CNS INFECTION FOR NEUROSURGEON

1. Dr. Shahnawaz Alam
Guided by:-Dr. Vikas Chandra Jha
HOD Neurosurgery
Moderated by:-Dr. Saraj kumar Singh
Asst.Prof. (Dept. of Neurosurgery)
Infections in Neurosurgery

2. Outline
• Basic Science of CNS Infections
• Postoperative Infections of CNS
• Brain Abscess
• Meningitis and Encephalitis
• Use and Misuse of Antibiotics in Neurosurgery
• AIDS & Parasitic Infections of CNS

3. • Immune effectors: astrocytes and microglia
• Varying degrees of both structural and functional damage to CNS
• Others: matrix metalloproteinases enzymes/Dysregulation of glutamate
metabolism
• Implicated in many CNS ds.-infections, ischemic or traumatic injury, and
autoimmune disorders
• BBB is rich in potential substrates for MMPs, including type IV collagen,
fibronectin, and laminin; MMP degradation of the BBB may favor
transmigration of leukocytes as well as the movement of macromolecules
and water, thus contributing to brain edema
• MMPs are potential targets for therapeutic interventions
Basic Science of CNS Infections

4. CLASSIFICATION
• Anatomy of the infection (parenchymal, meningeal, parameningeal)
• Presence of space-occupying lesions (e.g. abscess, empyema)
• Diffuse inflammation (e.g. meningitis, encephalitis)
• Also a/c to etiology
• Pathogens enter the CNS directly (e.g., through trauma, neurosurgery),
/Via BBB/CSFB (e.g., bacterial meningitis caused by Escherichia coli), /
via retrograde transport along neural structures (e.g., rabies)
• Iatrogenic routes are more relevant to the neurosurgeon
• Perioperative breeches in structural barriers protecting the CNS (scalp,
cranium, meninges), implantation of foreign bodies (e.g., cerebrospinal
fluid [CSF] shunts, dural implants, electrodes, spinal hardware), and
breeches in mucosal defenses (e.g., intubation, vessel catheterization)

5.  MICROGLIA; several different states
• Resting microglia -Small cells with few surface markers & prominent thin branches
• Stimuli activate microglia-Cellular debris from CNS damage, particularly free ATP- Ameboid
cells
• Receptors expressed by microglia includes Toll-like receptors/a cytosolic “alarm system”
exists in microglia in the form of nucleotide-binding oligomerization domain 2 (NOD2)
• NOD2 recognizes a common motif in bacterial peptidoglycan from both gram -/+
• NO synthesis and a respiratory burst, leading to the formation of peroxynitrite (ONOO−), a
highly toxic product capable of damaging both host and pathogen/superoxide anion (O2−)
• Phagocytes in the CNS under both physiologic and pathophysiologic conditions
• Microglia also produce factors that support glial and neuronal cells/APC
• Downregulate these proinflammatory responses

6.  Astrocytes; Resident glial cells derived from neuroectoderm;“nurse” cells for
neurons
• star-shaped morphology & GFAP
• Maintain BBB/participate in the immunologic processes/targets of bacterial invasion
• Expression of OmpA by pathogenic E. coli strains significantly enhances E. coli invasion
of astrocytes
• GBS also invades astrocytes -death via expression of β-hemolysin/cytotoxin
• Pneumolysin (Ply)-structural and functional changes-tissue injury and brain edema
• Main source of IL-6 production in the CNS
• HIV gp120 reduces astrocyte expression of glutamine synthase, and patients with HIV-
associated dementia have higher brain glutamate levels
• Balance of CNS protection/ destruction during infection by secretion of MMPs

7. Postoperative Infections of the Head and Brain
• Diagnosis of infection after craniotomy is often challenging
• superficial incisional infections-skin and s.c tissue
• deep incisional infections-subgaleal space and bone flap
• Deep organ space infections-subdural empyema, brain abscess /meningitis/ventriculitis
• superficial infections-60% of SSIs after craniotomy/Meningitis-mc deep organ space
infection,22% /others;subdural empyema and brain abscess-14%
• Infections after craniotomy are most commonly associated with gram-positive bacteria-S.
aureus, and conS

8. • Majority of post-op infections- patient’s
skin
• Host defense mechanisms impaired in pt.
undergoing craniotomy
• Brain-relatively immune privileged
site/low levels of Abs & C -brain less
efficient than other organs
• Post-op CSF leakage and early subsequent
reoperation
• Placement of drains or icp monitors, poor
neurological status, paranasal sinus entry,
foreign body implantation
RISK FACTORS FOR INFECTION AND PREVENTIVE STRATEGIES

9. Role of Pre-op antibiotics in reducing the
incidence of SSIs after craniotomy
• The Surgical Care Improvement Project (SCIP) outlines the following 3 performance
measures for monitoring appropriate antimicrobial prophylaxis use:
1.selection of an appropriate antibiotic,
2.adminstration within 1 hour before incision
3.discontinuation within 24 hours after surgery is completed
• Choice of an agent-narrow spectrum;guided by institutional data on frequently
recovered pathogens and their resistance profiles
• For clean neurosurgical procedures, a single dose of cefazolin is recommended
• Vancomycin –MRSA/β-lactam allergy
• Antibiotics with short t1/2 such as cefazolin should be readministered every 3 to 4 hrs
during prolonged surgery
• Risk factors for MRSA: male, malignancy, DM, prior MRSA infection, immunosuppressed &
traumatic injury
• Other: surgical site preparation and environmental control within the operating room
• any hair removal that is performed should be done as close to the time of surgery as
possible
• use of high-efficiency particulate air (HEPA) filters

10. PRINCIPLES OF TREATMENT
•Postoperative infections tend to be particularly difficult to resolve because of the complex
anatomic changes resulting from craniotomy
•Early and decisive intervention is critical to limit morbidity, and the keystone of successful
treatment is effective source control (i.e., drainage of abscesses and infected fluid
collections and debridement of necrotic tissue)
•Bactericidal rather than bacteriostatic agents are generally preferred
•Most antibiotic agents enter CNS mostly by passive diffusion down a concentration
gradient, with physical barriers BBB and blood-CSF barriers functioning as the primary
determinants of drug distribution
•Inflammation at the site of infection may facilitate entry of drugs across these barriers and
into the brain
•Other inherent physiochemical properties: Mwt., lipophilicity, PPB & ionization state
•Ultimately, adequate dosing - minimal bactericidal concentration [MBC]).

11. • Empirical regimens for postcraniotomy infections: vancomycin + 3rd /4th gen. cephalosporin with
antipseudomonal activity (e.g., ceftazidime, cefepime) + metronidazole (anaerobic)
• carbapenem (e.g., meropenem) may be substituted for the combination of a third-generation
cephalosporin and metronidazole (Gram - & anaerobes)
• Imipenem-increased seizure risk relative to meropenem (and other β-lactams)
• β-Lactam antibiotics (penicillins, cephalosporins, carbapenems) have poor penetration into the
CSF in the absence of meningeal inflammation, but higher systemic doses can result in
therapeutic CSF concentrations
• 3rd /4th gen. cephalosporin (specifically cefotaxime, ceftriaxone, and ceftazidime) are often used
for the treatment of CNS and postcraniotomy infections because of their low toxicity and
excellent activity
• High-dose β-lactamase inhibitors such as sulbactam and tazobactam are also effective in
protecting the coadministered penicillin agent
• β-lactam antibiotics-proconvulsive- use via intraventricular injection not recommended
• Intraventricular antibiotic administration bypasses BBB, can achieve much higher CSF
concentrations than systemic administration;asst. with neurotoxicity

12.  CSF Shunt Infections: The Role of Biofilms
• Perioperative contamination/Wound dehiscence over the shunt
/Hematogenous seeding/Distal port contamination
• Biofilm formation occurs with both infection and colonization of
prosthetic medical devices
• Biofilms are in a stationary phase of growth-less susceptible to
antibiotics/less permeable to most antibiotics/prosthetic devices lack a
vascular supply
• Coagulase-negative staphylococci (CoNS)-notorious for their ability to
form biofilm on prosthetic devices
• Soon after placement, bioprosthetic materials are coated with host
proteins, which serve as receptors for bacterial adhesins k/a “microbial
surface components recognizing adhesive matrix molecules,” or
MSCRAMMs- CoNS initiate biofilm formation almost immediately
• Transition state between planktonic and sessile bacteria in biofilms
known as quorum sensing
• Dormant microbes (sessile) within the biofilm are up to a 1000 times
more tolerant of [most] antimicrobial agents than their free-living
(planktonic)
S. epidermidis biofilm formation on a
catheter surface. Note the deposition of
extracellular matrix,manifested as a
complex web of material around and
between microcolonies

13. SUPERFICIAL INCISIONAL INFECTIONS
• extend from the skin to the epidural space.
• May extend to the underlying bone flap and through the dura
• repeat operative intervention, poor tissue quality, impaired vascular supply, radiation injury,
nutritional deficiencies, and the presence of foreign bodies
• manifests as local erythema, swelling, and tenderness at the craniotomy site with possible
suppurative drainage
• With progressive infection, systemic signs such as malaise, fever, and chills may develop
• The most common pathogenic agents of superficial wound infections are gram-positive cocci,
including S. aureus, coagulase-negative staphylococci, and P. acnes
• clinically apparent; however, CT or MRI reveal fluid collections in the subgaleal or epidural
space/extension/bone flap osteomylitis/ identifying possible precipitating factors
• Measurement of ESR/CRP concentration may provide some assistance in detecting infection
and monitoring the response to therapy
• normally elevated after craniotomy and return toward baseline by the 5th POD
• nonspecific, prolonged elevation or a secondary increase in their levels may indicate the
development of infection
• Hyperbaric oxygen (HBO)/local rotational or pedicled flaps or vascularized myocutaneous free
flaps -chronic postoperative infections

14. Purulent drainage from a superficially infected
craniotomy incision with surrounding erythema
Skin breakdown at the inferior aspect of the craniotomy
incision with exposed titanium hardware
A.Surgical debridement of a superficial postcraniotomy infection in a patient who had undergone multiple craniotomies and
radiation treatments for malignancy. There is spread of infection to the underlying bone flap, with erosion and adjacent
purulent material in the epidural space.
B.Epidural infection with contamination of the undersurface of the devascularized bone flap.

15.  DEEP INCISIONAL INFECTIONS: SUBGALEAL SPACE AND BONE FLAP
• A high index of suspicion
• majority d/t commensal skin flora infection of autogenous cranioplasties after
decompressive craniectomy; however, a significant proportion are due to
nosocomial gram-positive and gram-negative organisms
• CT and MRI studies may show the presence of subgaleal or epidural infection with
bone flap destruction suggestive of osteomyelitis
• Treatment options: antibiotic therapy alone/surgical debridement with removal of
the bone flap/debridement with replacement of the bone flap or other cranioplasty
material such as titanium mesh
• Removal of the infected bone flap followed by delayed cranioplasty offers the best
chance of clearing the initial infection/ multiple surgical interventions
• Several case series have reported clinical resolution of infection with preservation of
the bone flap
• In Other study successful resolution of infection in patients treated with immediate
titanium mesh cranioplasty at the time of initial surgical debridement

16. A, Axial computed tomography (CT) scan demonstrating
erosion of bone flap (asterisk) indicative of
osteomyelitis. B, Coronal CT scan showing failure of
titanium screws with surrounding bone lucency (arrow)
A, Debridement of the epidural infection and removal of the
infected bone flap and hardware. B, Immediate titanium mesh
cranioplasty performed at the time of infection debridement.
A, T1-weighted axial magnetic resonance (MR) image reveals a hyperintense subdural fluid collection that
developed after craniotomy for aneurysm repair. The fluid collection enhances peripherally with gadolinium
(B) and, because of higher protein content, exhibits increased signal intensity on fluid-attenuated inversion
recovery (FLAIR) MR sequences (C) relative to cerebrospinal fluid. A craniotomy was performed to drain the
collection, and frank purulence was encountered in the subdural space.

17.  Subdural Empyema
• spontaneously subdural empyema- fever and headache, followed by the rapid development of focal
neurological deficits, altered mental status, and seizures/rarely in subdural empyema develops after
craniotomy;Insidious course
• Febrile 33%;seizure 25% & 85% without headache;/MC findings- superficial wound infection/In 50%
;occurr more than 1 month after the craniotomy
Diagnostic Imaging and Laboratory Data
• extra-axial fluid collections are commonly noted on postoperative imaging studies
• NCCT demonstrates a crescent-shaped fluid collection that is slightly more dense than CSF and located
beneath the craniotomy flap or adjacent to the falx
• Increased signal intensity on T1-w and fluid-attenuated inversion recovery (FLAIR) MRI sequences
because of the increased protein concentration of an empyema relative to CSF. Peripheral enhancement
of the fluid collection is common
• presence of restricted diffusion on MRI may be helpful
• Progressive enlargement of the fluid collection or unexplained edema in adjacent cerebral cortex
• Laboratory data –nonspecific; LP-C/I
Treatment
• Goals of surgery are to evacuate the purulent collection completely/adequate decompression of the
brain
• optimal surgical approach (craniotomy versus bur-hole drainage) is debated, craniotomy is generally
advocated
• Empirical antibiotic therapy should be started Early
DEEP ORGAN SPACE INFECTIONS

18. • Newer agents useful for the treatment of resistant staphylococcal infections include
linezolid and daptomycin
• It has excellent bioavailability, i.v ior orally; adr- myelosuppression and irreversible
peripheral neuropathy
• Rifampin is a broad-spectrum antimicrobial ;role in the adjunctive Rx of bone flap
osteomyelitis or infections associated with foreign body implantation
• Rifampin-penetrate biofilms and kill organisms in the sessile phase of growth/used in
combination/cytochrome –p enzyme +
• Fluoroquinolones (levofloxacin, ciprofloxacin, moxifloxacin) are attractive agents for
the treatment of CNS infection because of their lipophilicity and low molecular
weight./High resistant/increase seizure threshold
• Aminoglycosides have excellent activity against aerobic gram-negative bacilli,
including P. aeruginosa, as well as synergistic activity with β-lactams against aerobic
gram-positive cocci

19. Brain Abscess: Pus in the
Parenchyma
• Space-occupying purulent infections
within the substance of the brain
• Clinically, the classic triad of headache,
fever, and focal neurological deficit is
rarely present; s/s of postop abscess
nonspecific; expanding, irritative mass
lesion-altered LOC, N/V & seizures 20%
• Microbiology related to the primary
source of the abscess
• staphylococci and Enterobacteriaceae-
direct inoculation from trauma or
neurosurgical procedures

20. • Abrupt worsening of preexisting headache asst.
with new onset of meningismus -
Intraventricular rupture of a brain abscess
(IVROBA)
• manifest sudden neurological deterioration
with obtundation or coma (widespread
meningoencephalitis ; alterations in CSF flow )
• multiloculated abscesses/ decreased distance
from the abscess capsule to the ventricular
wall/ deep-seated abscesses have been
correlated with increased risk
• localized ventricular enhancement on CT -
impending intraventricular rupture
• diffuse ependymal and meningeal
enhancement and the presence of debris within
the ventricles- IVROBA
• Hydrocephalus 50% & septation of the
ventricles delayed complication

22. Diagnostic Imaging and Laboratory Data
• CT cerebritis stage- poorly defined area of low attenuation with a mass effect and
significant edema
• capsule- peripheral enhancement increases and the center of the lesion becomes
progressively hypodense
• Corticosteroids- reduce the thickness of the abscess capsule and the extent of contrast
enhancement on both CT and MRI
• DwMRI -high degree of sp & sn in differentiating spontaneous abscess from other ring-
enhancing lesions/ presence of restricted diffusion;non-specific
• correlation with ADC & T2-w MRI sequences or CT is necessary to evaluate for blood
products that may cause a “T2 shine-through effect,” in which the infection appears
bright on diffusion-weighted images
• Peripheral leukocytosis is frequently absent, and although the ESR and CRP
concentration are usually elevated
• Blood cultures seldom yield a causative organism/LP c/i

23. Axial CE T1-w mri ;two rim-enhancing masses of
the left periventricular white matter that
represent abscesses. The intraventricular
enhancement is suggestive of ventriculitis.
Axial fluid-attenuated inversion recovery
(FLAIR) image of the same pt.- vasogenic
edema surrounding each lesion.

24. Purulent drainage developed after craniotomy for a left frontal cavernous
malformation
A.T1-w axial MRI after gadolinium administration demonstrates enhancement
within the extra-axial space and the resection cavity. A craniotomy with
drainage of purulent material from the epidural and subdural compartments
was performed, and treatment with intravenous antibiotics was started. Five
days later, severe headache and worsened mental status developed
B. MRI - IVROBA
One month after resection of a right frontal glioma, this patient exhibited confusion and lethargy.
T1-w axial MRI obtained before (A) and after (B) gadolinium administration demonstrate enhancement of the resection
cavity and surrounding meninges, and the fluid-attenuated inversion recovery (FLAIR) sequence (C) shows significant
surrounding edema. Abnormal restricted diffusion on DWMRI (D) suggests infection. Craniotomy confirmed the presence
of purulent material in the subdural and intraparenchymal locations

25. Treatment
• goals - to relieve the mass effect; improve clinical symptoms & fully resolve the
infection
• In most cases, a combination of sxl drainage (iopen operative drainage or excision of
the lesion and stereotactic aspiration ) & a prolonged course of iv antibiotics (6-8 wks
f/b oral)
• Progressive enlargement of the abscess or failure of the abscess to become smaller- sxl
• intraventricular administration of antibiotics, most commonly vancomycin,
aminoglycosides, and colistin
• Adjunctive corticosteroid - significant cerebral edema related to cerebral infections
with signs of impending herniation/ seizure prophylaxis until infection resolved

27.  Postoperative Infections of the Spine
• risks, symptoms & Rx depend on the region of the intervention (cervical, thoracic,
or lumbar), the approach (anterior, posterior, or lateral) & instrumentation
 Noninstrumented spinal surgery (anterior and posterior decompressive procedures)
;usually confined to short stretches of the spinal column; mostly single level
• Lumbar diskectomy < 1% (ssi or muscle tissue, or in the disk space)/ laminectomy
without fusion ~2%.
• Backache with fever; elevation in ESR/CRP; later - radiographic changes with disk
degeneration; progressive cases- end plate degeneration
• Risks: longer operating times (>5 hrs), greater blood loss( >1L), no. of levels,
greater soft tissue destruction,revision of sx, sx extending below sacrum, ≥2
resident surgeons, the placement of devascularized allograft, long hospital stay,
traumatic spinbal injury / pt. comorbidities-obesity/DM/malignancy-20%/
 Instrumented Spinal Procedures - posterior spinal procedures ~3% to 7%.
• type of instrumentation - older steel implants v s newer titanium implants
• Anterior instrumented spinal procedures -lower rates of infection
• anterior-posterior approach - highest rates of infection
• MIS- no reduction in wound infection
• intrathecal drug delivery systems and spinal cord stimulators ~5% ;within the first 2
weeks to 2 months after surgery& treated by removal of the complete system

28. • Superficial-above the lumbodorsal fascia in the dermis and s.c tiss.;manifest in the immediate
posto period with erythema, purulent drainage, local tenderness, and separation or dehiscence of
the wound edges
• low-grade fever; elevated ESR/CRP/WBC;variable
• Deep - more variable manifestation; most manifesting 2 to 3 weeks posto or after several months
to several years after surgery
• acute manifestation-significant pain, fever, anorexia, and night sweats
• wound overlying a deep infection-normal/track superfcially
• delayed manifestation progressive backache, wound drainage, and erythema but may lack fever
• serial ESR/CRP values with trends-useful in diagnosing and monitoring; tracking the response to
treatment
• If debridement is planned, specimens should be taken from both superficial and deep parts
• blood cultures may aid in the diagnosis of a pathogen
• CT- guided or open biopsy may be helpful; 30-50%

29. Sagittal CT of Pt. with discitis of L5-
S1;end plate sclerosis,VB collapse &
focal kyphosis.
MRIs of thoracic discitis; A.Sagittal T1-w NC MRI; B.Sagittal T1-w CE MRI; hypointense SI in VB &
avid enhancement ; C. Sagittal T2-w sequence MRI in a Pt. with postop L5-S1 discitis; hyperintense
signal in adjacent end plates
• Plain radiographs -assessment of spinal alignment, paravertebral soft tissue
swelling;bony changes; integrity of spinal hardware/MRI-ioc
• Early bone changes ~2 to 3 wks postop with evidence of disk space narrowing, bone
destruction & blurring of end plates f/b VB collapse or sclerosis of end plates and
bone ankylosis in the more chronic setting
• Increased soft tissue swelling, especially in the retropharyngeal space after anterior
spinal surgery- abscess
• lucency around screws - loosening, hardware failure, or pseudoarthrosis

30. Nonoperative Treatment :
• SSI, Postoperative discitis /Use of an external brace in postope discitis/iv antibiotics 6 wks f/b
oral 6 wks
Surgical treatment :
• Goals -(1) diagnosis of the infective agent (2) débridement of nonviable tissue, and (3) assurance
of stabilization
• Preop imaging-extent of debridement; evidence of deep infection mandates opening of the
lumbodorsal fascia
• Opened only after thorough debridement and irrigation of the superficial compartment
• Loose bone fragments, gel foam or fibrin sealant remnants, and necrotic muscle and fat should be
meticulously removed
• If instrumentation is found to be loose-an alternative means of fixation must be used
• In the case of pedicle screw fixation, a screw of larger diameter can be used as a “rescue screw.”
• Structural allograft tissue used in the initial construct may also be left in place, but loose chips of
bone should be removed
• Primary wound closure should be performed if possible
• The wound should be closed in layers around a drain to eliminate dead space
 Wound Vacuum-Assisted Closure
 Irrigation-Suction Technique
 Other Surgical Techniques : use of antibiotic beads and muscle flaps
 Vancomycin Powder

31. Use and Misuse of Antibiotics in Neurosurgery
• Antibiotics are an integral part of the daily life of the neurosurgeon
GENERAL PRINCIPLES OF ANTIBIOTIC USE
• Not only CNS but cranial soft tissues, skull, and paranasal sinuses; the spine, intervertebral
disks, and paraspinal soft tissues; and the tissues
• delivery not depend on physiology of either BBB/BCSFB; act as obstacles
• active influx and efflux transporters located on the endothelial/epithelial cell surface alter
the distribution of an antibiotic
• goal : to deliver an adequate concentration of the drug to the proper compartment
• Dose & choice of antibiotics/intraventricular drugs
Pharmacokinetics of Antibiotic Delivery
• Concentrations throughout CSF not constant (Ventricular < lumbar CSF)
• Penetration depend of stage of abscess (blood-abscess barrier)
• Most are not metabolized in the CSF/elimination by diffusion or CSF turnover
• Generally, CSF t1/2 of antibiotics >> plasma t1/2
• CSF t1/2 increased in CNS infections (decreased turnover)
• Pt. with CSF shunts or external CSF drains, CSF t1/2 the CSF quite (altered circulation)

32. CNS Toxicity of Antibiotic Therapy
• include encephalopathy, seizures, psychiatric symptoms, cranial nerve injury, and ataxia
• most commonly used intrathecal antibiotics, vancomycin and gentamicin- relatively low
toxicity
• Intraventricular vancomycin relatively free of toxicity, even at high CSF levels
• Intraventricular gentamicin may have CNS toxicity, causing ototoxicity or epilepsy
• Intraventricular administration of β-lactam similar to systemic ; seizures
• infection rates range < 1% in clean wounds to 6% to 10% in dirty wounds, even with
antibiotic treatment
• Clean shunt implantations utilizing antibiotic prophylaxis ~ 8-10% infection rate
• use of prophylactic antibiotics; irrigation of the wound and filling the shunt with
antibiotic solution and antibiotic-impregnated ventricular drains

33. • Judicious use and adherence to basic principles
• Basic principles :
1. Antibiotics only for the prevention or treatment of susceptible
infections
2. choice of antibiotic guided by the most likely pathogen and directed by
C/S results
3. used for their shortest effective duration
4. risks associated must be considered
5. Adequate Dose and frequency
• Failure -antibiotic misuse; ineffective(MDR) to harmful(superinfection)
• MC misuses of antibiotics in neurosurgery: Intraventricular administration
of chloramphenicol/ Routine use of vancomycin for prophylaxis
• appropriate consultation with specialists in infectious diseases

34. Meningitis and Encephalitis
• Meningitis is defined as inflammation of the meninges, the lining of the brain and spinal cord
• Encephalitis represents inflammation of the brain, and the pathogens typically responsible are quite
different from those usually seen in meningitis
• overlap between the two (meningoencephalitis)
• Ventriculitis is focal or diffuse inflammation of the ependymal lining of the cerebral ventricular system
• Community-Acquired Bacterial Meningitis;Streptococcus pneumoniae and Neisseria meningitidis
• 30-50% of survivors sustaining neurological sequelae
• 60% pneumococcal meningitis;triad consisting of fever, nuchal rigidity, and altered mental status
• mortality associated with pneumococcal meningitis 15-25% for pediatric & 20-37%
• Pneumococcal vaccines have been developed and proved to be very effective in the prevention of
invasive pneumococcal disease, including meningitis
• efficacy of the heptavalent pneumococcal conjugate vaccine ~97%

35. • uncommon after neurosurgical procedures; < 1%
• clinical course of nosocomial meningitis tends to be less fulminant than that of
community-acquired meningitis
• typical symptoms- fever, headache, and neck stiffness/non-specific; without
infection in posterior fossa sx/chemical irritation
• aseptic (chemical) meningitis 60%-75% of postop meningitis; frequently in
children and after posterior fossa surgery
• Others : craniopharyngiomas/ Rathke’s cleft cysts/ epidermoid & dermoid
cysts/ cholesteatomas
• Release of the irritating element; chronic headache syndrome relieved by
resection of the offending lesion
• Diagnosis of aseptic meningitis- negative CSF Gram staining & sterile culture
and full recovery without antibiotics
• Corticosteroids- symptomatic relief in aseptic chemical meningitis

36. Diagnostic Imaging and Laboratory Data
•no single clinical sign or diagnostic test
distinguishes between the two entities
•Neuroimaging studies rarely assist in the
diagnosis of postop meningitis b/c the
characteristic sign, meningeal enhancement
in 80% of postcraniotomy pt. without
infections
•CT or MRI -secondary complications of
meningitis;HCP, parameningeal abscess, and
ischemia/ infarction related to vasculitis and
thrombosis of superficial vessels
•CSF culture data remain the “gold standard”
•Newer diagnostic tests : CSF lactate/IL-1β-
promising data

37.  Neisseria meningitidis; young adults and children (after the neonatal period);sporadic, and endemic-
serogroups B, C, and Y
• Assost. with smoking & deficiencies in the complement system, specifically the terminal components C5-8
• Four clinical syndromes have been described in meningococcal disease:
(1) bacteremia without sepsis,
(2) meningococcemia without meningitis,
(3) meningitis with or without meningococcemia, and
(4) meningoencephalitis.
• classic meningitis triad- 27%
• Prototypical skin lesions (purpura and petechiae-hemorrahagic rash; HALLMARK) - 60% of adults & 60-90%
of children
• mortality 4-8% in children and 7% in adults, with septicemia the MCC
• 8-20% neurological sequelae;SNHL,MR,seizures
• Other : Waterhouse- Friderichsen syndrome (a massive hemorrhage into the adrenal glands)& DIC
• Current guidelines recommend the use of penicillin or ampicillin
• conjugate vaccine 11-55 yrs
• Asst. with a high risk of secondary infection in close contacts; rifampin 600 mg BD x 2 days; 20 mg/kg/day
for children

38.  Diagnosis
• Rapid diagnosis and treatment of bacterial meningitis are critical
• LP should be done before institution of antibiotic therapy
• Suspected increased ICP (h/o mass lesion, new-onset seizures, FND, papilledema, and
severe impairment of consciousness) – CT/MRI head before LP
• use a small-bore (25-gauge) needle
• Severe HCP- require a ventriculostomy
• CSF Gram stain-pathogen in 60-90%
• CSF culture “gold standard”; 80-90%
• CSF lactate >35 mg/dL; RDT with promising result Sn 93%/Sp 96% differentiating bacterial
meningitis from aseptic meningitis;limited by other conditions- stroke/trauma
• CRP >20 mg/L useful in discriminating bacterial from viral etiology
• Procalcitonin (PCT) > 0.5 ng/mL with Sn 99%/Sp 83% distinguishing bacterial from aseptic
meningitis
• Blood cultures routinely done;50-80%
• Others : PCR/ latex agglutination test (LAT)

39.  Radiologic Studies
• X-ray chest, skull & sinuses
• CT scans of the skull base - predisposing
conditions such as sinus infection, mastoiditis,
skull fractures & congenital anomalies
• MRI is superior to CT; leptomeningeal
enhancement and distention of subarachnoid
space
• diagnosis of meningitis is not based on imaging
findings but allow delineate complications like
HCP/abscess/subdural empyema or
effusion/infarct
• In straightforward cases of bacterial meningitis,
early CT and MRI- normal
• LP is still the most important diagnostic study
 Treatment
• Prompt clinical diagnosis of meningitis f/b rapid
administration of antibiotics is a key factor
• Delays- worse outcome.
• After collection of CSF, empirical antibiotic
therapy started ASAP

40.  Nosocomial bacterial meningitis
• 0.5% ;serious complication of neurosurgical procedures, systemic infection & TBI
• MC gram-negative rods (E. coli, Pseudomonas aeruginosa, Proteus mirabilis, Enterobacter,
Acinetobacter), Propionibacterium acnes, streptococci, and Staphylococcus aureus)
• prolonged hospital stays, multiple operations & increased morbidity
 Postcraniotomy meningitis
• 0.8-8.9% cranial surgery; MC S. aureus and Staphylococcus epidermidis; gram-negative
• CSF results are altered by the operation/anesthesia/use of steroids
• Risk: EVD/CSF leakage/periop steroids/incisional infection/male /operative time > 4 hrs.
• 1/3rd within 1 wk of surgery, 1/3rd in 2nd wk & 1/3rd after 2 wks.
• most powerful risk factor for postoperative CSF -early reoperation (within 1 month)
• prophylactic antibiotic therapy reduced the incidence of incisional infection from 8.8% to 4.6%
it didn’t prevent the development of meningitis

41.  EVD induced Meningitis/ ventriculitis; 8-23%
• risk : greater frequency of CSF sampling/ >11 days; mc gram-positive cocci
(S. aureus and S. epidermidis) consistent with skin flora
• Intrathecal antibiotics administered through the EVD may be desirable,
but this approach is not standardized
 Lumbar Drain induced Meningitis ~5%
 Posttraumatic Meningitis; 0.2-1.4% in moderate or severe head trauma
• closed head trauma;mostly asst.with basilar skull fracture and
subsequent CSF leakage
• CSF rhinorrhea and otorrhea significant independent risk factors
• Open (compound) cranial fractures ~5%
• Trauma guidelines recommend that skull fractures depressed deeper than
the thickness of the cranium be surgically debrided

42.  Recurrent bacterial meningitis : 2 separate episodes of meningitis separated by a
period of full recovery; 6%
• Risk : 1) anatomic factors (2) immunodeficiencies [(X-linked agammaglobulinemia
(Bruton’s disease),HIV]& (3) chronic parameningeal infections (sinusitis, otitis
media, and mastoiditis. )
• Anatomic factors -congenital (encephaloceles, congenital inner ear
dysplasia,)/acquired (head trauma or skull fracture-csf leak )
• head trauma MCC
• CT scan with thin cuts through the skull base on bone windows
 Encephalitis or meningoencephalitis: gram-negative bacillus Legionella
pneumophila/Mycoplasma pneumoniae/L. monocytogenes
• Aseptic meningitis - nonbacterial inflammation of the tissues lining the
brain;viruses/fungi/parasites/protozoa/Rickettsia species
• noninfectious etiologies (e.g., drugs, collagen vascular disorders, sarcoidosis)
• Viruses account for the vast majority of cases of aseptic meningitis
• any age but most common in infants and children.
• Enteroviruses are the most common cause of viral meningitis
• include echovirus, coxsackievirus groups A and B & poliovirus
• transmitted via the fecal-oral route

43. HSV : mcc of viral encephalitis; mainly HSV-1/HSV-2 4-6%
• age distribution is bimodal;6M-20yrs,>50 yrs
• primary infection (30%) or virus reactivation (70%)
• Pathologically, herpes encephalitis- an acute focal, necrotizing encephalitis
with inflammation and parenchymal swelling
• predilection for the temporal lobe and limbic system/ olfactory
hallucinations
• Mollaret’s meningitis, a syndrome with recurrent bouts (≥3) of fever & S/S
of aseptic meningitis, recovery is rapid & spontaneous; d/t an occult
reservoir of HSV-1/HSV-2
• EEG shows paroxysmal lateralized epileptiform discharges
• mortality ~ 80% in infants without treatment
• I.V Acyclovir x for 2 weeks; mortality reduced to 20%
• survivors -the risk of long-term neurological sequelae is 62%

44. • FLAIR MRI is most sensitive for showing areas of cerebral involvement and
resulting inflammatory changes.
• In this axial image, hyperintensity is visible in the right temporal lobe affecting
the uncus and insular cortex as well as the subfrontal cortex. Although not
present in this patient, foci of hemorrhage are common.
•microglial nodules and cytoplasmic and intranuclear inclusion bodies

45. Tuberculous Meningitis
• TBM begins with bacterial seeding of the brain with the
formation of tubercles- rupture and cause seeding to
adjacent subarachnoid space
• military tuberculosis/generalized tuberculosis with a
single area/any age (adult>children)
• usual location- basal meninges
• exudate obliterates the basal cisterns
• not confined to SAS only as in bacterial meningitis, but
instead spreads along pial vessels to invade adjacent
brain
• Headache 50%; stiff neck 75%, and
lethargy/confusion/fever are typical.
• chronicity leads to frequent cranial nerve
involvement;20% at time of admission;poor outcome
• glucose level, which is reduced but usually not to the very
low as in bacterial meningitis
• Currently the diagnostic of choice- PCR analysis
• MRI- HCP as well as CE within the basal cisterns, subpial
cortex, and subependymal areas/frank tuberculoma
• self-limited meningitis k/A serous meningitis
• meningeal signs are mild
Role of Dexamethasone in TB meningitis

46. Tuberculous meningitis
A.Axial T1-w: CE thick enhancement of the basal cistern (arrows), as
well as abnormal enhancement in Rt. occipital horn (asterisk)
B. sagittal T1-w CE: abnormal enhancement coating pituitary stalk
& brain stem, continuing caudally along S.C (arrows)
Tuberculoma;Pt. with seizure
Axial T2-w (A) & T1-w CE MRI (B)- single
ring-enhancing Rt. parietal lesion with
moderate edema

47. • Occasionally an intracerebral tuberculoma- resection if it has mass effect or
it fails to shrink with drug therapy
• Neurological impairment 20-30% of survivors
• Hyponatremia 49%/Hydrocephalus 42%/Stroke 33%/Cranial nerve palsies
29%/Epileptic seizures 28%
• Diabetes insipidus 6%/Tuberculoma 3%/Myeloradiculopathy 3%
/Hypothalamic syndrome 3%
• The single most effective drug is isoniazid;neuropathy and hepatitis in
alcoholics; Pyridoxine/Optic neuropathy- ethambutol; visual acuity & color
discrimination
• HRZS all enter CSF readily in the presence of meningeal inflammation
• Ethambutol is less effective unless used in high doses
• 2nd line drugs : Ethionamide, Cycloserine, Ofloxacin & PAS
• 4 Drugs for 2 months f/b 2 Drugs (7 to 10 months)

48. Anti-Epileptic Drug in TB Meningitis
•New onset seizures 50% of children & 5% of adults
•Acute Management – Short acting Benzodaizapines & Phenytoin
•Long Term Rx with Phenytoin, Valproate - Hepatotoxic as well as Enzyme inducer
•Levetericetam-Safely given
•Rx on lines of Symptomatic seizure disorder
•neuroimaging and EEG-If normal give for 2 year seizure free
•If tuberculoma or any other lesion present may be offered for longer period
Role of Osmotic Agents in TBM
•Short term use of Mannitol, Frusemide and Acetazolamide in Stage 1 & 2
Disease
•Manitol can be given upto 72 hrs
•Frusemide & Acetazolamide may be used for weeks
• Only in Open Hydrocephalus

49.  Cryptococcal Meningitis : MC;C.
neoformans (soil with bird feces)
• common opportunistic infection in HIV
• usually subacute/chronic
course;headache & malaise,altered
mental status 20%
• basilar meningitis, miliary
parenchymal nodules
• infiltrate brain via the perivascular
spaces
• dilation of perivascular spaces c/a
“gelatinous pseudocyst presentation”
• mortality of HIV-associated
cryptococcal meningitis 22-40%
despite Rx
Cryptococcosis
HIV Pt.; Axial T2-w (A) & T1-w CE (B)- single small,
enhancing lesion in left corona radiata with moderate
associated edema

50. Protozoa
 Toxoplasma gondii c/b obligate intracellular
parasite Toxoplasma gondii/MC in HIV/ ingestion
of contaminated cat feces/undercooked meat
• CF: rash/myocarditis/polymyositis;
meningoencephalitis (seizures/confusion/coma)
• Lesions are scattered throughout the brain, and
adjacent to the subarachnoid space cause the
meningitis component of the
meningoencephalitis
• Diagnosis can be achieved by finding organisms in
the CSF or in stereotactic biopsy specimens of
brain lesions.
• MRI :solid to ring enhancing lesions/combination;
/any location/single or multiple
• Positive response to medical Rx-diagnostic
 Rx: combination of pyrimethamine (100-200 mg
D1 f/b 50-75 mg/day x 6 wks) & sulfadiazine(4-6
g/day x 6 wks)- DOC
 Folinic acid/Leucovorin (10-25 mg/day) to
prevent pyrimethamine-induced hematologic
toxicity
HIV Pt. with seizures & CSF + for toxoplasma Ag; T2-w &
T1-w CE of cerebral hemispheres (A & B) ; ring-enhancing
lesion with an eccentric enhancing nodule

51. Acquired Immunodeficiency Syndrome
• affect CNS/PNS both directly & indirectly
• Direct infection CNS- acute retroviral syndrome/aseptic meningitis/transient & self-limited
• Chronic HIV infection: HIV-associated encephalopathy/ myelopathy/ increased risk of stroke
• highly active antiretroviral therapy (HAART)- robust immune response k/a the immune reconstitution
inflammatory syndrome (IRIS);affect CNS
• Toxoplasma/Cryptococcus/mycobacterial/viruses-JC virus & CMV/bacteria-Treponema & Bartonella
species
• CNS Lymphoma asst. with concomitant EBV infection
CNS lymphoma
A. coronal T1-w CE;solidly enhancing lesion infiltrating CC
B. axial T1-w CE ; faintly rim-enhancing lesion Rt. frontal lobe
immunocompetent - nonhemorrhagic, solidly enhancing lesion
immunosuppressed -ring-enhancing lesion with cystic or hemorrhagic components

52. HIV associated encephalopathy (HAE)
Coronal T2 w;ventricles & sulci
markedly prominent-significant volume
loss with minimal white matter signal
abnormality
Progressive multifocal leukoencephalopathy (PML)
HIV pt.; CSF-JC virus;
Axial T2-w: white matter signal abnormality involving Rt. frontal lobe & insula with spread across CC
to involve Lt. frontal lobe;involvement of subcortical U fibers (arrows) & nearly complete lack of
mass effect (classic)
Immune reconstitution inflammatory syndrome
(IRIS);HIV pt. on HAART
 Axial T2-w: very extensive, confluent signal
abnormality in the white matter of Lt. cerebral
hemisphere & lesser degree of Rt.Hemisphere
;similar to that of PML In this patient but more
mass effect

53. HELMINTHIC CNS INFECTIONS
 Cysticercosis; humans intermediate hosts of Taenia solium;
• neurocysticercosis (NCC);epilepsy-mc presentation; intracranial hypertension (obstructive HCP,mass
effect)/FND
• subacute course;difficult to differentiate NCC from neoplasia /other infections of CNS
• intense inflammation around cysticerci & diffuse cerebral edema- cysticercotic encephalitis ; severe form
of NCC
• spinal cysticercosis –motor & sensory deficits, vary a/c to level of lesion
• most typical imaging findings - cystic lesions showing the scolex & parenchymal brain calcifications
• Others: ring-enhancing lesions/abnormal enhancement of leptomeninges/HCP/cerebral infarctions
• CSF normal /CSF eosinophilia not consistent finding
• subarachnoid & ventricular forms -CSF analysis-lymphocytic pleocytosis/increased protein/ normal
glucose
• most accurate serologic test is immunoblotting (ELISA) /also for Rx response

54. Treatment
• cysticidal agents & corticosteroids with AED
• Albendazole 15 mg/kg/day x 1 wk & praziquantel 50 mg/kg/day x 2 wks- preffered regimen
• corticosteroids to prevent post-treatment seizure; routinely administered with cysticidal agents
• dexamethasone 8 mg/day for 28 days, started early during antiparasitic treatment for viable
parenchymal NCC
• Pt. with cysticercotic encephalitis should not receive cysticidal drugs; managed with high doses of
corticosteroids/osmotic diuretics/decompressive craniotomy if necessary
• giant subarachnoid cysticerci (>5 cm); cysticidal drugs with caution ; occlude small leptomeningeal
vessels ;stroke; concomitant steroid mandatory
• Patients with calcifications alone should not receive cysticidal drugs because these lesions represent
dead parasites
• Temporal lobectomy can be safely performed in patients with temporal lobe epilepsy with
hippocampal sclerosis caused by NCC without affecting cognitive outcomes and with a satisfactory
long-term seizure control provided selected patients remain on chronic antiseizure medication
• Hydrocephalus secondary to cysticercotic arachnoiditis requires placement of a ventricular shunt.
• Hydrocephalus may also be managed with endoscopic foraminotomy and endoscopic third
ventriculostomy

55. REFERENCES
1. Youmans and Winn Neurological Surgery; 7th edition
2. Ramamurthi & Tandon'S Textbook Of Neurosurgery; 3rd edition
3. Handbook of Neurosurgery. Mark S. Greenberg; 9th edition
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