Veterinary Surgery 39:139–149, 2010
Esophageal Dysfunction in Dogs with Idiopathic Laryngeal Paralysis: A Controlled Cohort Study BRYDEN J. STANLEY, BVMS, MVetSc, Diplomate ACVS, JOE G. HAUPTMAN, DVM, MS, Diplomate ACVS, MICHELE C. FRITZ, BSc, LVT, DIANA S. ROSENSTEIN, DVM, MS, Diplomate ACVR, and JENNIFER KINNS, VetMB, MRCVS, Diplomate ACVR, Diplomate ECVDI
Objectives—To compare esophageal function in dogs with idiopathic laryngeal paralysis (ILP) to age and breed matched controls; to determine if dysfunction is associated with aspiration pneumonia over 1 year; and to compare clinical neurologic examination of dogs with ILP at enrollment and at 1 year. Study Design—Prospective controlled cohort study. Animals—Dogs with ILP (n ¼ 32) and 34 age and breed matched healthy dogs. Methods—Mean esophageal score was determined for each phase of 3 phase esophagrams, analyzed blindly. After unilateral cricoarytenoid laryngoplasty, dogs with ILP were reexamined (including thoracic radiography) at 1, 3, 6, and 12 months. Neurologic status was recorded at enrollment, 6 and 12 months. Results—Esophagram scores in dogs with ILP were significantly higher in each phase compared with controls, most notably with liquid (Po.0001). Dysfunction was more pronounced in the cervical and cranial thoracic esophagus. Five dogs that had aspiration pneumonia during the study had significantly higher esophagram scores than dogs that did not develop aspiration pneumonia (Po.02). Ten (31%) ILP dogs had generalized neurologic signs on enrollment and all ILP dogs developed neurologic signs by 1 year (Po.0001). Conclusions—Dogs with ILP also have esophageal dysfunction. Postoperative aspiration pneumonia is more likely in dogs with higher esophagram scores. Dogs with ILP will most likely develop generalized neuropathy over the course of 1 year. Clinical Relevance—Esophagrams and neurologic examinations should be performed on all dogs with ILP. r Copyright 2010 by The American College of Veterinary Surgeons
in Bouviers des Flandres, Siberian husky, and Siberian husky mixed breed dogs.5–7 Other proven or presumed hereditary laryngeal paralyses, some associated with polyneuropathies, have been reported in young Dalmatians, Rottweilers, Pyrenean mountain dogs, Leonberger dogs, and white-coated German shepherd dogs.8–15 Laryngeal paralysis can be acquired from specific traumatic, neoplastic, and iatrogenic processes, and has been associated inconsistently with hypothyroidism, myasthenia gravis and generalized neuromuscular disease.4,16–23
INTRODUCTION
C
ANINE ACQUIRED idiopathic laryngeal paralysis (ILP) is a common condition affecting older, usually large-breed dogs, in which almost all of the intrinsic muscles of the larynx become paralyzed.1–4 It is an insidiously progressive disease with high morbidity, where affected dogs develop signs of upper airway obstruction, often becoming severely compromised. Congenital hereditary forms of laryngeal paralysis have been described
From the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI. Corresponding author: Bryden Stanley BVMS, Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824. E-mail: stanle32@cvm.msu.edu. Submitted March 2009; Accepted June 2009 r Copyright 2010 by The American College of Veterinary Surgeons 0161-3499/09 doi:10.1111/j.1532-950X.2009.00626.x
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Typically, in affected older dogs, a specific cause is not identified and the term ‘‘idiopathic laryngeal paralysis’’ is used as the accepted diagnosis.21,24–29 ILP has been characterized as a neurogenic atrophy of the laryngeal muscles because of progressive degeneration of the recurrent laryngeal nerves (RLNs).1,30 Both RLNs arise from their respective vagus nerves in the cranial half of the thorax and terminate as the caudal laryngeal nerves, providing motor innervation to all of the intrinsic laryngeal muscles except the cricothyroideus muscle, which is innervated by the external branch of the cranial laryngeal nerve.31 The most obvious clinical sign of ILP, life threatening respiratory distress, occurs because the arytenoid cartilages remain in a flaccid paramedian position and cannot effectively abduct. The resultant increased resistance to airflow and increased turbulence through the rima glottidis causes stridor, intolerance to exercise, and exacerbates respiratory distress. Further, inability to actively adduct the glottis during deglutition requires the epiglottis (which moves caudally, passively, upon swallowing) to provide primary protection from aspiration in these dogs. Unilateral crico- or thyroarytenoid laryngoplasty is commonly performed to alleviate clinical signs28,32–43 by fixing 1 arytenoid cartilage in a variably abducted position to permanently enlarge the rima glottidis.23,36–38,41 Reported incidences of postoperative complications for unilateral laryngoplasties are high, ranging from 28% to 56%, with aspiration pneumonia being the most important complication.22,27,40 Postoperative aspiration pneumonia has been attributed to the surgical procedure, which renders the airway more susceptible to laryngotracheal aspiration. A rarely cited pair of nerves, the pararecurrent laryngeal nerves (pRLNs), branch off the RLNs as they arise from the vagus nerve and run parallel and dorsal to the RLNs, supplying the cervical and cranial thoracic esophagus, and trachea.44–49 It has been well established that the RLNs degenerate in ILP. Because of the common origin of the RLNs and the pRLNs, it is possible that the pRLNs may also be similarly degenerate, and thus affect cranial esophageal function. Esophageal dysfunction is known to play a role in the development of aspiration pneumonia. If esophageal function could be determined at time of diagnosis of ILP, it may be possible to predict patients at higher risk of aspiration. Although most cases of ILP are considered (by definition) to be idiopathic, there are several reports of dogs experiencing concurrent generalized peripheral neuropathy.4,16,21 At admission, dogs are generally in respiratory distress and attention is focused on the upper airway. Without specific neurologic assessment, early neurologic dysfunction may be misinterpreted as weakness from hypoxia or orthopedic conditions, making it uncertain
whether the diagnosis is truly ‘‘idiopathic,’’ or in fact part of a more generalized peripheral neuropathy.21 Our objectives in this prospective, controlled, cohort study were: (1) to compare the incidence of esophageal dysfunction in dogs diagnosed with ILP to an age- and breed-matched control group of dogs; (2) to investigate if esophageal dysfunction in affected dogs was associated with development of aspiration pneumonia in the 1st postoperative year; and (3) to monitor postoperative neurologic status and clinical signs for 1 year. We adopted the null hypothesis that esophageal function would be similar in both cases and controls. Similarly, we hypothesized that esophageal function would not be associated with aspiration pneumonia in the case dogs and that neurologic status of cases would not change significantly over 1 year. MATERIALS AND METHODS Inclusion Criteria Dogs admitted (August 2005–November 2006) showing signs consistent with, and laryngoscopic evidence of, bilateral laryngeal paralysis were considered for inclusion into the case series. Dogs were excluded from consideration if the laryngeal paralysis was congenital, secondary to neoplasia or trauma, or if owners declined the study. The final diagnosis of bilateral ILP was made from laryngoscopic assessment of flaccid vocal folds and corniculate processes of the arytenoid cartilages, with failure to abduct in the presence of substantial respiratory excursions. Healthy, large breed dogs (430 kg), 46 years old, with no signs of respiratory or gastrointestinal disease were solicited for inclusion into the control series. Informed, signed owner consent was obtained for all dogs. Information obtained and diagnostic tests performed are provided (Table 1).
Esophageal Studies Dogs were not sedated for esophagrams and were positioned in right lateral recumbency. All procedures were performed or supervised by a board-certified radiologist (D.S.R.) and the study technician (M.C.F.), or principal investigator (B.J.S.). Esophagrams were recorded with 3 phases: (1) a liquid phase using a 10 mL aliquot of liquid barium sulfate suspension (Liquid E-Z-Paque; EZ-EM Inc., Lake Success, NY), administered orally50; (2) a canned phase using a 10 mL aliquot of 60% w/v barium sulfate mixed with 1 half cup of canned dog food administered orally; and (3) a kibble phase using 1 half cup of large kibble dog food coated with liquid barium sulfate administered orally. Oropharyngeal and esophageal function were observed under fluoroscopic guidance until the bolus reached the stomach. All studies were either recorded onto S-VHS video cassettes, or sent to the Picture Archiving and Communication System (PACS) in DICOM format (our institution was in the process of transitioning to a digital image storage server during the
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Table 1. Information Obtained from 32 Dogs with Idiopathic Laryngeal Paralysis (Cases) and 34 Healthy Age and Breed Matched Dogs (Controls) Cases
Date of admission or recheck History Weight Body condition score Emergency treatment details Physical examination Neurological examination Complete blood count Serum biochemistry Urinalysis Premium thyroid profilew antiAchR titerz Three view thoracic radiographs Lateral cervical radiograph Esophagram (3-phase) Preoperative laryngoscopy Postoperative laryngoscopy Postoperative clinical course Date of discharge
Controls
0 day
14 day
1 month
3 month
6 month
12 month
Yes Yes Yes Yes
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Yes Yes Yes
Yes Yes Yes
Yes Yes Yes
Yes Yes Yes
Yes Yes Yes
Yes
Yes
Yes
Yes Yes
Yes Yes
Yes
Yes
Yes
Yes
Yes
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Yes
Neurologic examination included assessment of gait, muscle tone, muscle atrophy, postural reactions, and patellar reflexes. Flexor-withdrawal reflexes were performed in both pelvic and thoracic limbs.51 wPremium thyroid profile: TT4, TT3, FT4, FT3, T4AA, T3AA, TGAA, TSH (thyroid data are not reported). zAcetylcholine receptor antibody titers
study). Upon study completion, all esophagramsswere digitized and computer randomized (Microsoft Excel Random Number Generation, Microsoft Corp., Seattle, WA) by nonstudy personnel, and interpreted by 3 independent, blinded reviewers. Two reviewers were board-certified radiologists (D.S.R., J.K.), and 1 review panel was a board-certified surgeon (B.J.S.) and a licensed veterinary technician (M.C.F.) together. Esophagrams were evaluated and graded (Table 2). Any gastroesophageal reflux not immediately cleared by a secondary wave was noted, as well as the presence of hiatal herniation.
Follow-Up Case dogs returned for rechecks at 14 days and 1, 3, 6, and 12 months. Owners were asked to observe their dog closely and were educated in detecting signs of aspiration pneumonia. At each recheck, a physical examination was performed, and the owner questioned on the following signs: stridor, exercise tolerance, coughing, throat-clearing, gagging, regurgitation, vomiting, inappetance, and lethargy. Lateral and ventrodorsal thoracic radiographs were performed at 1, 3, 6, and 12 months. Clinical neurologic examinations (Table 1) were performed consistently by the same clinician (B.J.S.) and repeated at the 6 and 12 month checks.51
Laryngoplasty Case dogs had left unilateral cricoarytenoid laryngoplasty performed, or supervised directly, by a board certified surgeon (B.J.S., J.G.H.). The cricothyroid joint was partially disarticulated just enough to facilitate exposure. The dorsal cricoarytenoideus muscle was transected and the cricoarytenoid joint disarticulated to partially expose the articular facets. The interarytenoid cartilage was not transected. Two 0 polypropylene sutures (26 mm half-circle needle, taper MO-6, Ethicon Inc., New Brunswick, NJ) were inserted from the caudodorsal aspect of the cricoid cartilage through the muscular process and articular facet of the left arytenoid cartilage. A snug fit was obtained, but care was taken not to overtighten the sutures. Laryngoscopic examination was performed after endotracheal extubation to confirm the adequate arytenoid cartilage abduction. Immediate postoperative clinical course and day of discharge were recorded.
Statistical Analysis Esophageal function for each phase was scored on an ordinal scale (0–4) by 3 independent observers (Table 2). Agreement between observers was evaluated by a Light’s weighted k statistic, for each phase. As a substantial k statistic (0.61 k 0.80) was obtained for each phase (liquid, 0.77; canned, 0.68; kibble, 0.73), observers’ scores were averaged to obtain a mean score of esophageal function, subsequently referred to as the mean esophageal score, with each of the 3 phases. As errors of the data were not normally distributed, mean esophageal scores between cases and controls were compared by the Wilcoxon rank sum test, and the data presented as median and interquartile range. To calculate if mean esophageal score was associated with the development of aspiration pneumonia, all cases were re-
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ESOPHAGEAL DYSFUNCTION IN DOGS WITH IDIOPATHIC LARYNGEAL PARALYSIS Table 2. Scoring Criteria for Esophagrams
Criteria for Scoring
Score
Bolus completely or almost cleared with primary contractile wave; completely cleared with secondary wave Bolus not cleared with primary contractile wave but cleared within 2 more waves Bolus persistently retained in cervical esophagus after 3 primary/ secondary waves Bolus persistently retained in cervical esophagus after 3 primary/ secondary waves and retrograde movement Lack of coordinated primary contractile wave with/without secondary wave. Laryngotracheal aspiration, nasopharyngeal reflux, failure to form a pharyngeal bolus, failure to transport the bolus into cranial esophagus
Table 3. Enrollment Information for 32 Dogs with Idiopathic Laryngeal Paralysis (ILP, Cases) and 34 Healthy Age and Breed Matched Dogs (Controls)
0 1
Number Enrolled Breeds represented
2 3
Cases (ILP)
Controls
32 22 Labrador Retrievers 3 mixed breed dogs 1 Golden Retriever 1 German Shepherd dog 1 Brittany Spaniel
34 22 Labrador Retrievers 8 mixed breed dogs 1 Golden Retriever 1 German Shepherd dog 1 English Springer spaniel 1 Basset Hound
4
stratified according to development of aspiration pneumonia or not and the mean esophageal scores of the liquid phase compared between the 2 strata using the Wilcoxon rank sum test. Data were reported as median (25th – 75th interquartile range). The frequency of neurologic signs in the cases at 0 and 12 months were compared by means of McNemar’s test. P-values were reported.
RESULTS Case Dogs (Table 3) The mean duration of clinical signs reported by owner was 9.7 months (range, 1–24 months) Signs included progressively worsening ‘‘labored breathing,’’ ‘‘heavier panting,’’ ‘‘honking breathing,’’ ‘‘shortness of breath,’’ ‘‘difficulty breathing,’’ and ‘‘roaring.’’ All owners reported exercise intolerance, and 7 (22%) dogs had collapsed previously in severe respiratory distress. One dog (3%) had a history of mycoplasma pneumonia (left cranial lung lobe), confirmed by bronchoalveolar lavage culture 1 month before admission for laryngeal paralysis. Eighteen dogs (56%) had a change in voice (described as a ‘‘raspy’’ or ‘‘hoarse’’ bark), and 10 owners (31%) stated there was no change in voice; 4 owners were unsure because their dogs rarely barked. There was little difference in mean duration of clinical signs between the 18 dogs with voice change (9.8 months) and the 10 without voice change (9.4 months). Twenty owners (62%) reported that their dog would cough or clear its throat and this was most often associated with eating or drinking, but occasionally occurred with exercise, or was unrelated to other events. Nine dogs (28%) had a history of regurgitation, gagging or ‘‘choking when eating or drinking.’’ Three dogs (9%) were admitted from the emergency service after emergency management and 1 of these dogs had a temporary tracheostomy tube. Eight dogs (25%) admitted as routine appointments decompensated during the consultation or shortly after, and required emergency care. Emergency management consisted of oxygen therapy,
Mean age (range) Gender Male:Female Mean weight Mean BCS (1–9)
2 Newfoundlands 1 Australian Shepherd dog 1 Hungarian Viszla 11.2 (7–15) 23:9 (2 intact F, 1 intact M) 36.1 kg 6
10.0 (6–16) 17:17 (1 intact F, 2 intact M) 33.3 kg 6
BCS, body condition score (9-point scale, with 1 ¼ emaciated and 9 ¼ morbidly obese)
0.5 mg or 1.0 mg acepromazine intravenously (IV), IV fluids, and cooling fan with 3 dogs being administered 0.25 mg/kg dexamethasone IV. Ice packs were placed in the axilla and groin if the dog remained persistently hyperthermic. The other 21 dogs were relatively stable, although 3 were administered 0.5 mg or 1.0 mg acepromazine IV because of excited behavior with stridorous breathing. Dogs that had been medicated had esophagraphy the next day. On physical examination, all dogs had stridorous breathing, 2 had cyanosis, and 1 had harsh lung sounds. Referred upper airway sounds were often auscultated over the thorax. Exercise tolerance was not tested. Other findings included single or multiple lipomata, nuclear sclerosis, thickened stifles with crepitus, pain on rising and/or hip extension, and excessive waxy debris in ears. Epulis, hypoplastic vulva and lick granuloma were unique findings in 3 dogs. Ten dogs (31%) had neurologic signs consisting of conscious proprioceptive deficits, mild ataxia and hindlimb weakness in 6, and moderate ataxia, muscle atrophy (hindlimb and temporal musculature particularly) and moderate paresis in 4.
Control Dogs (Table 3) No significant abnormalities referable to the respiratory or gastrointestinal systems were detected on physical examination. Other findings included nuclear sclerosis, thickened stifles, pain on hip and shoulder extension, sebaceous adenomata and lipomata. None of the control dogs had abnormal findings on clinical neurologic examination.
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Laboratory Findings Seventeen case dogs (53%) and 28 control dogs (82%) had normal hematologic profiles. Hematologic abnormalities included: mild mature neutrophilia, mild leucopenia, mildly abnormal platelet numbers and/or mild anemia, and were observed in both cases and controls. Serum biochemical profile results were considered normal in 12 cases (38%), and 19 controls (56%). The most common abnormal finding was a mild increase in liver enzyme concentrations (alanine aminotransferase, aspartate aminotranferase, serum alkaline phosphatase, and iditol dehydrogenase and/or cholesterol) which was found in 15 cases (47%) and 11 controls (32%). Slightly abnormal amylase, creatine kinase, glucose, total protein, and phosphorus concentrations, and occasional mild electrolyte derangements, and were seen in both cases and controls. Urinalysis results were largely unremarkable in both cases and controls. Two cases (6%) had evidence of urinary tract infection (which was subsequently confirmed on urine culture), and 3 cases (9%) had proteinuria. Two controls (6%) had proteinuria. Thyroid profiles were similar between cases and controls. Acetylcholine receptor antibody titers were o0.6 nm/L in all cases and controls. Diagnostic Imaging Findings Lateral Cervical Radiographs. Two case dogs did not have lateral cervical radiographs taken because of respiratory distress. Of 30 case dogs, no abnormalities were detected in 8 (27%), 21 (70%) had distended laryngeal ventricles, and 2 (7%) had calcified laryngeal cartilages. One case dog had distended ventricles and calcified cartilages. In 29 (85%) of 34 control dogs, no abnormalities were detected, 3 (9%) had mildly distended laryngeal ventricles, and 2 (6%) had calcified cartilages. Thoracic Radiographs. Using 3 view thoracic radiographs, 29 (90%) case dogs were considered to have a normal geriatric thorax, with a mild, diffuse bronchointerstitial lung pattern. Two dogs had changes in their lung fields: 1 (3%) had evidence of a resolving pneumonia in the left cranial lung lobe (consistent with previously diagnosed mycoplasma pneumonia) and 1 (3%) had a focal alveolar pattern with air bronchograms within its right middle lung lobe, consistent with (subclinical) aspiration pneumonia. Two case dogs had cardiomegaly, and 1 had a (subclinical) sliding hiatal hernia on 1 lateral projection. For control dogs, 33 (97%) were considered to have either a normal or changes consistent with a normal geriatric thorax and 1 (3%) dog had right-sided cardiomegaly. In both cases and controls, frequent extrathoracic abnormalities (eg, spondylosis, costochondral
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mineralization and ostephytes of the caudal humeral head) were seen. In 2 dogs (1 case, 1 control) a gastric foreign body was identified. Esophageal Fluoroscopy (Table 4). The kibble phase could not be evaluated in 4 case dogs; 2 were noncompliant, 1 because of aggression and 1 because of respiratory distress, and in 2 studies there were too few kibbles captured on the video to adequately evaluate the phase. One case dog aspirated during the liquid phase and the remaining phases were not performed. All controls successfully and enthusiastically completed all phases of the esophagram study. Mean esophageal scores in each phase were significantly higher in cases when compared with controls (Po.0001; Table 4). The 2 controls with mean esophageal scores 41 developed stridorous breathing and exercise intolerance consistent with laryngeal paralysis 5 and 6 months after their esophagram studies (C-05, C-31). Nearly all esophagrams were worse in liquid phase compared with canned and kibble: 22 (69%) case dogs had mean liquid esophageal scores 41, compared with 2 (6%) control dogs. Of the 10 case dogs that had liquid mean esophageal scores 1, 8 were Labrador Retrievers, 1 was a Hungarian Viszla, and 1 was a mixed breed. When esophageal dysfunction was present, all reviewers observed that the cervical and cranial thoracic esophagus, to the level of the heart base, was notably more affected than the remaining intrathoracic esophagus. Once the bolus had traversed the cranial thoracic esophagus, onward movement toward the stomach was generally rapid and without hesitation. Gastroesophageal reflux was noted in 20 (62%) case dogs and was considered severe in 3. Two (6%) control dogs had mild gastroesophageal reflux. Sliding hiatal herniation was observed in 4 (12%) case dogs and in none of the controls. Surgical Findings Induction of anesthesia for diagnosis of ILP in the 32 case dogs was achieved with propofol (6 mg/kg IV) in 26 dogs, sodium thiopental (20 mg/kg IV) in 5 dogs, and ketamine hydrochloride (10 mg/kg IV)/diazepam (0.5 mg/ kg IV) in 1 dog. Choice of induction agent was dependent on anesthesiologist or surgeon preference. All drugs were titrated to the minimum level that enabled laryngoscopy. Three dogs were also administered doxapram hydrochloride (0.5 or 1.0 mg/kg IV) to augment respiratory excursions. One dog did not have surgery but did have laryngeal examination to confirm diagnosis of ILP. All dogs had bilateral laryngeal paralysis. Mucosal erythema, edema, paradoxical movement, and right vocal cord fasciculations were commonly observed. Abduction of the left arytenoid cartilage and enlargement of the rima
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Table 4. Results of Esophagrams for Cases and Controls. Scores are the Mean of 3 Separate, Blinded Evaluations. Scores Range from 0 to 4 (See Table 2 for Description of Scoring Criteria) Mean Esophageal Scores: Cases Dog ID A-01 A-02 A-03 A-04 A-05 A-06 A-07 A-08 A-09 A-10 A-11 A-12 A-13 A-14 A-15 A-16 A-17 A-18 A-19 A-20 A-21 A-22 A-23 A-24 A-25 A-26 A-27 A-28 A-29 A-30 A-31 A-32
N
N N
AP AP N
AP
N
N N N, AP N, AP N
Median 25–75 IQR
Mean Esophageal Scores: Controls
Liquid
Can
Kibble
1.0 3.7 1.0 3.0 3.3 1.3 2.3 3.0 2.0 0.3 3.0 4.0 2.3 1.0 0.3 2.7 3.0 0.0 2.3 3.3 1.7 2.7 2.3 3.3 3.3 0.7 0.0 0.0 4.0 2.0 1.7 0.0
0.3 1.3 1.0 3.0 2.3 1.0 2.0 2.7 2.0 0.7 0.7 4.0 0.3 0.0 0.0 1.0 2.3 0.0 0.3 3.3 0.3 2.0 2.3 3.3 3.0 1.7 0.0 0.0 LTA 0.7 0.7 0.0
0.3 1.3 0.0 TFK 0.3 1.0 2.3 3.0 1.3 0.7 NC TFK 1.0 NC 0.0 1.0 1.3 0.0 0.3 2.7 0.3 2.0 2.3 2.0 2.3 1.3 0.0 0.0 LTA 1.7 1.0 0.0
2.3 1.0–3.0
1.0 0.3–2.3
1.0 0.3–2.0
Dog ID
Liquid
Can
Kibble
C-01 C-02 C-03 C-04 C-05 C-06 C-07 C-08 C-09 C-10 C-11 C-12 C-13 C-14 C-15 C-16 C-17 C-18 C-19 C-20 C-21 C-22 C-23 C-24 C-25 C-26 C-27 C-28 C-29 C-30 C-31 C-32 C-33 C-34 Median 25–75 IQR
0.0 0.0 0.7 0.0 3.0 0.0 0.0 0.0 0.3 1.0 1.0 0.0 0.0 0.0 0.0 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 2.0 0.0 0.0 0.0 0.0 0.0–0.0
0.0 0.0 0.0 0.0 0.7 0.0 0.7 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.3 0.0 0.0 0.0 0.0 0.0–0.0
0.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.0 0.0 0.0 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.7 0.0 0.0 0.0 0.0 0.0–0.0
AP, aspiration pneumonia within the study period; IQR, interquartile range; LTA, laryngotracheal aspiration; N, dogs with neurologic signs on enrollment; NC, noncompliant; TFK, too few kibbles in study to evaluate this phase.
glottidis was confirmed on postoperative laryngoscopic examination in the 31 dogs that had surgery. Postoperative recoveries were largely unremarkable and mean hospital stay was 2.8 nights (range, 1–8 nights). Follow-Up Findings Of the 32 case dogs, 2 were excluded from follow-up because they had surgery without supervision of the surgical authors and consistent technique could not be assured); 2 were lost to follow-up because of owner noncompliance; and 1 did not have surgery. Of the 27 dogs that had follow up, 22 (81%) had abnormal esophagrams and 7 (26%) had neurologic signs, as previously described, at enrollment.
14 Days. All 27 dogs had healed from surgery; 3 (11%) had developed seromas that subsequently resolved without intervention. All owners reported their dogs had improved breathing, but exercise tolerance was difficult to assess at this stage because of postoperative restriction of activity. Stridor had completely or almost completely resolved in 24 (89%) dogs, with 3 still moderately stridorous upon exercise or extreme excitement. This outcome remained consistent for the study duration. Fourteen (52%) dogs coughed, either occasionally or 3–4 times daily. Coughing was associated with eating and/or drinking in 9 (64%) and with exercise in 1 (7%) dog. Three (11%) dogs cleared their throats several times daily, 3 (11%) regurgitated water sometimes after drinking, and 5 (18%) had vomited during this early period. In 1 dog, vomiting was attributed to a
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food change, and in another, the dog had gorged in the toilet bowl and vomited twice. The other episodes of vomiting were single incidents that the owner could not relate to an inciting event. All dogs were eating well with good energy levels. 1 Month. Exercise tolerance was improved in all but 1 dog, which had concurrent neurologic and orthopedic problems limiting its activity. Thirteen (48%) dogs were coughing at this time : 9 associated with eating or drinking, and 4 coughing occasionally without any obvious association. Three (11%) dogs had regurgitated, and 1 (4%) had vomited. All dogs were eating well and had good energy levels. Thoracic radiographic findings were unchanged from previous studies apart from 1 (4%) dog that had evidence of resolving aspiration pneumonia. Four (15%) dogs had already had an episode of aspiration pneumonia (2 at 2 days, 1 at 14 days, and 1 at 15 days). 3 Months. Immediately before this recheck, 1 dog died after an apparent seizure. Exercise tolerance was improved in all but 1 dog and 13 (50%) of 26 dogs were coughing, 9 associated with eating or drinking and 4 coughing occasionally without any obvious association. Three (11%) dogs were occasionally gagging and regurgitating, and 3 (11%) cleared their throat several times daily. Five (19%) dogs had vomited. All dogs were eating well and had good energy levels. Thoracic radiographic findings were unchanged except for 1 (4%) dog where a patchy alveolar pattern in the caudal segment of the left cranial lung lobe was suggestive of an aspiration episode; however there were no associated clinical signs. Just after the 3 month recheck, 1 dog was euthanatized because of progressive generalized neuromuscular deterioration. 6 Months. Immediately before this recheck, 1 dog was euthanatized because of seizures. One (4%) dog was still coughing, but this was generally perceived by the owners to be less frequent, and usually associated with drinking or eating. Throat-clearing was evident in 4 (16%) dogs. Three (12%) dogs occasionally regurgitated after drinking large amounts of water, and 2 (8%) had vomited once. All dogs were eating well and were considered to have good energy levels for their age and neurologic status. All thoracic radiographic findings were considered normal except for 1 (4%) dog with evidence of resolving aspiration pneumonia (2nd episode at 4 months). Eight dogs that had been neurologically normal on enrollment had developed neurologic signs similar to those already seen, yielding 14 (58%) dogs with signs consistent with generalized neuromuscular disease at 6 months. One dog had vestibular signs. 12 Months. One (4%) dog had its 3rd episode of aspiration pneumonia and 1 (4%) was recovering from an episode of aspiration pneumonia that occurred 2 weeks before this recheck. There was no change in coughing,
throat-clearing, regurgitation or vomiting from the 6 month check. All 24 dogs had neurologic signs at this time compared with 6/24 (25%) at enrollment (Po.0001), and 14 (58%) at 6 months. Four (17%) dogs had slight ataxia and weakness, with conscious proprioceptive deficits; 9 (38%) had obvious ataxia, muscle atrophy and moderate weakness; and 10 (42%) had marked hind limb paresis. One dog (4%) was nonambulatory. Muscle atrophy appeared to be most prominent around epaxial, pelvic limb (especially semimembranosus and semitendinosus muscles) and temporal musculature. One dog had vestibular signs in addition to peripheral neuropathic signs. All dogs, except the dog with pneumonia, were eating well with good energy levels. Five (18.5%) of 27 dogs developed aspiration pneumonia during the study. The mean liquid esophageal scores in these 5 dogs (3.3; range, 2.3–4.0) were higher (P ¼ .02) than in the 22 dogs (1.5; range, 0.4–2.6) that did not develop aspiration pneumonia. One dog (A-12) had 3 episodes of aspiration pneumonia (2 days, 4 months, 12 months), and the other 4 dogs each had 1 episode (2 days, 14 days, 15 days, 11.5 months). All cases of aspiration pneumonia were detected early by owners and responded well to treatment.
DISCUSSION Represented breeds with acquired ILP in our study are consistent with other reports, with the Labrador Retriever predominating, a few mixed breeds, and occasional other breeds. Other features of ILP in our dogs including history, clinical signs, predominance of males, and geriatric onset also concur with previous reports.2,4,21–23,27,29 Our cases and controls were well matched for breed representation, weight, body condition score, laboratory findings, and radiographic findings. Control dogs were a mean of 14 months younger than case dogs and there were more female controls. In our opinion, the 2 cohorts were sufficiently similar to enable a credible comparison (Table 3). Dogs with ILP clearly have abnormal cervical and cranial thoracic esophageal motility compared with unaffected dogs in a similar breed and age distribution, and this is especially notable in the liquid phase. It appears that the larger, less compressible boluses of the canned and kibble phases stimulated the dysfunctional esophagus more effectively than the liquid bolus. Historical information is not adequate to predict esophageal dysfunction; most dogs with ILP had abnormal esophagrams, yet less than one-third of these dogs had a history of regurgitation or gagging. There are also limitations when asking owners to distinguish historically between true
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regurgitation (a sign of esophageal dysfunction) and vomiting. It was most interesting that the only 2 controls with mean esophageal scores 41 subsequently developed signs consistent with laryngeal paralysis. This suggests that esophageal dysfunction may occur early in the pathogenesis of this disease, and certainly earlier than clinical signs related to esophageal dysfunction, such as regurgitation. Three controls had a mean esophageal score of 1. Although a score of 1 was considered as abnormal in our study, it was commonly seen and may in fact be normal in elderly dogs. In humans, esophageal motility decreases with advanced age and this may also be true for geriatric dogs.52–54 Additionally, all dogs were positioned in lateral recumbency for the esophagrams, which may affect bolus transport through the esophagus.55 It would be ideal, and probably more comfortable for the dog, if the esophagrams could be performed in sternal or standing positions. The increased incidence of gastroesophageal reflux and hiatal herniation seen in case dogs compared with controls is consistent with a clinically dyspneic dog trying to generate greater subatmospheric pressures to move air past a paralyzed larynx. Although a decrease in esophageal motility can be associated with esophagitis because of gastroesophageal reflux,56 it is unlikely that the esophageal dysfunction we observed is because of gastroesophageal reflux or hiatal herniation. Esophageal dysfunction involved the cervical and cranial thoracic esophagus; the caudal thoracic esophagus was largely unaffected. Although the dogs with hiatal hernia were subclinical, we have seen dogs with hiatal herniation associated with laryngeal paralysis resolve after unilateral laryngoplasty. Review of veterinary anatomical and surgical publications highlights variable reporting of the nerve supply to the esophagus and larynx.1,44–46,49,51,57–59 Accurate anatomic and functional studies of esophageal and laryngeal innervation have been performed in the dog, and reveal the consistent presence of paired pRLNs supplying the cervical and cranial thoracic esophagus.49,60–62 The pRLNs branch from the RLNs close to their parent vagus nerves in the thorax. Specifically, the left RLN arises from the left vagus nerve near the arch of the aorta, immediately caudal to the origin of the left subclavian artery. It courses caudomedially across the ventral surface of the aorta, then curls medially around the dorsal aspect of the ligamentum arteriosum to run cranially. Just cranial to this point, the left pRLN originates, running dorsally, ascending over the cranial thoracic esophagus, supplying it with myriad branching and anastomosing branches, as it travels cranially, parallel and dorsal to the left RLN. The right RLN arises from the right vagus opposite the 1st rib, and curls around the right subclavian artery,
to lie on the trachea. Immediately after its origin, the right RLN divides into 2 parallel trunks: the right RLN ventrally, alongside the trachea, and the right pRLN dorsally. The right pRLN gives off many branches to the trachea and cervical esophagus along its course. Each pRLN continues cranially to anastomose with the internal branch of the cranial laryngeal nerve via the ramus anastomoticus, whereas each RLN terminates as the caudal laryngeal nerve to innervate the intrinsic muscles of the larynx.45,49 Watson described 3 regions of esophageal innervation in the dog: the cervical esophagus, innervated from the paired pharyngoesophageal and pRLNs; the cranial thoracic esophagus, mainly supplied by the left pRLN; and the caudal thoracic esophagus via the thoracic vagi and the vagal nerve trunks. It was postulated that the increased contribution from the left pRLN may be because the esophagus is predominantly a left sided structure at this level. The pattern of esophageal dysfunction we observed is strikingly consistent with the innervation from the pRLNs. Presumably, degeneration of the pRLN occurs concurrently with the deterioration occurring in the RLN. The somatic efferent fibers in the vagus nerve, from which the RLN and pRLN arise, have their cell bodies in the nucleus ambiguus, located in the medulla oblongata. These fibers supply the striated muscles of the pharynx, larynx, and esophagus, and are closely associated with the glossopharyngeal and particularly the accessory cranial nerves.31 It may be worthwhile imaging or obtaining necropsy samples of the nucleus ambiguus in future investigations of dogs with ILP. Dogs with higher mean esophageal scores were more likely to develop aspiration pneumonia. Esophageal dysfunction is well recognized as a risk factor for aspiration, and detection of megaesophagus postoperatively has been associated with a higher risk of complication and death in dogs with ILP.22,63 An esophagram is technically easy to perform and may be predictive for aspiration pneumonia. Our findings suggest that only the liquid phase need be performed. The esophagram appears to be more predictive of aspiration pneumonia than neurologic status, as only 2 of the 5 dogs that had aspiration pneumonia were neurologic at enrollment (Table 4). Aspiration pneumonia has been reported late in the postoperative period, sometimes after 1 year and indeed, we also observed this, with 2 dogs having episodes close to 1 year.22,27,40 It is possible that this may occur because of continued neurologic deterioration and progressive esophageal dysfunction, rather than because of an inability to adapt to the surgical procedure. Not only did 1/3 of dogs with ILP have neurologic signs at enrollment compared with none of the controls, but all dogs enrolled at study end had developed similar neurologic signs highly suggestive of generalized neuro-
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muscular disease. Although this finding is highly suggestive of a progressive neuropathy in dogs with ILP, one study limitation was that we did not reevaluate the neurologic status of the controls at 1 year. Neurologic abnormalities in geriatric dogs with laryngeal paralysis have been reported intermittently over the years, although comparison with an age and breed-matched control sample has not previously been performed.4,16,24 Recently, dogs with ILP have been shown to have electromyographic abnormalities and decreased motor nerve conduction velocities.21 There is other evidence suggestive that ILP is in fact a more generalized polyneuropathy. Early experimental studies showed that when both RLNs were sectioned, the glottis takes on a tightly adducted, rather than relaxed, appearance, because of the vocal cord tensor action of the unaffected cricothyroideus muscle (innervated via the cranial laryngeal nerve). It was extremely difficult to manually abduct the glottis, and these dogs were immediately severely dyspneic and had difficulty swallowing and vocalizing.62 This adducted position was markedly different from the relaxed, loose, paramedian positions we see in dogs with ILP. However, with bilateral sectioning of both the RLN and the external branch of the cranial laryngeal nerve (which supplies the cricothyroideus muscle), the glottis adopted the paramedian position observed in dogs with ILP, and the dogs had signs typical of laryngeal paralysis.62 From this perspective, it appears that dogs with ILP may also have concurrent cranial laryngeal nerve dysfunction, and that in fact denervation is more extensive than previously realized. The instrinsic branch of the cranial laryngeal nerve supplies sensation to the supraglottic laryngeal mucosa and innervates the taste buds on the epiglottis responsible for initiating the swallowing reflex. It has also been shown that afferent impulses from the cranial (superior) laryngeal nerve play a critical role in the initiation of pharyngeal swallowing in dogs.64 A more extensive neuropathy with decreased afferent impulses would also fit in with the throat-clearing and coughing behavior frequently seen in dogs with ILP. A limitation of our study is the lack of electromyographic examination and motor nerve conduction velocity testing. More than 1/3 (34%) of the dogs with ILP were either admitted as emergencies or became emergent after admission. With 1 in 4 dogs decompensating in the waiting or exam room, it is prudent to be prepared to institute emergency measures. Almost all dogs can be managed without any form of intubation. Even apparently stable dogs should be closely monitored in case of decompensation after admission. Many owners commented on how agitated the breathing in their dogs became upon entering our clinic. It appears that most dogs diagnosed with ILP are in fact presenting with chronic, progressive polyneuropathy,
and that until the disease is better understood, it may be better referred to as ‘‘geriatric onset laryngeal paralysis polyneuropathy’’ (GOLPP) syndrome. Electrodiagnostic testing on these dogs should be performed when available. We recommend performing liquid phase esophagrams on all dogs with laryngeal paralysis. Esophagrams should not be performed, however, when there is radiographic evidence of megaesophagus, or if the dog is in marked respiratory distress. If severe esophageal dysfunction is detected and surgical intervention is considered necessary to alleviate respiratory distress, an alternative technique could be considered.29,33–35,41 Clearly, our understanding of this form of geriatric onset laryngeal paralysis in dogs and our current means of addressing the compromised airway are less than ideal.65 Further studies are indicated to investigate the cause(s) and pathogenesis of this disease, as well as to refine techniques that restore a degree of function to the glottis, rather than simply increasing its cross-sectional area.
ACKNOWLEDGMENTS Study funded by the Michigan State University Companion Animal Fund. We thank Dr. Rob Malinowski, DVM, MA, Information Technology Group, College of Veterinary Medicine, Michigan State University, for digitizing, randomizing and blinding the esophagram studies.
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