Bacterial Meningitis After Sinus Surgery in Five Adult Horses Fabienne S. Bach1, Med. Vet., Gabor Bodo2, Dr. Med. Vet. PhD, Habil., Diplomate ECVS, Jan M. Kuemmerle1, Dr. Med. Vet., Diplomate ECVS, Astrid Bienert‐Zeit3, Dr. Med. Vet., Diplomate EVDC Eq, Edmund K. Hainisch4, Dr. Med. Vet., and Hubert Simhofer4, Dr. Med. Vet., Diplomate EVDC Eq 1 Equine Clinic, University of Zurich, Zurich, Switzerland ,2 Equine Clinic, Szent István University, Budapest, Hungary ,3 Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany and 4 Clinic for Large Animal Surgery, University for Veterinary Medicine, Vienna, Austria
Corresponding Author Fabienne S. Bach, Med. Vet., Equine Clinic, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, CH‐8057 Zurich, Switzerland. E‐mail: [email protected]. Submitted December 2012 Accepted December 2013 DOI:10.1111/j.1532-950X.2014.12132.x
Objective: To report meningoencephalitis as a complication after paranasal sinus surgery in 5 horses. Study Design: Case series. Animals: Adult horses (n ¼ 5). Methods: Medical records (2005–2010) of 5 horses that developed neurologic signs after sinus surgery were reviewed to identify potential risk factors, cause(s), or common pathways for infection. Results: Underlying diseases were primary (n ¼ 1) and secondary sinusitis (4) because of apical dental infection (1), sinus cyst (2), or masses in the ethmoturbinate region (2). Horses were treated by conventional surgical approaches and aftercare including repeated sinus lavage. Four horses had undulating pyrexia postoperatively despite antimicrobial therapy. All horses developed neurologic signs, eventually unresponsive to treatment. Suppurative meningoencephalitis was diagnosed macro‐ and/or microscopically on necropsy in all horses. Conclusion: Meningitis is a rare but fatal complication after sinus surgery in horses.
Despite improved outcomes with surgical management of diseases of the equine paranasal sinuses, complications occur.1 These include incisional drainage, sequestrum formation, periostitis, poor cosmetic outcomes, sinocutaneous fistulas, bone flap necrosis, excessive hemorrhage, complications associated with sinonasal packing, recurrence or incomplete resolution of disease processes, facial or nasal cavity deformities, infraorbital nerve trauma and its consequences.2 Extension of formalin into the cranial cavity resulting in brain damage after intralesional treatment of ethmoid hematoma has been reported.2,3 Apart from sporadic case reports there is little information about meningitis as complication of sinusitis or sinus surgery.4–6 Meningitis seems to be an uncommon complication of sinus surgery. Our purpose is to report meningoencephalitis as a complication of paranasal sinus surgery in 5 horses.
MATERIAL AND METHODS Inclusion Criteria Medical records (2005–2010) of 5 European clinics (Equine Veterinary Services “Shotter and Byers,” Cranleigh, UK; University of Veterinary Medicine Budapest, Hungary; Presented in part at the 10th International Association for Functional Improvement of Equine Dentition Congress, March 2012, Niedernhausen/Wiesbaden, Germany.
University of Veterinary Medicine Hannover, Germany; University of Veterinary Medicine Vienna, Austria; and Vetsuisse Faculty Zurich, Switzerland) were searched for horses that had paranasal sinus surgery, subsequently developed neurologic signs, and had a pathologic diagnosis of bacterial meningitis.
RESULTS Five horses (aged 3–23 years; 3 mares, 2 geldings; Table 1), that developed neurologic signs after paranasal sinus surgery were identified. There were 4 Warmbloods and 1 Polopony. Sinusitis was chronic (3–52 weeks duration) and associated with unilateral (n ¼ 4) or bilateral (1) purulent nasal discharge. Enlarged mandibular lymph nodes, facial swelling and epiphora were observed in 2 horses and the sinuses were dull on percussion in 4 horses. One horse was febrile (38.6°C) and 1 horse had cranial nerve deficits (reduced menace response and pupillary light reflex) on admission. None of the horses had hematologic abnormalities. All horses had mild abnormalities (sharp enamel points, focal dental overgrowths, mild mucosal lacerations) on oral examination. Food impaction of the caudal infundibulum of maxillary premolar Triadan 208 was identified in 1 horse and diastema formation between 109–110 and 209–210, respectively, were found in another horse. One horse had superficial buccal dental fractures on 110 and 210 that did not involve the pulp cavities. Horse 4 had fractures of 109 and 110 with pulp
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
697
698
Trephination CFS and CMS; frontonasal sinusotomy 52 Secondary sinusitis; soft tissue mass; paranasal sinus cyst 7 yr F Warmblood 5
Trephination CFS and CMS 8 23 yr G Warmblood 4
Secondary sinusitis; tooth root infection
10 yr F Warmblood 3
yr, year(s); F, female; G, gelding; CFS, conchofrontal sinus; CMS, caudal maxillary sinus; spp, species; ssp, subspecies; MRSA, methicillin resistant Staphylococcus aureus; ESBL, extended spectrum beta lactamase; E, Escherichia.
5 (7)
No sampling
Bach et al.
Oral dental extraction; ventral conchal bulla perforation; ventral nasal concha conchotomy Cyst and mass resection
11 (18)
Streptococcus equi ssp. zooepidemicus, Prevotella spp., Fusobacterium necrophorum, staphylococci MRSA, ESBL E. coli, Acinetobacter spp., Streptococcus equi ssp. zooepidemicus 13 24
22 yr G Polo Pony 2
Secondary sinusitis; bilateral paranasal sinus cyst Secondary sinusitis; rhinitis; soft tissue mass
20
Bilateral trephination CFS; unilateral trephination left CMS Frontonasal sinusotomy
Mass resection; partial conchectomy
No sampling 9 (11)
Streptococcus spp.; MRSA 12
Ventral conchal bulla perforation Bilateral sinus cyst resection Caudal maxillary sinusotomy 3 Primary sinusitis 3 yr F Warmblood 1
Surgical Approach Signalment
Diagnosis
Duration (Weeks) Horse
Table 1
Summary Data for 5 Horses That Developed Bacterial Meningitis After Sinus Surgery
Surgical Treatment
Days After Last (First) Surgery to Death
Bacteria Isolated
Bacterial Meningitis After Sinus Surgery
exposure; purulent discharge was present from a draining tract located on the buccal aspect of 109. Sinusitis was confirmed in all 5 horses by endoscopic evidence of purulent discharge from the nasomaxillary aperture. Nasal mucosal swelling was observed in all horses. Soft tissue masses in the middle nasal meatus and in the ethmoid area were noted in horses 3 and 5, but were not biopsied. In horse 3, the mass was a blackish color and located rostral to the left ethmoturbinate. The mass in horse 5 was blackish and extended from the left ethmoturbinate almost to the rostral end of the middle nasal meatus. Upon perforation of the mass mucopurulent fluid drained. Radiographic findings included increased unilateral soft tissue opacity of the caudal maxillary sinus (n ¼ 1) or increased unilateral (3) or bilateral (1) opacity of both the rostral and caudal maxillary sinuses with fluid accumulation.3 Clubbed tooth apices with periapical sclerosis of 109 and 110 were noted in horse 4; however, no dental abnormalities of the cheek teeth were evident in the other horses. Soft tissue opacities near the left ethmoturbinate consistent with the endoscopically detected masses were observed in horses 3 and 5. Horse 3 had CT; the rostral part of the left sphenopalatine sinus was filled with a homogenous mass of soft tissue density that extended rostrally in close contact with the left ethmoturbinate and left orbit. The surface of the left ethmoturbinate and bony structures adjacent to the left rhinencephalon appeared blurred. No signs of bony perforations were detected. The left conchofrontal and left caudal maxillary sinus were filled with fluid of moderate density. The mucous membranes of the left rostral maxillary sinus were markedly thickened and the left ventral conchal sinus seemed widened and contained homogenous material of soft tissue density. No related pathologic changes of the cheek teeth were observed. Based on these findings, primary (horse 1) or secondary sinusitis associated with apical dental infection (horse 4), bilateral paranasal sinus cysts (horse 2), rhinitis and a soft tissue mass in proximity to the ethmoturbinates (horse 3), and a unilateral paranasal sinus cyst as well as a soft tissue mass in proximity to the ethmoturbinates (horse 5) were diagnosed. Surgical management of sinusitis was attempted in all horses with 3 requiring >1 surgical intervention. Surgery was performed under general anesthesia (2), in the standing position (2 horses; 2–4 sessions), and in 1 horse under general anesthesia after an unsuccessful attempt with standing surgery. All horses were administered antibiotics perioperatively (amoxicillin/clavulanic acid [8.75 mg/kg intramuscularly {IM}] in horse 1; enrofloxacin [7 mg/kg intravenously {IV}] in horse 2; gentamicin (6.6 mg/kg IV), amoxicillin (20 mg/kg IM), and metronidazole (15 mg/kg orally) in horse 3; marbofloxacin [2 mg/kg IV; 1st and 2nd surgery] and enrofloxacin [7.5 mg/kg IV; 3rd and 4th surgery], respectively, in horse 4; trimethoprim/sulfamethoxazole [30 mg/kg orally; 1st surgery] and cefquinom [1mg/kg IV; 2nd surgery], respectively, in horse 5) and non‐steroidal anti‐inflammatory drugs (flunixin meglumine [1.1 mg/kg IV; horses 1, 3, 4]; phenylbutazone [2.2mg/kg orally; horses 2, 5]). The surgical field was aseptically prepared. Surgical approaches were unilateral (n ¼ 2) or bilateral (1) trephination of the
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
Bach et al.
conchofrontal sinus in 3 horses, trephination of the rostral/ caudal maxillary sinus (3), or use of frontonasal (2) or maxillary (1) bone flaps. Surgical procedures included penetration of the ventral conchal bulla (2), resection of sinus cysts (2) or soft tissue masses (2), conchotomy of the ventral nasal concha (1), and oral dental extraction (1; Table 1). Histopathology of the mass from horse 5 revealed a sinus cyst with proliferation of granulation tissue, purulent inflammation and a non‐neoplastic mucosal polyp with fresh hemorrhage and diffuse necrosis. The mass from horse 3 was characterized by severe chronic purulent inflammation, proliferation of connective tissue, and hemorrhage. Alterations typically associated with progressive ethmoid hematoma were not identified. The cause of the mass remained unclear. Intraoperative complications occurred in 3 horses1,2,4: severe hemorrhage occurred in 2 horses (2, 4); additionally, in horse 2, sinus irrigation was heavily impeded; in horse 1, increased irrigation pressure was required intraoperatively to irrigate the sinus system and during irrigation convulsions occurred. Pre‐ or intraoperatively collected samples for microbial culture (3) yielded growth of a mixed Streptococcus spp. from horse 1; Streptococcus equi ssp. zooepidemicus, Prevotella spp., Fusobacterium necrophorum and coagulase negative staphylococci from horse 3; and methicillin resistant Staphylococcus aureus (MRSA), extended‐spectrum b‐lactamase (ESBL) Escherichia coli, Acinetobacter sp., and Streptococcus equi ssp. zooepidemicus from horse 4. The initial microbial culture from this horse had no growth and the mixed culture was obtained 14 days later. Daily sinus lavage was performed in all horses with 0.5% povidone iodine diluted in isotonic saline (2), saline (1), or 0.05% chlorhexidine solution (2). Sinus irrigation was impeded postoperatively in 2 horses: horses 4 and 5 had insufficient drainage after the first surgery requiring further surgical interventions. Four horses were continuously administered systemic antibiotics after sinus surgery, whereas antibacterial therapy was discontinued after 4 days in horse 4 when multidrug resistant organisms were isolated on microbial culture. Postoperative antibiotic treatment included amoxicillin/ clavulanic acid (8.75 mg/kg IM twice daily; horse 1); enrofloxacin (7 mg/kg orally once daily and IV once daily, respectively, with onset of neurologic signs; horse 2); gentamicin (6.6 mg/kg IV once daily), amoxicillin (20 mg/kg IM twice daily), and metronidazole (15 mg/kg orally 3 times daily) for horse 3; enrofloxacin (7.5 mg/kg IV once daily; horse 4); cefquinom (1 mg/kg IV twice daily) and sodium penicillin (30,000 U/kg IV 4 times daily), and gentamicin (7 mg/kg IV once daily), respectively, with onset of neurologic signs for horse 5. All horses were administered non‐steroidal anti‐inflammatory drugs postoperatively: flunixin meglumine (1.1 mg/kg IV twice daily) in 2 horses and phenylbutazone (2.2 mg/kg orally twice daily) in 3 horses. None of the horses had signs of incisional infection. During treatment, 3 horses developed high undulating pyrexia (39.6–40.9°C); horse 4 had febrile peaks >40°C and
Bacterial Meningitis After Sinus Surgery
was also administered metamizole (40 mg/kg IV). Three horses had tachycardia and tachypnea. Within 5–11 days (mean SD; 8.8 2.3 days) after initial surgery and 4–11 (6.6 2.7) days after last surgery, respectively, all horses had signs of acute, progressive neurologic disease. The most common clinical signs were apathy and depression (n ¼ 5). Ataxia and general coordination deficits (3) and proprioceptive deficits (2) were observed. Other neurologic abnormalities included abnormal head and neck posture while lying in the stall (1), blindness (1), partial loss of head and body sensitivity (1), and collapse (1). One mare was circling, had compulsive walking and intermittent head pressing. All horses continued to deteriorate within a short period, leading to recumbency. At this stage, nystagmus and seizures occurred in horse 4. With onset of neurologic signs, phenylbutazone administration in 3 horses was discontinued and flunixin meglumine (1.1 mg/kg IV twice daily) administered. Prednisolone (1 mg/kg orally once daily) was administered to horse 3. With progressive deterioration, a single dosage of dexamethasone (0.08 mg/kg IV) was administered to horse 5. Terminal seizures in horse 4 were controlled with butorphanol and diazepam. Radiographs of the neck and head in horse 5 ruled out bone trauma; however, on upper respiratory tract endoscopy there was a large accumulation of necrotic tissue in the left maxillary and frontal sinus. Hematologic and serum biochemical findings had evidence of hemoconcentration (n ¼ 2), severe leukocytosis (4; 14.6–46.4 103/mL [reference interval; 5–10 103/mL]) and neutrophilia (4), hypoproteinemia (2), hyperfibrinogenemia (2), and hyperglycemia (2). Blood cultures were not performed in any horse. Cerebrospinal fluid was collected from all horses: 2 ante‐ mortem from the lumbosacral space and in 3 horses, from the atlanto‐occipital space at death. All CSF specimens had turbidity and xanthochromia, indicating inflammation of the central nervous system. Neutrophilic pleocytosis and markedly increased total protein concentration were diagnosed in 2 samples. Cytologic examination and microbial culture in 2 specimens yielded negative results. Necropsy Findings None of the horses had evidence of systemic infection; however, meningoencephalitis was evident in all horses. The predominant findings were turbid and discolored CSF and malacia of cerebrum in all horses and purulent and necrotizing inflammation of the pituitary gland in horses 1, 2, 4, and 5. In horse 3, the cribriform plate had necrotizing inflammation and the bone surface was irregular. Malacia was present in the rhinencephalon. The inner lining of the sphenopalatine sinus was inflamed, but bony structures seemed macroscopically intact. In all other horses, no signs of bone deformations or lesions were detected. Sinusitis was present in all horses, but individual compartments were not examined in detail. Meningitis and meningoencephalitis, respectively, were confirmed histologically in 3 horses where tissue samples were taken. Histopathologic examination of horse 4 revealed massive neutrophilic infiltration of intracranial vascular walls and adjacent tissues as well as intraluminal presence of
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
699
Bacterial Meningitis After Sinus Surgery
Bach et al.
bacteria. Bacterial culture of pia mater in 2 horses yielded massive growth of Streptococcus equi ssp. zooepidemicus (horse 4) and methicillin resistant S. aureus (MRSA) in horse 1. In horse 3, bacteria could not be detected (Ziehl‐Nielsen and Grocott staining) in brain tissue.
DISCUSSION Bacterial meningitis is associated with high mortality. There are only a few reports of successfully treated bacterial meningitis or intracranial abscesses in adult horses.7–10 Toth et al.11 reported 96% mortality in 28 horses with meningitis or meningoencephalomyelitis. In horses with a history of bacterial meningitis secondary to infectious disease processes of the head, 100% mortality occurred.4,5 None of our horses survived. The closed‐ space localization of infection and the proximity to central nervous control centers increase the risk of a fatal outcome.12 Size, weight, and behavior of affected horses also complicate intensive care, especially in recumbent horses.11 There are 4 likely main pathways for infection caused by disease processes of the head: via osteitis/erosion of thin bones4,5,13; vascular spread (hematogenous‐metastatic, thrombophlebotic)4,5,13,14; along cranial nerves4,13; or by direct bacterial inoculation caused by (iatrogenic) head trauma.8,10,11 Ostitis/Erosion Pathologic fractures of the cribriform plate of horses with severe frontal sinusitis have been reported.11,15 Infection of the cranial cavity is also facilitated if the integrity of the cribriform plate has been compromised by adjacent infection, neoplasia, tumor‐like lesions, or (iatrogenic) trauma.16,17 The sphenopalatine sinus is a further predilection site, because the wall adjacent the cranial cavity is extremely thin18 and is in close proximity to the cavernous sinus (Fig 1). Ostitis erosions may predispose to intracranial injury including meningitis and related disorders.18–22 McCann et al.18 suggest CT, MRI, and sinoscopy to improve detection of bony perforation; however, diagnosis is difficult even with radiography.20,23,24 Fractures of these bony structures were not identified on radiographic or CT examination at hospital admission in horse 3. Necropsy findings and diagnosis of a space‐occupying process adjacent the ethmoturbinates and in the sphenopalatine sinus, as well as blurred bony contours on CT examination, make transmission through the cribriform plate very likely in case 3. Yet, diagnostic imaging techniques, or microscopic examination for detection of microlesions, were not performed post mortem.
Figure 1 The lamina cribrosa of the ethmoid bone (red outline) and the dorsal wall of the sphenopalatine sinus (orange outline) are the predilection sites for ostitis erosion transmission. From: Popesko (2007)41, modified, with permission by Priroda publishing, Bratislava, Slovakia.
sinus system with the facial veins that lie beyond the cranium.25–27 In horses, the dorsal and ventral (basal) dural venous sinus systems are not directly connected. The ventral venous sinus system seems more important in the pathogenesis of ascending meningitis. The cavernous sinus is the central reservoir of the ventral sinus system and surrounds the pituitary gland. The cavernous sinus bilaterally anastomoses with the extracranial ophthalmic plexus via the orbital fissure emissary veins.26,27 The ophthalmic plexus merges into the deep facial vein, which collects the blood from parts of the facial and upper dental area,27 from the orbital and nasal cavity, and from the nasal conchae.26 Because of the venous characteristics, spread of infection from the dentofacial area into the dural venous sinus system is possible25 either in a hematogenous‐metastatic or phlebitic manner14 (Fig 2). Given that purulent and necrotizing inflammation of the pituitary gland and intracranial phlebitis/bacteremia (horse 4) were identified but bony structures of the cranial vault, especially of the sphenopalatine sinus and cribriform plate, seemed macroscopically intact in horses 1, 2, 4, and 5, this hematogenous route of infection seems most likely for these cases; however, combinations of pathways are possible. Detailed morphologic examination of vessels and vascular relationships could substantiate thrombophlebitic spread of infection, as reported by Smith et al.4 Cranial Nerves
Vascular/Hematogenous Infection The intracranial venous system has characteristic anatomic features. The veins are not accompanied by arteries and open into dural venous sinuses. Both veins and dural venous sinuses lack a smooth muscle layer and valves, thus vasoconstriction is impeded and bidirectional blood flow is possible depending on vascular pressures. Emissary veins connect the intracranial
700
In ruminants, encephalitic listeriosis appears to result from migration of bacteria along the trigeminal nerve to the brainstem. Bacteria have been observed within neurons and axons and a mechanism for cell‐to‐cell spread has been postulated.28 Smith et al.4 hypothesized the possibility of ascending infections along the olfactory and optic nerve in horses based on finding infection and bacteria in close
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
Bach et al.
Bacterial Meningitis After Sinus Surgery
Figure 2 Schematic illustration of the vascular pathway of infection: the deep facial vein collects the venous blood from the dentofacial area (respective drainage areas in italic) and is connected to the cavernous sinus, which surrounds the pituitary gland. Because of venous characteristics, transmission of infection into the cranial vault is possible.
proximity to the cribriform plate, in the periorbital region, and the optic chiasm. Although findings of purulent infection on both sides of the cribriform plate and fungal elements along olfactory nerves indicate the possibility of ascending infection by this route, clear evidence of neuritis or continuous bacterial invasion of nerve tracts over their entire length was not documented. This was also true for the suggested correlation between bacteria in the periorbital tissues and microscopic abscesses in the optic chiasm, which could alternatively have been transmitted by previously affected meninges or the pituitary gland, which lie in close proximity. Furthermore, a combination of spread of infection along olfactory fibers and through a compromised cribriform plate seems more likely than an exclusively nerve associated transmission. Visual disturbances in horse 3 are most likely explained by the history of facial swelling, chronic sinusitis, and diagnosis of a space‐occupying mass. Chronic sphenopalatine sinusitis29 and different types of nasal and paranasal sinus tumors17 can affect the optic nerve. Ascending nerve infection cannot completely be ruled out, because morphologic examination of the optic nerve and the optic chiasm was not conducted. Head Trauma Traumatic injury to the skull with secondary meningitis or intracranial abscess8,10,11 and iatrogenic damage to the cranial
vault during surgical excision of dentigerous cysts has been reported.30–32 Surgical excision of tumors or tumor‐like lesions could result in similar complications. None of our horses had signs of head trauma ante‐ or postmortem. The question arises, whether the surgical procedures performed were the cause of, or at least triggered, meningitis in our horses or whether this complication of sinusitis would have occurred anyway. General predispositions for meningitis include immunocompromised states33 or septicemia,12 which may play a role in foals and in adult horses.13,34–36 There was no clinical or other evidence of immunodeficiency in our horses; however, specific testing was not performed. Horse 5 had transient pyrexia on admission but this resolved before surgery, although the possibility of this being associated with subsequent infection cannot be excluded. Most sinus surgery is not clean2 and all of our horses had at least 1 invasive surgical procedure resulting in considerable surgical trauma. Presence of necrotic tissue, inspissated pus and clotted blood are an ideal environment for bacterial growth. Although none of the horses had signs of superficial surgical site infection,37 the contaminated intrasinus environment may have contributed to development of meningitis. Waguespack et al.37 mention local necrosis and release of proteolytic enzymes as a mechanism for facilitating expansion into adjacent regions. Endotoxins and peptidases from injured tissues can activate vasoactive peptides, the clotting and
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
701
Bacterial Meningitis After Sinus Surgery
Bach et al.
fibrinolytic cascades, and alter systemic resistance. This seems especially interesting in the light of possible bacteremic/ phlebitic spread of infection. The relationship between intraoperative incidents and meningitis is unknown in our horses. Substantial hemorrhage (horses 2, 4) has been described as a major risk of sinus surgery2,6 leading to reduced visibility in the surgical field,6 to systemic disturbances, and a potential loss of immunoresistance.37 Hemorrhage increases the risk of incomplete tissue removal and inadvertent lacerations of delicate structures (e.g., cribriform plate, nerves). It is conspicuous that drainage was inadequate in 4 horses (1 and 2 [intraoperatively], 4 and 5 [postoperatively]). Blood clots, soft tissue swellings, and incompletely resected masses or cysts represent obstacles which can impede irrigation, resulting in increased pressure in the sinonasal system during flushing, such that devitalized tissues and delicate structures could be injured and bacterial invasion facilitated. Accumulation of infectious material because of insufficient drainage provides continuing nidus for infection. We are unaware of any study describing the effect of sinonasal irrigation on intracranial pressure. Head positioning affects intracranial pressure,38 and seizures in horses can result from increased intracranial pressure.12 Positioning with lowered head during general anesthesia in conjunction with high pressure flushing of the sinonasal system could have markedly increased intracranial pressure, leading to convulsions in horse 1. In horse 4, Streptococcus equi ssp. zooepidemicus isolated at necropsy is recognized as a meningitis causing pathogen in adult horses.13 In a previous sample from the sinuses of this horse, MRSA and ESBL E. coli were isolated and antibiotic therapy was discontinued. There is ample room for speculation as to whether continued antibiotic therapy may have saved this horse as no multidrug resistant organisms were found intracranially. The other 4 horses received antibiotics continuously, yet in 2 horses (2, 5) susceptibility testing was not performed. Interestingly, the initial culture from the sinuses of horse 1 yielded growth of Streptococcus ssp., whereas MRSA was isolated from the meninges at necropsy. Whether MRSA infection was present at the surgical site at the onset of meningitis is unknown. The mixed isolates from our cases appear to preclude a common virulent strain of bacterium, although some horses were eventually unresponsive to treatment. There are some empirical reports of successful antibiotic protocols in equine meningitis,4,10,39 and recommendations for appropriate treatment of bacterial meningitis are reported.9,12,13 Complications associated with human endoscopic endonasal sinus surgery have become rare.40 Although outcomes from human sinonasal surgery are difficult to compare with outcomes in horses, use of preoperative diagnostic imaging (CT, MRI) and increased use of minimally invasive surgical methods (e.g., transnasal sinoscopy; personal communication, Simhofer H, October 2012) might further reduce postoperative complications in horses. Meningitis is an uncommon but mostly fatal complication that can occur after sinus surgery in horses. The contributing cause(s) of meningitis in these horses is speculative and the small number of cases within this series makes it difficult to
702
draw conclusions concerning preventative measurements. However, risk factors likely include a combination of surgically traumatized tissue, compromised drainage, high irrigation pressures, anatomic proximity to the cranial vault and nerves, and the presence of multidrug resistant organisms. As soon as suspicious clinical signs such as hyperthermia, depression, or neurologic signs are encountered, a detailed neurologic evaluation including hematology, CSF analysis, microbial sampling, and sensitivity testing and exclusion of differential diagnoses is warranted, followed by appropriate aggressive therapy as indicated.
REFERENCES 1. Dixon PM, Parkin TD, Collins N, et al: Equine paranasal sinus disease: a long‐term study of 200 cases (1997–2009): treatments and long‐term results of treatments. Equine Vet J 2012;44:272– 276 2. Ahern BJ, Parente EJ: Surgical complications of equine upper respiratory tract. Vet Clin Equine 2009;24:465–484 3. Frees KE, Gaughan EM, Lillich JD, et al: Severe complication after administration of formalin for treatment of progressive ethmoidal hematoma in a horse. J Am Vet Med Assoc 2001;219:950–952 4. Smith JJ, Provost PJ, Paradis MR: Bacterial meningitis and brain abscesses secondary to infectious disease processes involving the head in horses: seven cases (1980–2001). J Am Vet Med Assoc 2004;224:739–742 5. Reilly L, Habecker P, Beech J, et al: Pituitary abscesses and basilar empyema in 4 horses. Equine Vet J 1994;26:424–426 6. Hart SK, Sullins KE: Evaluation of a novel post‐operative treatment for sinonasal disease in the horse (1996–2007). Equine Vet J 2011;43:24–29 7. Atherton RP, Mitchell EV, McKenzie HC, et al: Traumatic fracture of the basisphenoid and secondary bacterial meningitis in a Thoroughbred gelding. Equine Vet Educ 2007;19:359–364 8. Cornelisse CJ, Schott HC II, Lowrie CT, et al: Successful treatment of intracranial abscesses in 2 horses. J Vet Intern Med 2001;15:494–500 9. Mitchell E, Furr MO, McKenzie HC: Antimicrobial therapy for bacterial meningitis. Equine Vet Educ 2007;19:316–323 10. Newton SA: Suspected bacterial meningoencephalitis in two adult horses. Vet Rec 1998;142:665–669 11. Toth B, Aleman M, Nogradi N, et al: Meningitis and meningoencephalomyelitis in horses: 28 cases (1985–2010). J Am Vet Med Assoc 2012;240:580–587 12. Pellegrini‐Masini A, Livesey LC: Meningitis and encephalomyelitis in horses. Vet Clin Equine 2006;22:553– 589 13. Furr M: Bacterial infections of the central nervous system, in Furr M, Reed S (eds): Equine neurology. Ames, IA, Blackwell Publishing, 2008, pp 187–212 14. Lehnerdt G, Peraud A, Berghaus A, et al: Orbitale und intrakranielle Komplikationen akuter Sinusitiden. HNO 2010;59:75–88 15. Freeman DE: Sinus disease. Vet Clin Equine 2003;19:209–243
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
Bach et al.
Bacterial Meningitis After Sinus Surgery
16. Zaruby JF, Livesey MA, Percy DH: Ethmoid adenocarcinoma perforating the cribriform plate in the horse. Cornell Vet 1993;83:283–289
29. Barnett KC, Blunden AS, Dyson SJ, et al: Blindness, optic atrophy and sinusitis in the horse. Vet Ophthalmol 2008;11 (Suppl1):20–26
17. Head KW, Dixon PM: Equine nasal and paranasal sinus tumours. Part 1: review of the literature and tumor classification. Vet J 1999;157:261–278
30. Barakzai SZ, Dixon PM: Dentigerous cysts. Equine Vet Educ 2012;24:579–581
18. McCann JL, Dixon PM, Mayhew IG: Clinical anatomy of the equine sphenopalatine sinus. Equine Vet J 2004;36:466–472
31. Hunt RJ, Allen D, Mueller E: Intracranial trauma associated with extraction of a temporal ear tooth (dentigerous cyst) in a horse. Cornell Vet 1991;81:103–108
19. Riegg A: Squamous cell carcinoma involving the facial sinuses and air passages in a horse (clinical reports). Vet Med 1946;41:142–143
32. Cronau M, Gerhards H: Matiasek, K: Multiple dentigerous cysts in a 6‐year‐old chestnut warmblood gelding. A case report. Tierarztl Prax Grosstiere Nutztiere 2009;2:129–133
20. Behrens E, Schumaker J, Morris E: Contrast paranasal sinusograpy for evaluation of disease of the paranasal sinuses of five horses. Vet Radiol 1991;32:105–109
33. Brouwer MC, Tunkel AR, van de Beek D: Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010;23:467–492
21. Tremaine WH: A clinical and histopathological study of the equine upper respiratory tract disease. M. Phil. Thesis, University of Edinburgh, 1997
34. Pellegrini‐Masini A, Bentz AI, Johns IC, et al: Common variable immunodeficiency in three horses with presumptive bacterial meningitis. J Am Vet Med Assoc 2005;227:114–122
22. Dixon PM, Head KW: Equine nasal and paranasal sinus tumours: part 2: a contribution of 28 case reports. Vet J 1999;157:279–294
35. Clark EG, Turner AS, Boysen BG, et al: Listeriosis in an Arabian foal with combined immunodeficiency. J Am Vet Med Assoc 1978;172:363–366
23. Gerber H: Nasennebenhoehlen, in Wintzer HJ, (ed): Krankheiten des Pferdes: Ein Leitfaden fuer Studium und Praxis (ed 3). Berlin, Parey, 1999, pp 7–11 24. Taylor DS, Wisner ER, Kuesis BS, et al: Gas accumulation in the subarachnoid space resulting from blunt trauma to the occipital region of a horse. Vet Radiol Ultrasound 1993;34:191–193 25. Stoffel MH: Funktionelle Neuroanatomie für die Tiermedizin. Stuttgart, Enke, 2011, pp 117–120
36. Flaminio MJBF, Tallmadge RL, Salles‐Gomes COM, et al: Common variable immunodeficiency in horses is characterized by B cell depletion in primary and secondary lymphoid tissues. J Clin Immun 2009;29:107–116 37. Waguespack RW, Burba DJ, Moore RM: Surgical site infection and the use of antimicrobials, in Auer JA, Stick JA (eds): Equine surgery (ed 3). Philadelphia, PA, Saunders, 2006, pp 70–87
26. König HE, Liebich HG, Cerveny C: Nervensystem (systema nervorum), in König HE, Liebich HG (eds): Anatomie der Haussäugetiere: Lehrbuch und Farbatlas für Studium und Praxis, Bd II (Organe, Kreislauf‐ und Nervensystem. Stuttgart, Schattauer, 1999, pp 203–276
38. Moore RM, Trim CM: Effect of hypercapnia or xylacine on lateral ventricle and lumbosacral cerebrospinal fluid pressures in pentobarbital‐anesthetized horses. Vet Surg 1993;22:151–158
27. Seiferle E: Gefäßversorgung von Rückenmark und Gehirn, in Nickel R, Schummer A, Seiferle E (eds): Lehrbuch der Anatomie der Haustiere (ed 4). Stuttgart, Parey, 2004, pp 209–227
40. Siedek V, Pilzweger E, Betz C, et al: Complications in endonasal sinus surgery: a 5‐year retrospective study of 2596 patients. Eur Arch Otorhinolaryngol 2013;270:141–148
28. Morin DE: Brainstem and cranial nerve abnormalities: listeriosis, otitis media/interna and pituitary abscess syndrome. Vet Clin Food Anim 2004;20:243–273
41. Popesko P: Median section through cranial cavity, in Popesko P (ed): Atlas of topographical anatomy of domestic animals (ed 6). Stuttgart, Enke, 2007, p 138
39. Mitchell E, Furr MO, McKenzie HC: Bacterial meningitis in five mature horses. Equine Vet Educ 2006;18:249–255
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
703
Corresponding Author Fabienne S. Bach, Med. Vet., Equine Clinic, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, CH‐8057 Zurich, Switzerland. E‐mail: [email protected]. Submitted December 2012 Accepted December 2013 DOI:10.1111/j.1532-950X.2014.12132.x
Objective: To report meningoencephalitis as a complication after paranasal sinus surgery in 5 horses. Study Design: Case series. Animals: Adult horses (n ¼ 5). Methods: Medical records (2005–2010) of 5 horses that developed neurologic signs after sinus surgery were reviewed to identify potential risk factors, cause(s), or common pathways for infection. Results: Underlying diseases were primary (n ¼ 1) and secondary sinusitis (4) because of apical dental infection (1), sinus cyst (2), or masses in the ethmoturbinate region (2). Horses were treated by conventional surgical approaches and aftercare including repeated sinus lavage. Four horses had undulating pyrexia postoperatively despite antimicrobial therapy. All horses developed neurologic signs, eventually unresponsive to treatment. Suppurative meningoencephalitis was diagnosed macro‐ and/or microscopically on necropsy in all horses. Conclusion: Meningitis is a rare but fatal complication after sinus surgery in horses.
Despite improved outcomes with surgical management of diseases of the equine paranasal sinuses, complications occur.1 These include incisional drainage, sequestrum formation, periostitis, poor cosmetic outcomes, sinocutaneous fistulas, bone flap necrosis, excessive hemorrhage, complications associated with sinonasal packing, recurrence or incomplete resolution of disease processes, facial or nasal cavity deformities, infraorbital nerve trauma and its consequences.2 Extension of formalin into the cranial cavity resulting in brain damage after intralesional treatment of ethmoid hematoma has been reported.2,3 Apart from sporadic case reports there is little information about meningitis as complication of sinusitis or sinus surgery.4–6 Meningitis seems to be an uncommon complication of sinus surgery. Our purpose is to report meningoencephalitis as a complication of paranasal sinus surgery in 5 horses.
MATERIAL AND METHODS Inclusion Criteria Medical records (2005–2010) of 5 European clinics (Equine Veterinary Services “Shotter and Byers,” Cranleigh, UK; University of Veterinary Medicine Budapest, Hungary; Presented in part at the 10th International Association for Functional Improvement of Equine Dentition Congress, March 2012, Niedernhausen/Wiesbaden, Germany.
University of Veterinary Medicine Hannover, Germany; University of Veterinary Medicine Vienna, Austria; and Vetsuisse Faculty Zurich, Switzerland) were searched for horses that had paranasal sinus surgery, subsequently developed neurologic signs, and had a pathologic diagnosis of bacterial meningitis.
RESULTS Five horses (aged 3–23 years; 3 mares, 2 geldings; Table 1), that developed neurologic signs after paranasal sinus surgery were identified. There were 4 Warmbloods and 1 Polopony. Sinusitis was chronic (3–52 weeks duration) and associated with unilateral (n ¼ 4) or bilateral (1) purulent nasal discharge. Enlarged mandibular lymph nodes, facial swelling and epiphora were observed in 2 horses and the sinuses were dull on percussion in 4 horses. One horse was febrile (38.6°C) and 1 horse had cranial nerve deficits (reduced menace response and pupillary light reflex) on admission. None of the horses had hematologic abnormalities. All horses had mild abnormalities (sharp enamel points, focal dental overgrowths, mild mucosal lacerations) on oral examination. Food impaction of the caudal infundibulum of maxillary premolar Triadan 208 was identified in 1 horse and diastema formation between 109–110 and 209–210, respectively, were found in another horse. One horse had superficial buccal dental fractures on 110 and 210 that did not involve the pulp cavities. Horse 4 had fractures of 109 and 110 with pulp
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
697
698
Trephination CFS and CMS; frontonasal sinusotomy 52 Secondary sinusitis; soft tissue mass; paranasal sinus cyst 7 yr F Warmblood 5
Trephination CFS and CMS 8 23 yr G Warmblood 4
Secondary sinusitis; tooth root infection
10 yr F Warmblood 3
yr, year(s); F, female; G, gelding; CFS, conchofrontal sinus; CMS, caudal maxillary sinus; spp, species; ssp, subspecies; MRSA, methicillin resistant Staphylococcus aureus; ESBL, extended spectrum beta lactamase; E, Escherichia.
5 (7)
No sampling
Bach et al.
Oral dental extraction; ventral conchal bulla perforation; ventral nasal concha conchotomy Cyst and mass resection
11 (18)
Streptococcus equi ssp. zooepidemicus, Prevotella spp., Fusobacterium necrophorum, staphylococci MRSA, ESBL E. coli, Acinetobacter spp., Streptococcus equi ssp. zooepidemicus 13 24
22 yr G Polo Pony 2
Secondary sinusitis; bilateral paranasal sinus cyst Secondary sinusitis; rhinitis; soft tissue mass
20
Bilateral trephination CFS; unilateral trephination left CMS Frontonasal sinusotomy
Mass resection; partial conchectomy
No sampling 9 (11)
Streptococcus spp.; MRSA 12
Ventral conchal bulla perforation Bilateral sinus cyst resection Caudal maxillary sinusotomy 3 Primary sinusitis 3 yr F Warmblood 1
Surgical Approach Signalment
Diagnosis
Duration (Weeks) Horse
Table 1
Summary Data for 5 Horses That Developed Bacterial Meningitis After Sinus Surgery
Surgical Treatment
Days After Last (First) Surgery to Death
Bacteria Isolated
Bacterial Meningitis After Sinus Surgery
exposure; purulent discharge was present from a draining tract located on the buccal aspect of 109. Sinusitis was confirmed in all 5 horses by endoscopic evidence of purulent discharge from the nasomaxillary aperture. Nasal mucosal swelling was observed in all horses. Soft tissue masses in the middle nasal meatus and in the ethmoid area were noted in horses 3 and 5, but were not biopsied. In horse 3, the mass was a blackish color and located rostral to the left ethmoturbinate. The mass in horse 5 was blackish and extended from the left ethmoturbinate almost to the rostral end of the middle nasal meatus. Upon perforation of the mass mucopurulent fluid drained. Radiographic findings included increased unilateral soft tissue opacity of the caudal maxillary sinus (n ¼ 1) or increased unilateral (3) or bilateral (1) opacity of both the rostral and caudal maxillary sinuses with fluid accumulation.3 Clubbed tooth apices with periapical sclerosis of 109 and 110 were noted in horse 4; however, no dental abnormalities of the cheek teeth were evident in the other horses. Soft tissue opacities near the left ethmoturbinate consistent with the endoscopically detected masses were observed in horses 3 and 5. Horse 3 had CT; the rostral part of the left sphenopalatine sinus was filled with a homogenous mass of soft tissue density that extended rostrally in close contact with the left ethmoturbinate and left orbit. The surface of the left ethmoturbinate and bony structures adjacent to the left rhinencephalon appeared blurred. No signs of bony perforations were detected. The left conchofrontal and left caudal maxillary sinus were filled with fluid of moderate density. The mucous membranes of the left rostral maxillary sinus were markedly thickened and the left ventral conchal sinus seemed widened and contained homogenous material of soft tissue density. No related pathologic changes of the cheek teeth were observed. Based on these findings, primary (horse 1) or secondary sinusitis associated with apical dental infection (horse 4), bilateral paranasal sinus cysts (horse 2), rhinitis and a soft tissue mass in proximity to the ethmoturbinates (horse 3), and a unilateral paranasal sinus cyst as well as a soft tissue mass in proximity to the ethmoturbinates (horse 5) were diagnosed. Surgical management of sinusitis was attempted in all horses with 3 requiring >1 surgical intervention. Surgery was performed under general anesthesia (2), in the standing position (2 horses; 2–4 sessions), and in 1 horse under general anesthesia after an unsuccessful attempt with standing surgery. All horses were administered antibiotics perioperatively (amoxicillin/clavulanic acid [8.75 mg/kg intramuscularly {IM}] in horse 1; enrofloxacin [7 mg/kg intravenously {IV}] in horse 2; gentamicin (6.6 mg/kg IV), amoxicillin (20 mg/kg IM), and metronidazole (15 mg/kg orally) in horse 3; marbofloxacin [2 mg/kg IV; 1st and 2nd surgery] and enrofloxacin [7.5 mg/kg IV; 3rd and 4th surgery], respectively, in horse 4; trimethoprim/sulfamethoxazole [30 mg/kg orally; 1st surgery] and cefquinom [1mg/kg IV; 2nd surgery], respectively, in horse 5) and non‐steroidal anti‐inflammatory drugs (flunixin meglumine [1.1 mg/kg IV; horses 1, 3, 4]; phenylbutazone [2.2mg/kg orally; horses 2, 5]). The surgical field was aseptically prepared. Surgical approaches were unilateral (n ¼ 2) or bilateral (1) trephination of the
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
Bach et al.
conchofrontal sinus in 3 horses, trephination of the rostral/ caudal maxillary sinus (3), or use of frontonasal (2) or maxillary (1) bone flaps. Surgical procedures included penetration of the ventral conchal bulla (2), resection of sinus cysts (2) or soft tissue masses (2), conchotomy of the ventral nasal concha (1), and oral dental extraction (1; Table 1). Histopathology of the mass from horse 5 revealed a sinus cyst with proliferation of granulation tissue, purulent inflammation and a non‐neoplastic mucosal polyp with fresh hemorrhage and diffuse necrosis. The mass from horse 3 was characterized by severe chronic purulent inflammation, proliferation of connective tissue, and hemorrhage. Alterations typically associated with progressive ethmoid hematoma were not identified. The cause of the mass remained unclear. Intraoperative complications occurred in 3 horses1,2,4: severe hemorrhage occurred in 2 horses (2, 4); additionally, in horse 2, sinus irrigation was heavily impeded; in horse 1, increased irrigation pressure was required intraoperatively to irrigate the sinus system and during irrigation convulsions occurred. Pre‐ or intraoperatively collected samples for microbial culture (3) yielded growth of a mixed Streptococcus spp. from horse 1; Streptococcus equi ssp. zooepidemicus, Prevotella spp., Fusobacterium necrophorum and coagulase negative staphylococci from horse 3; and methicillin resistant Staphylococcus aureus (MRSA), extended‐spectrum b‐lactamase (ESBL) Escherichia coli, Acinetobacter sp., and Streptococcus equi ssp. zooepidemicus from horse 4. The initial microbial culture from this horse had no growth and the mixed culture was obtained 14 days later. Daily sinus lavage was performed in all horses with 0.5% povidone iodine diluted in isotonic saline (2), saline (1), or 0.05% chlorhexidine solution (2). Sinus irrigation was impeded postoperatively in 2 horses: horses 4 and 5 had insufficient drainage after the first surgery requiring further surgical interventions. Four horses were continuously administered systemic antibiotics after sinus surgery, whereas antibacterial therapy was discontinued after 4 days in horse 4 when multidrug resistant organisms were isolated on microbial culture. Postoperative antibiotic treatment included amoxicillin/ clavulanic acid (8.75 mg/kg IM twice daily; horse 1); enrofloxacin (7 mg/kg orally once daily and IV once daily, respectively, with onset of neurologic signs; horse 2); gentamicin (6.6 mg/kg IV once daily), amoxicillin (20 mg/kg IM twice daily), and metronidazole (15 mg/kg orally 3 times daily) for horse 3; enrofloxacin (7.5 mg/kg IV once daily; horse 4); cefquinom (1 mg/kg IV twice daily) and sodium penicillin (30,000 U/kg IV 4 times daily), and gentamicin (7 mg/kg IV once daily), respectively, with onset of neurologic signs for horse 5. All horses were administered non‐steroidal anti‐inflammatory drugs postoperatively: flunixin meglumine (1.1 mg/kg IV twice daily) in 2 horses and phenylbutazone (2.2 mg/kg orally twice daily) in 3 horses. None of the horses had signs of incisional infection. During treatment, 3 horses developed high undulating pyrexia (39.6–40.9°C); horse 4 had febrile peaks >40°C and
Bacterial Meningitis After Sinus Surgery
was also administered metamizole (40 mg/kg IV). Three horses had tachycardia and tachypnea. Within 5–11 days (mean SD; 8.8 2.3 days) after initial surgery and 4–11 (6.6 2.7) days after last surgery, respectively, all horses had signs of acute, progressive neurologic disease. The most common clinical signs were apathy and depression (n ¼ 5). Ataxia and general coordination deficits (3) and proprioceptive deficits (2) were observed. Other neurologic abnormalities included abnormal head and neck posture while lying in the stall (1), blindness (1), partial loss of head and body sensitivity (1), and collapse (1). One mare was circling, had compulsive walking and intermittent head pressing. All horses continued to deteriorate within a short period, leading to recumbency. At this stage, nystagmus and seizures occurred in horse 4. With onset of neurologic signs, phenylbutazone administration in 3 horses was discontinued and flunixin meglumine (1.1 mg/kg IV twice daily) administered. Prednisolone (1 mg/kg orally once daily) was administered to horse 3. With progressive deterioration, a single dosage of dexamethasone (0.08 mg/kg IV) was administered to horse 5. Terminal seizures in horse 4 were controlled with butorphanol and diazepam. Radiographs of the neck and head in horse 5 ruled out bone trauma; however, on upper respiratory tract endoscopy there was a large accumulation of necrotic tissue in the left maxillary and frontal sinus. Hematologic and serum biochemical findings had evidence of hemoconcentration (n ¼ 2), severe leukocytosis (4; 14.6–46.4 103/mL [reference interval; 5–10 103/mL]) and neutrophilia (4), hypoproteinemia (2), hyperfibrinogenemia (2), and hyperglycemia (2). Blood cultures were not performed in any horse. Cerebrospinal fluid was collected from all horses: 2 ante‐ mortem from the lumbosacral space and in 3 horses, from the atlanto‐occipital space at death. All CSF specimens had turbidity and xanthochromia, indicating inflammation of the central nervous system. Neutrophilic pleocytosis and markedly increased total protein concentration were diagnosed in 2 samples. Cytologic examination and microbial culture in 2 specimens yielded negative results. Necropsy Findings None of the horses had evidence of systemic infection; however, meningoencephalitis was evident in all horses. The predominant findings were turbid and discolored CSF and malacia of cerebrum in all horses and purulent and necrotizing inflammation of the pituitary gland in horses 1, 2, 4, and 5. In horse 3, the cribriform plate had necrotizing inflammation and the bone surface was irregular. Malacia was present in the rhinencephalon. The inner lining of the sphenopalatine sinus was inflamed, but bony structures seemed macroscopically intact. In all other horses, no signs of bone deformations or lesions were detected. Sinusitis was present in all horses, but individual compartments were not examined in detail. Meningitis and meningoencephalitis, respectively, were confirmed histologically in 3 horses where tissue samples were taken. Histopathologic examination of horse 4 revealed massive neutrophilic infiltration of intracranial vascular walls and adjacent tissues as well as intraluminal presence of
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
699
Bacterial Meningitis After Sinus Surgery
Bach et al.
bacteria. Bacterial culture of pia mater in 2 horses yielded massive growth of Streptococcus equi ssp. zooepidemicus (horse 4) and methicillin resistant S. aureus (MRSA) in horse 1. In horse 3, bacteria could not be detected (Ziehl‐Nielsen and Grocott staining) in brain tissue.
DISCUSSION Bacterial meningitis is associated with high mortality. There are only a few reports of successfully treated bacterial meningitis or intracranial abscesses in adult horses.7–10 Toth et al.11 reported 96% mortality in 28 horses with meningitis or meningoencephalomyelitis. In horses with a history of bacterial meningitis secondary to infectious disease processes of the head, 100% mortality occurred.4,5 None of our horses survived. The closed‐ space localization of infection and the proximity to central nervous control centers increase the risk of a fatal outcome.12 Size, weight, and behavior of affected horses also complicate intensive care, especially in recumbent horses.11 There are 4 likely main pathways for infection caused by disease processes of the head: via osteitis/erosion of thin bones4,5,13; vascular spread (hematogenous‐metastatic, thrombophlebotic)4,5,13,14; along cranial nerves4,13; or by direct bacterial inoculation caused by (iatrogenic) head trauma.8,10,11 Ostitis/Erosion Pathologic fractures of the cribriform plate of horses with severe frontal sinusitis have been reported.11,15 Infection of the cranial cavity is also facilitated if the integrity of the cribriform plate has been compromised by adjacent infection, neoplasia, tumor‐like lesions, or (iatrogenic) trauma.16,17 The sphenopalatine sinus is a further predilection site, because the wall adjacent the cranial cavity is extremely thin18 and is in close proximity to the cavernous sinus (Fig 1). Ostitis erosions may predispose to intracranial injury including meningitis and related disorders.18–22 McCann et al.18 suggest CT, MRI, and sinoscopy to improve detection of bony perforation; however, diagnosis is difficult even with radiography.20,23,24 Fractures of these bony structures were not identified on radiographic or CT examination at hospital admission in horse 3. Necropsy findings and diagnosis of a space‐occupying process adjacent the ethmoturbinates and in the sphenopalatine sinus, as well as blurred bony contours on CT examination, make transmission through the cribriform plate very likely in case 3. Yet, diagnostic imaging techniques, or microscopic examination for detection of microlesions, were not performed post mortem.
Figure 1 The lamina cribrosa of the ethmoid bone (red outline) and the dorsal wall of the sphenopalatine sinus (orange outline) are the predilection sites for ostitis erosion transmission. From: Popesko (2007)41, modified, with permission by Priroda publishing, Bratislava, Slovakia.
sinus system with the facial veins that lie beyond the cranium.25–27 In horses, the dorsal and ventral (basal) dural venous sinus systems are not directly connected. The ventral venous sinus system seems more important in the pathogenesis of ascending meningitis. The cavernous sinus is the central reservoir of the ventral sinus system and surrounds the pituitary gland. The cavernous sinus bilaterally anastomoses with the extracranial ophthalmic plexus via the orbital fissure emissary veins.26,27 The ophthalmic plexus merges into the deep facial vein, which collects the blood from parts of the facial and upper dental area,27 from the orbital and nasal cavity, and from the nasal conchae.26 Because of the venous characteristics, spread of infection from the dentofacial area into the dural venous sinus system is possible25 either in a hematogenous‐metastatic or phlebitic manner14 (Fig 2). Given that purulent and necrotizing inflammation of the pituitary gland and intracranial phlebitis/bacteremia (horse 4) were identified but bony structures of the cranial vault, especially of the sphenopalatine sinus and cribriform plate, seemed macroscopically intact in horses 1, 2, 4, and 5, this hematogenous route of infection seems most likely for these cases; however, combinations of pathways are possible. Detailed morphologic examination of vessels and vascular relationships could substantiate thrombophlebitic spread of infection, as reported by Smith et al.4 Cranial Nerves
Vascular/Hematogenous Infection The intracranial venous system has characteristic anatomic features. The veins are not accompanied by arteries and open into dural venous sinuses. Both veins and dural venous sinuses lack a smooth muscle layer and valves, thus vasoconstriction is impeded and bidirectional blood flow is possible depending on vascular pressures. Emissary veins connect the intracranial
700
In ruminants, encephalitic listeriosis appears to result from migration of bacteria along the trigeminal nerve to the brainstem. Bacteria have been observed within neurons and axons and a mechanism for cell‐to‐cell spread has been postulated.28 Smith et al.4 hypothesized the possibility of ascending infections along the olfactory and optic nerve in horses based on finding infection and bacteria in close
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
Bach et al.
Bacterial Meningitis After Sinus Surgery
Figure 2 Schematic illustration of the vascular pathway of infection: the deep facial vein collects the venous blood from the dentofacial area (respective drainage areas in italic) and is connected to the cavernous sinus, which surrounds the pituitary gland. Because of venous characteristics, transmission of infection into the cranial vault is possible.
proximity to the cribriform plate, in the periorbital region, and the optic chiasm. Although findings of purulent infection on both sides of the cribriform plate and fungal elements along olfactory nerves indicate the possibility of ascending infection by this route, clear evidence of neuritis or continuous bacterial invasion of nerve tracts over their entire length was not documented. This was also true for the suggested correlation between bacteria in the periorbital tissues and microscopic abscesses in the optic chiasm, which could alternatively have been transmitted by previously affected meninges or the pituitary gland, which lie in close proximity. Furthermore, a combination of spread of infection along olfactory fibers and through a compromised cribriform plate seems more likely than an exclusively nerve associated transmission. Visual disturbances in horse 3 are most likely explained by the history of facial swelling, chronic sinusitis, and diagnosis of a space‐occupying mass. Chronic sphenopalatine sinusitis29 and different types of nasal and paranasal sinus tumors17 can affect the optic nerve. Ascending nerve infection cannot completely be ruled out, because morphologic examination of the optic nerve and the optic chiasm was not conducted. Head Trauma Traumatic injury to the skull with secondary meningitis or intracranial abscess8,10,11 and iatrogenic damage to the cranial
vault during surgical excision of dentigerous cysts has been reported.30–32 Surgical excision of tumors or tumor‐like lesions could result in similar complications. None of our horses had signs of head trauma ante‐ or postmortem. The question arises, whether the surgical procedures performed were the cause of, or at least triggered, meningitis in our horses or whether this complication of sinusitis would have occurred anyway. General predispositions for meningitis include immunocompromised states33 or septicemia,12 which may play a role in foals and in adult horses.13,34–36 There was no clinical or other evidence of immunodeficiency in our horses; however, specific testing was not performed. Horse 5 had transient pyrexia on admission but this resolved before surgery, although the possibility of this being associated with subsequent infection cannot be excluded. Most sinus surgery is not clean2 and all of our horses had at least 1 invasive surgical procedure resulting in considerable surgical trauma. Presence of necrotic tissue, inspissated pus and clotted blood are an ideal environment for bacterial growth. Although none of the horses had signs of superficial surgical site infection,37 the contaminated intrasinus environment may have contributed to development of meningitis. Waguespack et al.37 mention local necrosis and release of proteolytic enzymes as a mechanism for facilitating expansion into adjacent regions. Endotoxins and peptidases from injured tissues can activate vasoactive peptides, the clotting and
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
701
Bacterial Meningitis After Sinus Surgery
Bach et al.
fibrinolytic cascades, and alter systemic resistance. This seems especially interesting in the light of possible bacteremic/ phlebitic spread of infection. The relationship between intraoperative incidents and meningitis is unknown in our horses. Substantial hemorrhage (horses 2, 4) has been described as a major risk of sinus surgery2,6 leading to reduced visibility in the surgical field,6 to systemic disturbances, and a potential loss of immunoresistance.37 Hemorrhage increases the risk of incomplete tissue removal and inadvertent lacerations of delicate structures (e.g., cribriform plate, nerves). It is conspicuous that drainage was inadequate in 4 horses (1 and 2 [intraoperatively], 4 and 5 [postoperatively]). Blood clots, soft tissue swellings, and incompletely resected masses or cysts represent obstacles which can impede irrigation, resulting in increased pressure in the sinonasal system during flushing, such that devitalized tissues and delicate structures could be injured and bacterial invasion facilitated. Accumulation of infectious material because of insufficient drainage provides continuing nidus for infection. We are unaware of any study describing the effect of sinonasal irrigation on intracranial pressure. Head positioning affects intracranial pressure,38 and seizures in horses can result from increased intracranial pressure.12 Positioning with lowered head during general anesthesia in conjunction with high pressure flushing of the sinonasal system could have markedly increased intracranial pressure, leading to convulsions in horse 1. In horse 4, Streptococcus equi ssp. zooepidemicus isolated at necropsy is recognized as a meningitis causing pathogen in adult horses.13 In a previous sample from the sinuses of this horse, MRSA and ESBL E. coli were isolated and antibiotic therapy was discontinued. There is ample room for speculation as to whether continued antibiotic therapy may have saved this horse as no multidrug resistant organisms were found intracranially. The other 4 horses received antibiotics continuously, yet in 2 horses (2, 5) susceptibility testing was not performed. Interestingly, the initial culture from the sinuses of horse 1 yielded growth of Streptococcus ssp., whereas MRSA was isolated from the meninges at necropsy. Whether MRSA infection was present at the surgical site at the onset of meningitis is unknown. The mixed isolates from our cases appear to preclude a common virulent strain of bacterium, although some horses were eventually unresponsive to treatment. There are some empirical reports of successful antibiotic protocols in equine meningitis,4,10,39 and recommendations for appropriate treatment of bacterial meningitis are reported.9,12,13 Complications associated with human endoscopic endonasal sinus surgery have become rare.40 Although outcomes from human sinonasal surgery are difficult to compare with outcomes in horses, use of preoperative diagnostic imaging (CT, MRI) and increased use of minimally invasive surgical methods (e.g., transnasal sinoscopy; personal communication, Simhofer H, October 2012) might further reduce postoperative complications in horses. Meningitis is an uncommon but mostly fatal complication that can occur after sinus surgery in horses. The contributing cause(s) of meningitis in these horses is speculative and the small number of cases within this series makes it difficult to
702
draw conclusions concerning preventative measurements. However, risk factors likely include a combination of surgically traumatized tissue, compromised drainage, high irrigation pressures, anatomic proximity to the cranial vault and nerves, and the presence of multidrug resistant organisms. As soon as suspicious clinical signs such as hyperthermia, depression, or neurologic signs are encountered, a detailed neurologic evaluation including hematology, CSF analysis, microbial sampling, and sensitivity testing and exclusion of differential diagnoses is warranted, followed by appropriate aggressive therapy as indicated.
REFERENCES 1. Dixon PM, Parkin TD, Collins N, et al: Equine paranasal sinus disease: a long‐term study of 200 cases (1997–2009): treatments and long‐term results of treatments. Equine Vet J 2012;44:272– 276 2. Ahern BJ, Parente EJ: Surgical complications of equine upper respiratory tract. Vet Clin Equine 2009;24:465–484 3. Frees KE, Gaughan EM, Lillich JD, et al: Severe complication after administration of formalin for treatment of progressive ethmoidal hematoma in a horse. J Am Vet Med Assoc 2001;219:950–952 4. Smith JJ, Provost PJ, Paradis MR: Bacterial meningitis and brain abscesses secondary to infectious disease processes involving the head in horses: seven cases (1980–2001). J Am Vet Med Assoc 2004;224:739–742 5. Reilly L, Habecker P, Beech J, et al: Pituitary abscesses and basilar empyema in 4 horses. Equine Vet J 1994;26:424–426 6. Hart SK, Sullins KE: Evaluation of a novel post‐operative treatment for sinonasal disease in the horse (1996–2007). Equine Vet J 2011;43:24–29 7. Atherton RP, Mitchell EV, McKenzie HC, et al: Traumatic fracture of the basisphenoid and secondary bacterial meningitis in a Thoroughbred gelding. Equine Vet Educ 2007;19:359–364 8. Cornelisse CJ, Schott HC II, Lowrie CT, et al: Successful treatment of intracranial abscesses in 2 horses. J Vet Intern Med 2001;15:494–500 9. Mitchell E, Furr MO, McKenzie HC: Antimicrobial therapy for bacterial meningitis. Equine Vet Educ 2007;19:316–323 10. Newton SA: Suspected bacterial meningoencephalitis in two adult horses. Vet Rec 1998;142:665–669 11. Toth B, Aleman M, Nogradi N, et al: Meningitis and meningoencephalomyelitis in horses: 28 cases (1985–2010). J Am Vet Med Assoc 2012;240:580–587 12. Pellegrini‐Masini A, Livesey LC: Meningitis and encephalomyelitis in horses. Vet Clin Equine 2006;22:553– 589 13. Furr M: Bacterial infections of the central nervous system, in Furr M, Reed S (eds): Equine neurology. Ames, IA, Blackwell Publishing, 2008, pp 187–212 14. Lehnerdt G, Peraud A, Berghaus A, et al: Orbitale und intrakranielle Komplikationen akuter Sinusitiden. HNO 2010;59:75–88 15. Freeman DE: Sinus disease. Vet Clin Equine 2003;19:209–243
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
Bach et al.
Bacterial Meningitis After Sinus Surgery
16. Zaruby JF, Livesey MA, Percy DH: Ethmoid adenocarcinoma perforating the cribriform plate in the horse. Cornell Vet 1993;83:283–289
29. Barnett KC, Blunden AS, Dyson SJ, et al: Blindness, optic atrophy and sinusitis in the horse. Vet Ophthalmol 2008;11 (Suppl1):20–26
17. Head KW, Dixon PM: Equine nasal and paranasal sinus tumours. Part 1: review of the literature and tumor classification. Vet J 1999;157:261–278
30. Barakzai SZ, Dixon PM: Dentigerous cysts. Equine Vet Educ 2012;24:579–581
18. McCann JL, Dixon PM, Mayhew IG: Clinical anatomy of the equine sphenopalatine sinus. Equine Vet J 2004;36:466–472
31. Hunt RJ, Allen D, Mueller E: Intracranial trauma associated with extraction of a temporal ear tooth (dentigerous cyst) in a horse. Cornell Vet 1991;81:103–108
19. Riegg A: Squamous cell carcinoma involving the facial sinuses and air passages in a horse (clinical reports). Vet Med 1946;41:142–143
32. Cronau M, Gerhards H: Matiasek, K: Multiple dentigerous cysts in a 6‐year‐old chestnut warmblood gelding. A case report. Tierarztl Prax Grosstiere Nutztiere 2009;2:129–133
20. Behrens E, Schumaker J, Morris E: Contrast paranasal sinusograpy for evaluation of disease of the paranasal sinuses of five horses. Vet Radiol 1991;32:105–109
33. Brouwer MC, Tunkel AR, van de Beek D: Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010;23:467–492
21. Tremaine WH: A clinical and histopathological study of the equine upper respiratory tract disease. M. Phil. Thesis, University of Edinburgh, 1997
34. Pellegrini‐Masini A, Bentz AI, Johns IC, et al: Common variable immunodeficiency in three horses with presumptive bacterial meningitis. J Am Vet Med Assoc 2005;227:114–122
22. Dixon PM, Head KW: Equine nasal and paranasal sinus tumours: part 2: a contribution of 28 case reports. Vet J 1999;157:279–294
35. Clark EG, Turner AS, Boysen BG, et al: Listeriosis in an Arabian foal with combined immunodeficiency. J Am Vet Med Assoc 1978;172:363–366
23. Gerber H: Nasennebenhoehlen, in Wintzer HJ, (ed): Krankheiten des Pferdes: Ein Leitfaden fuer Studium und Praxis (ed 3). Berlin, Parey, 1999, pp 7–11 24. Taylor DS, Wisner ER, Kuesis BS, et al: Gas accumulation in the subarachnoid space resulting from blunt trauma to the occipital region of a horse. Vet Radiol Ultrasound 1993;34:191–193 25. Stoffel MH: Funktionelle Neuroanatomie für die Tiermedizin. Stuttgart, Enke, 2011, pp 117–120
36. Flaminio MJBF, Tallmadge RL, Salles‐Gomes COM, et al: Common variable immunodeficiency in horses is characterized by B cell depletion in primary and secondary lymphoid tissues. J Clin Immun 2009;29:107–116 37. Waguespack RW, Burba DJ, Moore RM: Surgical site infection and the use of antimicrobials, in Auer JA, Stick JA (eds): Equine surgery (ed 3). Philadelphia, PA, Saunders, 2006, pp 70–87
26. König HE, Liebich HG, Cerveny C: Nervensystem (systema nervorum), in König HE, Liebich HG (eds): Anatomie der Haussäugetiere: Lehrbuch und Farbatlas für Studium und Praxis, Bd II (Organe, Kreislauf‐ und Nervensystem. Stuttgart, Schattauer, 1999, pp 203–276
38. Moore RM, Trim CM: Effect of hypercapnia or xylacine on lateral ventricle and lumbosacral cerebrospinal fluid pressures in pentobarbital‐anesthetized horses. Vet Surg 1993;22:151–158
27. Seiferle E: Gefäßversorgung von Rückenmark und Gehirn, in Nickel R, Schummer A, Seiferle E (eds): Lehrbuch der Anatomie der Haustiere (ed 4). Stuttgart, Parey, 2004, pp 209–227
40. Siedek V, Pilzweger E, Betz C, et al: Complications in endonasal sinus surgery: a 5‐year retrospective study of 2596 patients. Eur Arch Otorhinolaryngol 2013;270:141–148
28. Morin DE: Brainstem and cranial nerve abnormalities: listeriosis, otitis media/interna and pituitary abscess syndrome. Vet Clin Food Anim 2004;20:243–273
41. Popesko P: Median section through cranial cavity, in Popesko P (ed): Atlas of topographical anatomy of domestic animals (ed 6). Stuttgart, Enke, 2007, p 138
39. Mitchell E, Furr MO, McKenzie HC: Bacterial meningitis in five mature horses. Equine Vet Educ 2006;18:249–255
Veterinary Surgery 43 (2014) 697–703 © Copyright 2014 by The American College of Veterinary Surgeons
703
