1
Bacterial and Fungal Disease of the CNS
Simon R Platt BVM&S MRCVS Dipl. ACVIM (Neurology) Dipl. ECVN
College of Veterinary Medicine University of Georgia, Athens, USA
Introduction
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
Brain Abscess n Liquefactive necrosis 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 1981 1. 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
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
Clinical Signs in Dogs n Acute to chronic n Progressive 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
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
Diagnosis of Inflammatory Disease
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
n Skull radiography n Computed tomography n Magnetic resonance n Cerebrospinal fluid n + / - Electroencephalography n +/- Tissue biopsy????
CSF ANALYSIS 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
3
CSF ANALYSIS
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
CT Scan
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)
MRI Brain Abscess n T1W
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
Bahn et al J Kor Neurosurg Soc 2010
2 yr Old Mix CN – CT & MRI
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
Bacterial Disease
n CSF tap imperative n Possibly purulent 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
2-3 months oral therapy if no surgery n Ampicillin n Clavulanated Amoxicillin n Enrofloxacin n Third generation cephalosporins n Metronidazole n Trimethoprim-sulphadiazine n Doxycycline
First 2-3 days
Empirical therapy of brain abscess
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%
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
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
Cryptococcal Encephalomyelitis
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 200-300/il n Median wbc 21-67/ul n Median protein 39-161 mg/dl
n Mixed or granulomatous pleocytosis in dogs n Neutrophilic in cats n Cryptococcal capsular antigen in serum or
CSF
6
Cryptococcosis n Meningitis versus gelatinous
pseudocysts n Dilation of Virchow-Robin Space
n MRI characteristics depend on whether there is meningo-encephalitis, 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
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
Aspergillus Encephalitis
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 2015
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
Top Related