Introduction. Brain Abscess. Stages of Abscess Formation. Pathogenesis of Hematogneous Bacterial CNS Infection. Entry of CNS Infections

Transcription

1 Bacterial and Fungal Disease of the CNS Introduction Simon R Platt BVM&S MRCVS Dipl. ACVIM (Neurology) Dipl. ECVN College of Veterinary Medicine University of Georgia, Athens, USA n Meningitis / Encephalitis / Myelitis n Abscess enclosed collection of liquefied tissue known as pus; can be sterile or septic n Granuloma mass of chronically inflamed tissue; can infectious or sterile n Empyema pus in a cavity, space or potential space n Liquefactive necrosis Brain Abscess n Surrounding brain is edematous n May present with progressive focal deficits & general signs of raised intracranial pressure n CSF may contain normal to slight increased number of wbcs and increased protein n May lead to herniation or rupture into CSF Juliana de Castro Cosme et al, Rev Bras Med Vet 2015 Stages of Abscess Formation n Britt et al; Canine model - J of Neurosurg Early cerebritis days 1-3; perivascular inflammation / neutrophil invasion / edema 2. Late cerebritis days 4-9; central area of necrosis and peripheral fibroblast accumulation 3. Early capsule days 10-14; well vascularized tissue with further fibroblast migration 4. Late capsule - >day 14; collagen fiber and granulation tissue deposition thickens capsule Entry of CNS Infections n Hematogenous spread n most common n Especially if immunosuppressed n Direct implantation usually traumatic n Local extension secondary to infection in ear / nose / sinus / tooth root Pathogenesis of Hematogneous Bacterial CNS Infection 1. Colonization in body system / adhesion to mucosa 2. Mucosal invasion & penetration into bloodstream 3. Cross the blood brain barrier usually at endothelium of choroid plexus into ventricular fluid 4. Multiply in CSF / inflammatory response 5. Cerebral edema 1

2 Otogenic Origin CNS Infections n Meningitis and abscesses n Associated with long standing otitis media-interna n Can be acute or chronic in onset n CT can demonstrate skull defects n MRI ideal for caudal fossa soft tissue abnormalities n Acute to chronic n Progressive Clinical Signs in Dogs n Asymmetric, multifocal n Cranial nerve / Visual deficits n Altered mentation n Paresis n Seizures n Postural reaction deficits n Neck pain n Pyrexia DIFFERENTIAL DIAGNOSIS for Inflammatory Disease Diagnosis of Inflammatory Disease Subacute-chronic, progressive, asymmetric +- pain n V Vascular n I n T Trauma, Toxin n A Anomalous (developmental) n M Metabolic n I Idiopathic n N Neoplastic, Nutritional n D Degenerative Minimum Data Base n Good history travel / in contacts? n Physical exam n Neurological exam n Fundic exam n Hematology / Serum chemistry n Urinalysis n Bile acids n Thoracic and abdominal imaging n Infectious disease titers / PCR Diagnosis of Inflammatory Disease CSF ANALYSIS n Skull radiography n Computed tomography n Magnetic resonance n Cerebrospinal fluid n + / - Electroencephalography n +/- Tissue biopsy???? n Requires anesthesia n Requires technical experience n Requires immediate laboratory analysis n Add hetastarch or autologous serum and store at 4 C n Rarely specific but very sensitive 2

3 CSF ANALYSIS CT Scan n Ideal to obtain cisternal and lumbar samples n Subjective qualities n Cell count n Protein level n Cytology n Titers & PCR n Culture n Electrophoresis n Excellent for imaging bone n CT can demonstrate significant abnormalities of parenchyma n Contrast enhancement can help n Poor imaging of caudal fossa Bilderback et al J Vet Emerg Crit Care 2009 MRI n Excellent soft tissue detail n Extent of disease can be assessed n Not specific n 76% sensitive compared to CSF (Lamb 2005) n T1W MRI Brain Abscess n Central hypointensity (hyperintense to CSF) n Peripheral low intensity vasogenic edema n Ring enhancement n +- ventriculitis and hydrocephalus n T2W / FLAIR n Central hyperintensity (hypointense to CSF) n Does not attenuate on FLAIR n Peripheral high intensity vasogenic edema n Abscess capsule may be visible as intermediate to slightly low signal thin rim n Differentials include neoplasia, infarction, hematoma, granuloma 2 yr Old Mix CN CT & MRI Bahn et al J Kor Neurosurg Soc

4 Bacterial Disease n Dogs can have infection spread from ear / nose / skin / abdomen n Plethora of organisms staph / strep / pasteurella / actinomyces/ nocardia / e. coli n 11/23 pyrexic in one study & 5/23 had neck pain n Brain > Spine (empyema) n Can lead to secondary hydrocephalus n Guarded prognosis n CSF tap imperative n Possibly purulent Bacterial Disease n Neutrophilic pleocytosis -70% dogs (18-10,850) n 7% humans /2-16% dogs no pleocytosis n Multiplex PCR bacterial genome n Not affected by prior antibiotics n Gram stain n Culture (13-31% positive in dogs) n CSF lactate levels Antibiotic Therapy Empirical therapy of brain abscess 2-3 months oral therapy if no surgery n Ampicillin First 2-3 days n Clavulanated Amoxicillin n Enrofloxacin n Third generation cephalosporins n Metronidazole n Trimethoprim-sulphadiazine n Doxycycline Steroidal Therapy n Decreases host defense and decreases penetration of some antimicrobials n May result in improvement of neuro signs n Useful if: n Associated edema and mass effect n Progressive neuro deterioration n Short term & anti-inflammatory doses n Start before or same time as antibiotics Surgical Therapy n Optimal approach to humans with bacterial abscess n Aspiration after bur-hole placement or complete excision with craniotomy n Intra-operative ultrasound assisted n Bulla osteotomy if otogenic n In humans, recurrence rates after aspiration 0-24% 4

5 Indications for Initial Surgical Treatment n Significant mass effect n (>2.5cm diameter) n Proximity to ventricle n Elevated ICP n Poor neuro status n Traumatic origin n Fungal abscess n Multiloculated Pus Aspirated - What Next? Stains Gram stain Acid-fast stain for mycobacterium Special fungal stains (methenamine silver) Cultures Routine cultures aerobic / anaerobic Fungal cultures Treatment of Empyema Fungal Infections of the CNS n Usually associated with immunosuppression due to drugs, age, breed or other diseases n Mostly hematogenous dissemination n Rare direct extension (mucormycosis) n Yeasts - Leptomeningitis n Hyphae - Hemorrhagic infarcts From: Neuropathology Illustrated 1.0 Cryptococcal Encephalomyelitis Cryptococcal Encephalomyelitis n Common fungal CNS disease n May also involve eyes, nose or skin n C. neoformans (dogs) & gattii (cats) n Spread to CNS from nose or blood n 6-42% cats n 26-68% dogs n Often diffuse / multifocal neuro signs n Neck pain in dogs and TL pain in cats n Culture and Ag testing is necessary but not 100% sensitive n Organisms not always in CSF n 9/11 cats and 11/15 dogs n CSF analysis variable but cytology essential n Mean wbc /il n Median wbc 21-67/ul n Median protein mg/dl n Mixed or granulomatous pleocytosis in dogs n Neutrophilic in cats n Cryptococcal capsular antigen in serum or CSF 5

6 Cryptococcosis n Meningitis versus gelatinous pseudocysts n Dilation of Virchow-Robin Space n MRI characteristics depend on whether there is meningoencephalitis, pseudocysts or cryptococcomas Cryptococcal Encephalomyelitis n Fluconazole 5-15 mg/kg PO bid for 6 months >>Itraconazole n Amphotericin B SQ 16mg/kg n Glucocorticoid use after diagnosis improves 10 day survival n Altered mentation associated with a negative outcome n 32% cats and dogs remission >1yr n 55% dogs successfully treated but recrudesce n > 6mo median survival possible if survive >4 days after diagnosis Sykes et al J Vet Int Med 2010 O Brien CR, et al: Aust Vet J 2006 Aspergillus Encephalitis Aspergillus Encephalitis n Soil or plant saprophyte causing disseminated infection n A. fumigatus / flavus sino-nasal / lung n A. terreus / deflectus - disseminated n More common in GSDs n Often young dogs (median 3yrs) n Mostly females? n May be extension of nasal dz n Multifocal / often vestibular n Galactomannan EIA test n Urine, blood, CSF, tissue culture n CSF n Neutrophilic pleocytosis n Increased protein n MRI may be normal n Mass lesions n Multifocal n Contrast enhancing n Hemorrhagic infarctions Taylor et al J Vet Int Med 2015 Aspergillus Encephalitis n No topical treatment if cribriform is damaged n Voriconazole 5mg/kg PO bid n +- terbinafine 6.25mg/kg PO bid n Itraconazole 5mg/kg PO bid n +- anti-inflammatory steroids n Disseminated disease carries poor prognosis (0-25 mo) Coccidioidomycosis n Soil organisms endemic to SW USA n Inhalation leads to lung infections n Osteomyelitis in dogs n Skin and disseminated in cats n Diffuse or focal CNS disease n 2/7 animals had normal CSF wbc count n MRI lesions could be intra or extra-axial granulomas n Need histo / cyto diagnosis Bentley et al Vet Radiol US

7 Summary n Bacterial and fungal CNS disease has a poor prognosis n Originates locally or systemically n May form focal or diffuse lesions n May require surgery and or medical therapy n Requires a combination of imaging and CSF analysis to get close to diagnosis n Only definitive is often histopathology 7