A case of cavernous sinus thrombosis caused by Dialister pneumosintes , Slackia exigua and Prevotella baroniae

Received 5 April 2014 Accepted 6 July 2014 Department of Neurosurgery, Tsukuba Medical Center Hospital, 1-3-1 Amakubo, Tsukuba, Ibaraki 305-8558, Japan Department of Infectious Diseases, Department of Medicine, Tsukuba Medical Center Hospital, 1-3-1 Amakubo, Tsukuba, Ibaraki 305-8558, Japan Miroku Medical Laboratory Inc., 659-2 Innai, Saku, Nagano 384-2201, Japan Department of Radiology, Tsukuba Medical Center Hospital, 1-3-1 Amakubo, Tsukuba, Ibaraki 305-8558, Japan Department of Neurosurgery, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki 305-8576, Japan


Introduction
Cavernous sinus thrombosis (CST) is a rare manifestation of cerebral venous thrombosis.CST causes several serious complications because the cranial nerves and internal carotid artery run through the lumen (Ebright et al., 2001), and accounts for 1.3 % of all cerebral venous thrombosis (Ferro et al., 2004).Mortality is reportedly 13 % and morbidity 23 % in previous case series (Yarington, 1997).
Unlike other cerebral venous thromboses, for which malignancy, pregnancy, collagen diseases, and trauma are the main aetiologies (Filippidis et al., 2009), most cases of CST have occurred associated with bacterial infections (Desa & Green, 2012).Staphylococcus aureus is isolated in two-thirds of CST cases, and Streptococcus pneumoniae is occasionally identified as an unusual presentation of pneumococcal infections (Southwick et al., 1986;Thatai et al., 1992).Anaerobes can also be causative pathogens (Palestro et al., 1986;Chang et al., 2004), but precise identification is rarely successful with conventional methods.
Herein we report a case of CST caused by Dialister pneumosintes, Slackia exigua and Prevotella baroniae, which are oral anaerobes that we determined using 16S rRNA sequencing.

Case report
An 82-year-old previously self-supported Japanese woman was transferred to our hospital with acute onset of impaired consciousness.She had been healthy until the morning of the day of admission without preceding symptoms, but was drowsy and unable to locate the toilet at home when her son returned in the afternoon.Her consciousness rapidly deteriorated during transportation and she had become unresponsive soon after arriving at our emergency department.She had a history of right upper dental caries before visiting our hospital, but otherwise had no past medical history.At our initial evaluation, the Glasgow Coma Scale value was 6 (E1V1M4) and her body temperature was 37.4 u C.There were no remarkable findings on chest or abdominal examinations.Neurological examination revealed conjugate deviation to the right side, and manual muscle testing was 0/5 on the left upper limb and 2/5 on the left lower limb.Other physical characteristics of significance were swelling of her right cheek and poor hygiene in her mouth, with dental caries in her upper right teeth.Laboratory analysis showed a white blood cell count of 41 600 ml 21 and a C-reactive protein level of 10.5 mg dl 21 .Functional indicators of kidney and liver, electrolyte levels, prothrombin time, and activated partial thromboplastin time were unremarkable.Computed tomography (CT) of the brain (Fig. 1a) showed right intracranial haemorrhage ranging from the right external capsule to the temporal lobe, and relatively widespread oedema around the haemorrhage, the distribution of which was inconsistent with the anatomical arterial location.Further investigation was performed with enhanced brain CT, which showed a low-density area (316967 mm) in the right masticator space (Fig. 1b), poor enhancement of the right cavernous sinus compared with the left cavernous sinus (Fig. 1c), and intermittent defect in the right superior ophthalmic vein (Fig. 1d).Based on the presence of thrombi in the sinus and vein and an abscess in the right masticator space, right CST was diagnosed.Intravenous ampicillin-sulbactam with anticoagulant therapy was administered after evaluation.Two sets of blood cultures were incubated with the BacT/ ALERT system (bioMe ´rieux), and positive signals were obtained in both of the anaerobic bottles after 78 and 86 h.No positive signals were obtained from the aerobic bottles.Direct Gram staining showed Gram-positive and Gramnegative rods.Three different colony types (Gram-positive rods and two kinds of Gram-negative rods) were obtained on 5 % sheep blood agar plates from two sets of blood culture bottles after 96 h of anaerobic incubation at 35 u C in an anaerobic chamber.One of the two Gram-negative rods was initially classified as Bacteroides uniformis by BBL Crystal ANR (Becton Dickinson) and API 20A (bioMe ´rieux).However, we could not microbiologically identify the other two bacteria with conventional phenotypic methods.Partial 16S rRNA gene sequencing using the ABI PRISM Big Dye Terminator Cycle Sequencing kit v3.1 (Applied Biosystems) was therefore performed, and the consensus sequence had the highest similarity to D. pneumosintes (100 % match; 847/847 bp; GenBank accession number HM 596297) and S. exigua ATCC 700122 (99.7 % match; 770/772 bp; GenBank accession number AF101240).We also performed sequence analysis for the Gram-negative rod initially considered as B. uniformis, and this was genetically classified as P. baroniae based on GenBank database searches (99.8 % match; 822/824 bp compared with P. baroniae strain E9.33, GenBank accession number AY840553).D. pneumosintes, S. exigua and P. baroniae bacteraemia was ultimately diagnosed.The MIC of ampicillin-sulbactam against P. baroniae was measured as #4 mg ml -1 with Dry Plate (Eiken Chemical Company), but we could not measure antimicrobial susceptibilities of D. pneumosintes and S. exigua because of their slow rate of growth.
Anticoagulant therapy was discontinued on day 34 because of rectal bleeding, and ampicillin-sulbactam was continued for 61 days with clinical improvement.The patient was discharged on day 108 after hospitalization.Owing to the sequelae of cerebral haemorrhage, she needed physical assistance, and her physical status at discharge was recorded as Grade 4 based on the modified Rankin Scale.

Discussion
We report a life-threatening CST with a mixed anaerobic infection.In this case we identified three anaerobes (D. pneumosintes, S. exigua and P. baroniae), all of are oral microbes whose molecular features were established recently (Doan et al., 2000;Downes et al., 2005;Moore & Moore, 1994;Wade et al., 1999).They have been associated with periodontal infections (Booth et al., 2004;Contreras et al., 2000;Downes et al., 2001;Rocas et al., 2010;Sakamoto et al., 2006;Siqueira & Rocas, 2009), but are rarely isolated from extra-oral infections.There has been one case of pneumonia (Bahrani-Mougeot et al., 2007), one of sinusitis (Drago et al., 2013), and cases of brain abscess (Rousee et al., 2002) with D. pneumosintes; and a case of meningitis (Bukki et al., 2011), cases of wound infections (Kim et al., 2010), and a case of infective endocarditis (Woo et al., 2004) with S. exigua.To our knowledge, none of these anaerobes has been reported as a causative pathogen of CST.We therefore describe the first case of CST associated with D. pneumosintes, S. exigua and P. baroniae, as confirmed by two sets of blood cultures.These organisms could be easily missed when standard protocols are used because of their fastidious and slow growth, and 16S rRNA sequence analysis is required for precise identification.Thus, these and other oral anaerobes might be more frequent causes of medically important infections than is currently recognized.
Regarding the diagnosis of CST, radiological signs of cerebral haemorrhage caused by cerebral venous thrombosis are not recognized in daily practice, so CST also tends to be under-diagnosed among patients with cerebral haemorrhage (Girot et al., 2007).In this case the haemorrhage in our patient was patchy, and peripheral oedematous change was apparent in comparison with typical acute intracranial haemorrhage.In addition, the haemorrhage overlapped several territories of intra-cerebral arteries (precentral artery, insular branches of middle cerebral artery, and posterior temporal artery).These are key features of cerebral haemorrhage caused by cerebral venous thrombosis (Bakac & Wardlaw, 1997), leading us to suspect the possibility of cerebral venous thrombosis in our patient.CST has been known to be frequently missed by non-enhanced CT with traditional section thickness (Chen et al., 2006), so thin-section enhanced CT should be performed.
A limitation of this report concerns the fact that we did not perform an invasive procedure or dental intervention to treat the abscess and dental caries during hospitalization.We considered aspiration therapy; however, as most of the abscess was located near or within the venous system, we chose antimicrobial therapy along with blood pressure and seizure control for CST and cerebral haemorrhage.A favorable response allowed us to continue these conservative therapies.However, it is possible that part of the abscess (Fig. 1b; size 316967 mm) could be aspirated percutaneously, which might shorten the duration of antimicrobial therapy, while dental intervention might provide the diagnosis for the route of infection.
We have reported a case of CST caused by D. pneumosintes, S. exigua and P. baroniae.CST should be considered in cases of unusual distribution of cerebral haemorrhage, especially with systemic inflammatory response syndrome.

Fig. 1 .
Fig. 1.CT on admission showed intracranial haemorrhage ranging from the right external capsule to the temporal lobe, with relatively widespread oedema around the haemorrhage (a).Initial enhanced CT showed an abscess in the right masticator space (b), poor enhancement of the right cavernous sinus (c), and intermittent defect in the right superior ophthalmic vein, representing thrombosis (d).