Acute CNS infection
• What is it?
• What causes it?
• What happens in the system?
• How to recognize it?
• How to prove it?
• How to treat it?
• How to prevent?
Significance
• Significant morbidity & mortality in children [1.2m cases worldwide]
• Diagnosis, challenging in young children
• High incidence of sequalae
• Fever with altered sensorium
• Virus > bacteria > fungi & parasite
• Meningitis
• Meningoencephalitis
• Brain abscess
• Common symptoms
photophobia, neckpain/rigidity, fits, stupor
• Diagnosis by CSF
Pyogenic meningitis
Etiology
• < 2months• Maternal flora, NICU/PNW flora;
• GBS, GDS, gram-ve, listeria, HIB,
• 2m-12m• Pneumococci, meningococci, HIB[now less]
• Pseudomonos, staph.aureus, CONS.
Reasons for infection
• Less immunity
• Contact with people with invasive disease
• Occult bacteremia [infants]
• Immunodeficiency
• Splenic dysfunction
• CSF leak , Meningomyelocele
• CSF shunt infection
Risk of infection
• Pneumococci OM, sinusitis, pneumonia, CSF rhinorrhea.
• Meningococci contact with adults, nasopharyngeal carriage
• HIBContact in daycare center
Pathogenesis
• Colonisation of nasopharynx
• Prior/concurrent viral URTI
• Bacteremia
• Hematogenous dissemination
• Contiguous spread from sinus, otitis, orbit
vertebral trauma, meningocele.
Why few only get meningitis?
• Defective opsonic phagocytosis– Developmental defects– Absent preformed anticapsular antibodies– Deficient complement/properdin system– Splenic dysfunction
Pathogenesis • Bacteria enter through choroid plexus of
LV
• Circulate to extra cerebral CSF & subarachnoid space
• Rapidly multiply in CSF
• Release of inflammatory mediators
• Neutrophilic infiltrates
• Increase vascular permeability
• Altered BBB
• Vascular thrombosis
Pathology
• Thick exudate covering all areas
• Ventriculitis, arteritis, thrombosis
• Vascular occlusion, sinus occlusion.
• Cortical necrosis, cerebral infarct
• Subarachnoid hemorrhage
• Hydrocephalus
• ICT, inflammation of spinal nerves
Clinical features • Nonspecific
– Fever,anorexia,myalgia,arthralgia,headache,– Purpura , petechiae, rash, photophobia.
• Meningeal signs– Neck rigidity, backache.– Kernig sign
– Brudzinski sign– Crossed leg sign
ICT signs
Headache, vomiting, drowsy, Fits Ptosis, squint, AF bulge, widened sutures Hypertension, bradycardia Stupor, coma Abnormal posturing Papilloedema [only in chronic ICT]
• Focal neurological deficit
• Cranial neuropathy– 3rd nerve– 6th nerve– 7th nerve– 8th nerve
Diagnosis
• LP & CSF analysis– Gram stain– Culture– Cell count– Glucose, protein
– [Contraindications for LP]
• Blood culture
CSF analysis• Cell count
– Normal• NB >30/mm3
• Child >5/mm3
– Meningitis >1000/mm3• Turbid 200-400/mm3• Early; lymphocytic predominance• Later; neutrophilic predominance
• low in severe sepsis
CSF analysis in prior antibiotic therapy
• Culture, gramstain altered
• Pleocytosis, protein, glucose unaltered
Traumatic LP
• Cell count, protein level altered
• Glucose, bacteriology unaltered.
Condition Pressure mm-h2o
Cell count/mm3 Glucose mg/dl
Protein mg/dl
microbiology
Normal 50-80 <5,lymphocyte >50, 75% of blood level
20-40mg
Bacterial meningitis
100-300 100-1000, >75% neutrophils
<40mg 100-500 Gram stain+ve
Partially treated meningitis
N / elevated
5-1000,Lymphocytes?
N /decreased 100-500 Gramstain ,c/s maybe -veAntigens +ve
Viral meningitis
Normal Less cells,lymphocytes
N, less in mumps
<200
TBM More <500,lymphocytes
<40 100-3000 Stain –veCulture ± ve
Fungal More 5-500 N More? Culture
Treatment • Rapidly progressive [ ~24h]
LP antibiotics
ICT , FND CTbrain & antibiotics
Manage shock, ARDS
• Subacute course [4-7d]
• Assess for ICT, FND
• Antibiotics CT LP
Supportive care• Monitoring
– Vitals– BUN,electrolytes,HCO3,IO, CBC,Platelets,Ca– Periodic neurologic assessment
• PR,sensorium,power,cranial N ex, head circ,
• Supportive care– IVF restrict for ICT,SIADH, more for shock – ICT ETI & ventilation,frusemide,mannitol– Seizures diazepam,phenytoin
Antibiotic therapy• Vancomycin & cefataxime/ceftrioxone
– Pneumococci,meningococci,HIB.
• Ampicillin / cotrimaxazole I.V– Listeria
• Ceftazidime & aminoglycoside– Immunocompromised
Duration of therapy
Pneumococci : 7-10 days Menigococci: 5-7 days HIB; 7-10 days E.coli,Pseudomonos ; 3 weeks Antibiotics started before LP [partially
treated meningitis] ; ceftrioxone 7-10 days.
Repeat LP
• After 48h
• For ; resistant pneumococci, gram-ve meningitis
Corticosteroids
• Rapid bacterial killing
• Cell lysis
• Release of inflammatory mediators
• Edema
• Neutrophilic infiltration
• 1-2h before antibiotics
• Dexamathasone q6h for 2 days.
• Less fever, less deafness.
Complications • ICT, Herniation
• Fits, Cranial N palsy
• Dural Vein sinus thrombosis
• Subdural effusion
• SIADH
• Pericarditis, Arthritis
• Anemia, DIC
Prognosis
• Mortality >10% [more in pneumococci]
• Prognosis poor in– Infants– Fits >4days– Coma, FND on presentation
• Neurological sequalae 20%– Behavior changes 50%– Deafness [pneumo,HIB], visual loss– MR,fits,
Prevention
• Meningococci– Rifampacin for close contacts [10mg/kg/day q12h for
2days]
– Quadrivalent vaccine for high risk children
• HIB– Rifampacin for contacts for 4days
– Conjugate vaccine
• Pneumococci – Heptavalent conjugate vaccine
TBM
• Subacute / ?chronic meningitis
• From lymphohematogenous dissemination
• Caseous lesion in cortex / meninges
• Discharge of TB bacilli in CSF
• Thick exudate infiltrate blood vessels
• Inflammation,obstruction,infarct.
• Brainstem affected
• Cranial N dysfunction
• Hydrocephalus
• Infarcts
• Cerebral edema
• SIADH
• Dyselectrolytemia
Features
• 6m-4yrs
• 3 stages
• Prodrome stage; 1-2 wks, nonspecific symptoms, stagnant development
• Abrupt stage;lethargy,fits,meningeal signs focal ND,cranial neuropathy,hydrocephalus.
Encephalitic picture
• Coma stage; posturing,hemi/paraplegia,poor vital signs
Diagnosis • Contact with adult TB
• Mx nonreactive 50%
• CSF – lymphocytes
• Glucose <40mg/dl
• Protein high: 400-5000mg/dl
• AFB +ve 30%
Thank you
Meningoencephalitis
• Encephalitis
• Encephalopathy
• Meningitis
• Myelitis
• Radiculitis
Meningoencephalitis
• Acute inflammation of meninges & brain tissue
• CSF – pleocytosis
• Gram stain & culture negative
• Mostly self limiting
Etiology
• Enterovirus
• Arbovirus
• Herpes virus
Pathogenesis • Direct invasion & destruction by virus• Host reaction to viral antigens• Meningeal congestion• Mononuclear infiltration• Neuronal disruption• Neuronophagia• Demyelination
Structures affected
• HSV; temporal lobe
• Arbovirus; entire brain
• Rabies; basal parts
Clinical features• Depends on parenchymal involvement• Preceding mild febrile illness & exantheme• Acute onset of high fever, headache,
irritability,lethargy,nausea,myalgia• Convulsions,stupor,coma• Fluctuating FND,emotional outburst
• Ant.horn cell injuryflaccid paralysis [west nile,entero virus]
DD
• Meningitis of various organisms
Diagnosis • CSF: lymphocytic predominance
– Protein: normal,high in HSV– Glucose: normal,low in mumps– Culture of organism [entero V]– Viral antigen by PCR
– Culture from NPswab,feces,urine• EEG: focal seizures [temporal];HSV• CT/MRI: swollen brain parenchyma
EEG patterns include focal slowing, spiking, and paroxysmal lateralizing epileptiform discharges.13 Focal-temporal or
lateralized polymorphic delta activity is the earliest change. Diffuse slowing soon follows, with a persistence of temporal predominance. Pseudoperiodic complexes, present on serial
EEGs in two-thirds of biopsy-proven cases, appear over temporal regions
MRI brain (T2W image): right temporal lobe high signal in a patient with herpes encephalitis
Treatment
• Acyclovir for HSV
• Non aspirin analgesic
• Nursing in a quiet room