Paraplegia 31 (1993) 384-392 © 1993 International Medical Society of Paraplegia
Esophagitis and esophageal motor abnormalities in patients with chronic spinal cord injuries
J G Stinneford MD, A Keshavarzian MD, B A Nemchausky MD, M I Doria MD, M Durkin MD Departments of Medicine and Pharmacology, Loyola University Medical Center, Maywood, Illinois; Medical, Spinal Cord Injury and Pathology Services, Hines Veterans Hospital, Hines, Illinois, USA.
To investigate the frequency and severity of esophagitis and esophageal dys motility in patients with chronic spinal cord injury (SCI), 46 males with chronic SCI completed a questionnaire regarding gastrointestinal symptomatology. Eleven of these patients subsequently underwent upper gastrointestinal (GI) endoscopy with esophageal biopsies and 10 of the 11 also had esophageal motility studies. A significantly higher percentage of SCI patients experienced heartburn (SCI 61% ; controls (C) 40% ), esophageal chest pain (SCI 33% ; C 6.4%), and intermittent dysphagia (SCI 30% ; C 8.5%). Forty-five percent of SCI patients had endoscopic evidence of mild esophagitis, and 91 % of them had histologic evidence of esophagitis. SCI patients had low amplitude, slowly propagating abnormal (double-peaked) peri static esophageal contractions. We conclude that SCI patients experience significantly more esophageal symptoms than controls. They have a higher incidence of esophagitis and esophageal motor abnormalities. The clinical relevance of these abnormalities remains to be evaluated.
Keywords: spinal cord injury; reflux esophagitis; esophageal motor abnormalities; gastrointestinal symptomatology.
Introduction sociated complications. Recent studies have demonstrated an increased incidence of Spinal cord injuries (SCI) represent a signi abnormalities in the upper gastrointestinal ficant worldwide health problem, most tract, particularly gastric and duodenal often affecting young, otherwise healthy ulceration, erosions and bleeding.5-9 These individuals. Historically, a spinal cord injury disorders may produce greater morbidity meant a rapid, progressive downhill course because severe cord injury can alter somatic with death ensuing secondary to pulmonary, perception thereby delaying diagnosis and urinary or infectious complications.1-3 For therapy.6,7,9 One might also expect patients tunately, advances in the management of with SCI to be at a greater risk for esopha the acute injury have led to a marked geal disease, A number of factors may decline in overall mortality since World War predispose these individuals to gastro II.3,4 However, inherent in this longevity is esophageal reflux with its associated seque the subsequent development of related co lae, First, they spend a greater proportion of morbid disease which can significantly alter time in the supine or semi-upright position. the quality of life. Second, esophageal motor abnormalities One area of concern in this population is have been described in other patient groups chronic gastrointestinal dysfunction and as- suffering from chronic myelopathies 10 and if present may diminish acid clearance, Third, the majority of these patients will demons Correspondence: Ali Keshavarzian MD, Associate Professor of Medicine, Section of Gastroenterology, trate increased intraabdominal pressure Loyola UnIversity Medical Center, 2160 South First more frequently because of chronic Avenue, Maywood, IL 60153, USA. constipation, frequent valsalva maneuvers Paraplegia 31 (1993) 384-392 Esophagus and chronic spinal cord injury 385 and use of abdominal musculature for trans (defined as food related and/or relieved fers. Esophageal function and disease in with antacids), fullness after meals and spinal cord injured patients has not previ abdominal pain. A severity index was cal ously been systemically evaluated. culated using the product of the frequency For these reasons we designed a study of a given symptom per week and its with the following aims: (1) to determine severi ty (assessed by a visual analog of the frequency of gastrointestinal and 0-10). Each patient was asked whether he esophageal complaints following long-stand had a given symptom (regardless of its ing spinal cord injury; (2) to determine severity) during the last year. If the answer whether patients with chronic stable spinal was positive, then he was asked to deter cord injuries have a higher incidence of mine the frequency of the episodes of the esophagitis and, if so, to delineate the symptom (regardless of the duration of extent and severity of the inflammation; and severity) per week. Then he was asked to (3) to assess esophageal motor function in indicate the severity of the symptom this population. (regardless of its frequency) by marking on a 10 cm graduated line. The questionnaire was administered to each and every patient Methods and patients by one of the authors (JGS). Patient population Subjects consisted of male patients admitted Assessment of esophagitis to the SCI service of Hines Veterans Hos Upper GI endoscopy (EGD) was performed pital. All of the SCI were greater than one on 11 male volunteers with chronic SCI as year in duration and all were judged to be defined above (age range 25-60); mean 50.5 neurologically stable. None of the subjects yrs). These subjects were similar to the had been admitted to the unit for problems remaining 32 patients with regard to age as related to the gastrointestinal tract. SCI well as frequency and severity of GI symp levels ranged from C5 to TlO. Subjects were toms (Table I). The results were compared excluded if they suffered from illnesses with 18 asymptomatic males admitted to known to alter gastroesophageal motor the Veterans Administration alcohol detoxi function such as diabetes mellitus or fication unit (age range 31-60; mean 44 scleroderma or if they required chronic yrs). These alcoholic controls happened to medication known to affect GI motility have no esophageal symptoms regularly (including benzodiazapines and anticholin (monthly) at the time of the EGD. Their ergics). A questionnaire was given to 46 last alcoholic drink was at least 3 days consecutive SCI patients and following its (range 3-14 days) prior to the EGD. Prior completion all were asked to undergo to undergoing EGD all subjects were asked esophagogastroduodenoscopy (EGD) and to fast overnight. Intravenous sedation was esophageal motility testing. Eleven of the 46 achieved with midazolam (Roche Laborat agreed to participate in endoscopy and 10 of ories, Nutley, NJ). The oropharynx was the 11 agreed to undergo motility studies. anesthetized with tetracaine applied topic ally. An Olympus GIFXQlO endoscope Questionnaire (Olympus, Lake Success, NY) was utilized A detailed questionnaire was administered and three forceps pinch biopsies were ob to 46 consecutive SCI males in order to tained at each of two sites 2 cm and 5 cm quantify the nature and intensity of any above the gastroesophageal junction. Endo long-standing GI symptomatology. Data scopic appearance was graded according to were compared with 47 male controls of previously published criteria. 11 The grading similar ages admitted to the Veterans Hos scale was as follows: grade 0, no mucosal pital with medical problems unrelated to the abnormalities; grade 1, no macroscopic ero GI tract. GI complaints evaluated included sions but erythema, hyperemia, or mucosal frequency of defecation as well as presence friability; grade 2, superficial erosions in and severity of heartburn, nausea, vomiting, volving < 10% of the mucosal surface of the dysphagia, chest pain of esophageal origin last 5 cm of esophageal squamous mucosa; 386 Stinneford et al Paraplegia 31 (1993) 384-392
grade 3, superficial erosions or ulceration involving 10-50% of the mucosal surface of the last 5 cm of esophageal sqaumous mu cosa; grade 4, deep peptic ulceration any where in the esophagus or confluent erosion of > 50% of the mucosal surface of the last 5 cm of esophageal squamous mucosa. All three biopsy specimens from each of two sites were oriented on filter paper and histologic evaluation was performed by an investigator blinded to the endoscopic find ings. The presence of histologic esophagitis was assessed according to previously re ported criteria.12-14 Esophagitis was con sidered to be present if both the basal cell layer and papillae were hypertrophied to greater than 50% of the specimen thickness. - The presence of neutrophils in the lamina IZI propria was considered to be supportive evidence of esophagitis.
Assessment of esophageal motility Ten of the 11 SCI subjects evaluated for reflux esophagitis also underwent esopha geal manometry. One subject refused further investigation. These data were com pared with a control group which consisted of 13 healthy male asymptomatic volunteers (age range 24-39; mean 31 yrs). Esophageal manometry was performed utilizing an eight-lumen esophageal catheter with a 6 cm - Dent sleeve and high-pressure, low-com IZI pliance infusion system (Arndorfer Medical Specialists Inc, Greendale, WI). Intra luminal pressures were transmitted by water-filled catheters to external trans ducers (Sensormedics Transducers and Dynograph, Anaheim, CA). The recording catheters were arranged to measure pres sure through side orifices, spaced at 3 cm intervals. The infusion rate was 0.5 ml/min at each orifice. Sensitivity of the system was 400 mmHg/s. Lower esophageal sphincter pressure (LESP) was measured by a Dent sleeve. Intragastric pressure was continu ously measured by a catheter distal to the sleeve and LESP was measured against intragastric pressure which was considered to have a value of zero. Peristaltic amp litude, duration and velocity in response to wet swallows (5 ml intraoral water bolus) at 30-second intervals were assessed at 3 cm, 6 cm and 9 cm above the LES. Paraplegia 31 (1993) 384-392 Esophagus and chronic spinal cord injury 387
Statistical analysis of SCI patients reported heartburn, dys The statistical significance of the results was phagia, esophageal chest pain and abdom assessed by the Mann-Whitney U test when inal pain. In addition, their symptoms were GI symptomatology/symptom indexes were significantly more frequent and more severe compared between SCI patients and con than controls (Table III). Eleven of 28 trols, and chi-square when the frequency of symptomatic SCI patients (39% ) had symptoms were compared. The frequency weekly heartburn and 20 patients (71% ) had of esophagitis was compared utilizing the monthly heartburn. In contrast, only 3 chi-square test and differences in motility (16% ) and 9 (47% ) of symptomatic controls results were analyzed with Student's t test. had weekly and monthly heartburn respect A probability value of < 0.05 was con ively. Similarly, 7 (47%) and 9 of 15 (60%) sidered significant. symptomatic SCI patients had weekly and monthly esophageal chest pain respectively; while one of 3 symptomatic controls had weekly chest pain. Frequent abdominal pain Results was also significantly more common in Frequency and severity of gastrointestinal symptomatic SCI patients: 17 of 24 (71% ) symptoms had weekly pain and 20 (83% ) had monthly Patients with chronic SCI reported a signi pain. Monthly abdominal pain was reported ficantly higher number of GI complaints by 3 controls. when compared to controls, especially with Nausea, vomiting and postprandial full regard to esophageal symptomatology ness were not significantly different between (Table II). A significantly higher percentage the two groups. None of the 46 SCI patients
Table II Frequency of GI symptoms in patients with spinal cord injury (SCI)
Heartburn Esophageal chest pain Abdominal pain Dysphagia frequency frequency frequency frequency
SCI patients 28/46" 15/46" 24/46" 14/46" (n = 46) (61%) (33%) (52%) (30%) Controls 19/47 3/47 4/47 4/47 (n = 47) (40%) (6. 4%) (8. 5%) (8. 5%)
Significantly higher numbers of patients with spinal cord injuries (SCI) reported episodes of heartburn, esophageal chest pain and dysphagia than control groups. Frequency = number of patients experiencing the symptom. "p < 0. 05 SCI patients versus controls.
Table III Severity of GI symptoms in patients with spinal cord injury (SCI)
Heartburn Esophageal chest pain Abdominal pain
Frequency SI Frequency SI Frequency SI of episodes of episodes of episodes
SCI patients 1. 3" 7. 2" 1. 3" 4. 6" 3. 1" 16.2" (n = 46) Controls 0. 4 5. 8 0. 4 2. 4 0. 7 4. 8 (n = 47)
Patients with SCI reported significantly more severe and more frequent episodes of heartburn, chest pain, and abdominal pain. SI = severity index = frequency/week x visual analog scale. Frequency of episodes = number of symptom episodes per week. "p < 0. 05 SCI patients versus control subjects. 388 Stinneford et al Paraplegia 31 (1993) 384-392 had spontaneous bowel movements and 100 Frequency of endoscopic esophagitis each required a specific program of bowel care to minimize constipation. 80
"if2. 60 6/11 Assessment of esophagitis � C In the SCI group 91% (10 of 11) demons QJ 40 4111 trated histologic evidence of significant .� a... esophagitis compared to 6% (1 of 18) of 20 asymptomatic controls (Fig 1). Every SCI 1/11 patient judged to have reflux esophagitis 0 I I met all three histologic criteria in at least Grade 0 Grade 1 Grade 2 one biopsy specimen. The endoscopic find ings did not correlate well with the histo Figure 2 Endoscopic grading of esophageal mu logic evaluation. One subject received an cosa in spinal cord injured patients correlated poorly with histologic findings. endoscopic score of 2 and 4 additional subjects received a score of 1. The remain ing 6 had normal appearing esophageal mucosa (Fig 2). No esophageal stricture was noted in any of the patients studied. None of Amplitude of esophageal contractions the 18 control subjects demonstrated endo in patients with spinal cord injury scopic evidence of esophagitis. 100 Cf) w --' 80 QJ Assessment of esophageal motility > 0- The esophageal contraction amplitude .g!t 60 (ECA) in SCI patients was significantly E E u E 40 lower than in controls when measured at en - 9 cm and 6 cm above the LES (Fig 3). ECA co 20 0.1...---'----'---- '--- Controls SCI Figure 4 Th e esophageal contraction velocity was significantly slower proximally in spinal cord injured patients. No difference was noted in the distal esophagus. W \D 0 V, ::to ;:: Table IV Demographic characteristics and esophageal findings in patients with spinal cord injury (SC I) ;:: � 0 Patient Age Level of Esophageal Histologic Macroscopic LESP Esophageal Esophageal i1 '" injury symptoms" esophagitis grading (mmHg) contraction contraction .... amplitudeb velocity !2.. (mmHg) (9 to 6 cm/s) 1 48 T4-5 H Yes 1 14 6cm = 75 4.7 9 cm = 41 2 57 no None Yes 1 23 6cm = 43 9cm = 43 3 54 C5-6 None Yes 0 18 6cm = 37 2.9 9 cm = 25 4 25 C5-6 H,D,E Yes 20 6cm = 59 1.4 9cm = 64 5 32 T5-6 H,A Yes 2 16 6cm = 56 4.6 9cm = 26 6 56 T5-6 H,D,E,A Yes 0 12 6cm = 32 1 9cm = 30 7 58 T9 H,D,E Yes 0 13 6cm = 35 3.2 9cm = 48 8 60 TI-3 D,A Yes 0 13 6cm = 30 5 9cm = 10 9 57 C5-6 H,A Yes 0 14 6cm = 31 3 9cm = 27 17 6cm = 48 10 58 C5-6 A Yes 0 1. 5 "tl '" 9 cm = 58 .... 11 66 T5-6 None No 0 ND ND ND {l � Ei' aH = heartburn, D = dysphagia, E = esophageal chest pain, A = acid reflux. b Amplitude and velocity of esophageal contraction measured at ...... 6cm and 9 cm above LES; normal: 9 cm = 74 ± 11 mmHg, 6 cm = 85 ± 6 mmHg, 9 to 6cm = 4.2 ± 0.3 cm/s. LESP = lower esophageal sphincter - '-0 pressure. ND = not done. '-0 � w 00 .jo>. I w '-0 N Paraplegia 31 (1993) 384-392 Esophagus and chronic spinal cord injury 39 1 TLESR in both normals and patients with trated a higher frequency of abnormal con documented reflux when intragastric pres tractions which may contribute to overall sure was increased with balloon disten peristaltic dysfunction. Similar esophageal sion.1s These findings would appear to be motor disturbances have been described in significant in the setting of a chronic SCI patients with GERD.17 These abnormalities because, as stated in the introduction, these may increase the acid exposure time, but patients demonstrate frequent episodes of direct measurement of acid clearance in the increased intraabdominal pressure. This el SCI population is necessary for confirma evation in intraabdominal pressure could, tion. therefore, predispose these patients to more It is also possible that these motor abnor frequent TLESR with the subsequent reflux malities are a consequence of reflux disease of gastric contents into the esophageal rather than causative. Our study cannot lumen. This concept is supported by the exclude this possibility since our control observations of Gore and coworkers who subjects had no esophagitis. Further studies noted an increased frequency of gastroeso are needed to compare esophageal motility phageal reflux in SCI patients undergoing SCI patients with esophagitis with SCI barium studies. 5 However, studies with patients without esophagitis. 24-hour esophageal pH measurement is The LESP and percent LES relaxation needed to determine whether gastroeso were normal in our SCI group. This is not phageal reflux is more frequent or more unexpected given the fact that vagal in severe in these patients. We initially nervation remains intact in the majority of planned to perform 24-hour pH studies in cord injuries. our patients. Unfortunately, none of our Interestingly, chronic SCI patients did not patients agreed to undergo such a test. experience more nausea, vomiting or post Another important pathophysiologic prandial fullness implying that clinically component of reflux esophagitis is the significant gastric dysmotility may not be length of exposure of esophageal mucosa to present in the majority of SCI patients. This gastric contents. Studies have shown that is supported by a recent study demonstrat esophageal acid clearance is dependent on ing normal gastric emptying in chronic SCI normal primary peristaltic function (volume patients. 21 clearance) and acid neutralization with sal Finally, the endoscopic mucosal grading ivary bicarbonate.19 Kahrilas et at demon correlated poorly with the presence or strated a positive correlation between peri absence of histologic esophagitis in our staltic dysfunction and ineffective volume study. This is not surprising and is consistent clearance from the esophageal lumen.2o with other studies comparing endoscopic Therefore, esophageal dysmotility may in appearance to histologic evaluation, espe crease the risk of reflux esophagitis by cially when the inflammatory changes are diminishing acid clearance. 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