respiratory disease was present, so VF was not repeated.
Pharyngeal and UOS manometry showed an antegrade pharyngeal-pressure sequence, but with peak pharyngeal amplitudes lower than normal on dry swallows (9–11 mmHg), increased with wet boluses (25–30 mmHg) to be within normal limits. The difference in amplitude between dry and wet boluses may indicate a hyposensitive pharynx. This manometric observation correlated with the clinical finding that he ate much better on boluses providing increased sensory information, such as larger volumes and foods with strong flavours.
The pharyngeal-pressure sequence was well coordinated, with normal UOS relaxation and resting pressures (32–61 mmHg). The UOS relaxation was complete and initiated peristalsis in the proximal oesophagus. However, periods of isolated high UOS amplitudes (71–181 mmHg) were observed during a feed, suggesting intermittent UOS spasm with a duration varying from 7 to 26 seconds. These events correlated with the clinical observation of the episodes of sudden food refusal. Although the UOS showed intermittent spasm, it relaxed appropriately in the majority of the swallows. Figure 1D shows an example of a UOS spasm as observed in case 3.
Conclusions and Recommendations Based on Combined VF and HRVM
The occasional choking problems were probably due to UOS spasm. Because of decreased pharyngeal sensitivity, we recommended offering foods with strong flavour, as well as alternating semisolids with liquids. No medical therapy was offered for the spasms, but we advised to allow time out when he refused food, not to force-feed it, and to offer food again after a few minutes. This strategy was successful.
Despite a similarity of primary pathology and presenting symptoms in all 3 cases, the manometric characteristics of the swallow disorder, as indicated by HRVM, differed. We were clearly able to recognise a range of severity in UOS dysfunction—a nonrelaxing UOS (achalasia), poorly relaxing UOS, and normally relaxing with intermittent UOS spasm—that suggests that a common underlying disorder of inhibitory nerves may be present in children with VCFS.
In our opinion, HRVM is an appropriate diagnostic tool to distinguish subtle differences between these different pathologies that may require different therapeutic interventions. Our experience differs from others, who state that manometry of the UOS and pharynx yields little information that changes the management of the patient with upper dysphagia (5,6). We take the view that the precise understanding of the nature of UOS dysfunction offered by HRVM is an important guide to therapeutic interventions such as UOS dilatation (7,8), Botox (9), and myotomy (10). We suggest that prolonged closure of the cricopharyngeal muscle on VF is not always an indication for surgical treatment such as myotomy. This is because a nonopening sphincter may be caused by a variety of dysfunctions—from achalasia to poor pharyngeal propulsion—that may not be obvious based on VF alone.
Nasal regurgitation of liquids during bottle or breast-feeding is a clinical indication for further assessment of palatal anatomy and function by VF, and it is usually assumed that VF-based findings of nasal regurgitation are indicative of palatal dysfunction. Children with VCFS are particularly prone to palatal abnormalities such as velopharyngeal insufficiency (3,11), which leads to nasal regurgitation during swallowing due to the bolus being forced into the nasal cavity. Eicher et al (4), however, observed that retrograde flow can be present in children with VCFS without palatal involvement because of pharyngeal and UOS dysfunction. Our observations from cases 1 and 2 support this; failure of UOS relaxation with or without pharyngeal dysfunction was associated with retrograde flow and nasal regurgitation. A VF-based observation of retrograde flow and nasal regurgitation should not automatically lead to the diagnosis of velopharyngeal insufficiency.
These case studies clearly illustrate the value of HRVM in identifying the precise cause of abnormal bolus flow during swallowing. We believe that this may assist with early diagnosis and improved accuracy of clinical assessment, lead to more effective treatment of swallowing disorders, and prevent secondary feeding behavioural problems in the longer term.
We extend special thanks to Sue Olivieri of the Centre for Paediatric & Adolescent Gastroenterology, and to Deb Balmond and all of the nursing staff in the Department of Medical Imaging, for their expertise and the excellent collaboration. We also would like to thank the parents of the 3 children for their cooperation, as well as Dr Ted O'Loughlin of Westmead Children's Hospital in Sydney and Prof Ian Cook of St. George Hospital in Sydney for referring these patients to the centre.
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