Inflammations & infections Inflammations & infections of CNS of CNS

and Cerebrospinal fluidand Cerebrospinal fluid

Dr Aarathi RauDr Aarathi Rau

Infections of the CNSInfections of the CNSMeninges,brain,bothMeninges,brain,both Meningitis- Meningitis- Pachymeningitis:Epidural and subdural Pachymeningitis:Epidural and subdural

infections infections Leptomeningitis-Subarachnoid Leptomeningitis-Subarachnoid Brain-Brain- Cerebral abscess-focal inflammationCerebral abscess-focal inflammation Encephalitis-diffuse inflammationEncephalitis-diffuse inflammation

Formation,circulation,function of Formation,circulation,function of CSF CSF

Formation-500 ml/dayFormation-500 ml/day Ultrafilteration & secretion –choroid Ultrafilteration & secretion –choroid

plexus, ependymal lining of ventriclesplexus, ependymal lining of ventricles Circulation: ventricular system-foramina-Circulation: ventricular system-foramina-

subarachnoid spacesubarachnoid space

Function of CSFFunction of CSF Protects, lubricates the brainProtects, lubricates the brain Provides nutrients, removes wasteProvides nutrients, removes waste

90-150 ml adult90-150 ml adult

10-60 ml in newborn10-60 ml in newborn

Blood brain barrier –Blood brain barrier –homeostasis;electrolyteshomeostasis;electrolytes

Urea,glucose ,protein,creatinine passively Urea,glucose ,protein,creatinine passively along concentration gradient along concentration gradient

Normal CSFNormal CSF Thin, colourless, clear fluidThin, colourless, clear fluid Pressure 90-180mm WATER (10-100 neonates)Pressure 90-180mm WATER (10-100 neonates) 0-5 WBC’s /mm0-5 WBC’s /mm33 (neonates 0-30/ mm (neonates 0-30/ mm3 3 )) Lymphocytes & monocytesLymphocytes & monocytes Occasional ependymal or choroid plexus cellsOccasional ependymal or choroid plexus cells Protein 15-45mg/dlProtein 15-45mg/dl Glucose 50-80mg/dlGlucose 50-80mg/dl Chloride 113-130 mEq/LChloride 113-130 mEq/L SterileSterile

MeningitisMeningitisDef: inflammatory process of the Def: inflammatory process of the

leptomeninges & CSF within the leptomeninges & CSF within the subarachnoid spacesubarachnoid space

Meningoencephalitis =+inflammation of Meningoencephalitis =+inflammation of brain parenchymabrain parenchyma

ClassificationClassification AcuteAcute Aseptic Aseptic ChronicChronic

Pyogenic meningitis pathogenesisPyogenic meningitis pathogenesis Blood borneBlood borne Direct-sinuses,mastoid,middle ear,dural Direct-sinuses,mastoid,middle ear,dural

venous sinuses,direct trauma,fracture skullvenous sinuses,direct trauma,fracture skull Neonates:E Coli,Strep pneumoniae,Neonates:E Coli,Strep pneumoniae, Adolescents: N Meningitides, H influenzaeAdolescents: N Meningitides, H influenzae Adults: N Meningitides, Strep pneumoniae Adults: N Meningitides, Strep pneumoniae

type 3type 3 Elderly :Listeria monocytogenes,strep Elderly :Listeria monocytogenes,strep

pneumoniae type 3pneumoniae type 3

Clinical featuresClinical features

GeneralGeneral Headache,altered consciousness,vomitingHeadache,altered consciousness,vomiting Neck stiffnessNeck stiffness

GrossGross

Pus in the subarachnoid spacePus in the subarachnoid space Meningeal vessels engorgedMeningeal vessels engorged Location-Pneumococcal-convexitiesLocation-Pneumococcal-convexities Tracks along vessels, ventriculitisTracks along vessels, ventriculitis MicroscopyMicroscopy PMN in SA space,> meningial vesselsPMN in SA space,> meningial vessels Thrombosis of superficial vessels & Thrombosis of superficial vessels & Cerebral ischemic damageCerebral ischemic damage

CSF in Pyogenic MeningitisCSF in Pyogenic Meningitis

Increased pressureIncreased pressure Purulent/cloudyPurulent/cloudy ↑↑proteinprotein ↓ ↓ glucoseglucose Leucocytosis Leucocytosis Neutrophils ++Neutrophils ++ Gram stain Gram stain CultureCulture

SequeleSequele

ResolutionResolution Cerebritis,hemorrhagic infarction of brainCerebritis,hemorrhagic infarction of brain Fibrosing meningitisFibrosing meningitis HydrocephalusHydrocephalus Chronic adhesive arachnoiditisChronic adhesive arachnoiditis

(Aseptic)Lymphocytic meningitis(Aseptic)Lymphocytic meningitis

Viral usually (Viral usually (Coxsackie, EBV, ECHO)Coxsackie, EBV, ECHO)

Less fulminant than bacterialLess fulminant than bacterial Usually recoverUsually recover Few specimensFew specimens Mild lymphocytic infiltrate of the meningesMild lymphocytic infiltrate of the meninges

CSF in Viral meningitisCSF in Viral meningitis

Clear appearanceClear appearance

Mild pleocytosisMild pleocytosis

Lymphocytes +Lymphocytes +

ProteinProtein↑↑

Glucose –WNLGlucose –WNL

Culture sterileCulture sterile

Virological exam-Coxsackie, EBV, ECHOVirological exam-Coxsackie, EBV, ECHO

Tubercular meningitisTubercular meningitis Hematogenic spreadHematogenic spread Gross:Thickening & opacity of Gross:Thickening & opacity of

leptomenigesleptomeniges Basal meningitis, encasing cranial N’sBasal meningitis, encasing cranial N’s Discrete white granules on the meninges Discrete white granules on the meninges

+/-+/- Microscopy-granulomas, lympho-Microscopy-granulomas, lympho-

plasmacytic infiltrateplasmacytic infiltrate Obliterative endarteritisObliterative endarteritis

Tubercular meningitisTubercular meningitis

SequeleSequele-adhesive, fibrous, arachnoiditis,-adhesive, fibrous, arachnoiditis, HydrocephalusHydrocephalus Infarction following endarteritisInfarction following endarteritis Tuberculoma-intraparenchymalTuberculoma-intraparenchymal

CSF in Tubercular meningitisCSF in Tubercular meningitis

Moderate pleocytosisModerate pleocytosis Lymphocytosis (early –neutrophilia)Lymphocytosis (early –neutrophilia) Glucose Glucose ↓ (< pyogenic )↓ (< pyogenic ) Protein +++Protein +++ Cobweb appearance /clotCobweb appearance /clot AFB, culture, PCR.AFB, culture, PCR. Atypical mycobacteriaAtypical mycobacteria

SyphilisSyphilis

Meningovascular neurosyphilis:Chronic Meningovascular neurosyphilis:Chronic meningitismeningitis

Base of brainBase of brainCerebral convexities+/-,Cerebral convexities+/-,Spinal leptomeningesSpinal leptomeningesCerebral GummaCerebral GummaMicroscopy-endarteritis obliterans (Heubner Microscopy-endarteritis obliterans (Heubner

arteritis) with plasma cell cuffingarteritis) with plasma cell cuffing

Cerebral abscessCerebral abscess

Def: Focal inflammation of the Def: Focal inflammation of the parenchyma of the brainparenchyma of the brain

Routes of infectionRoutes of infection Secondary to meningitisSecondary to meningitis Local spread (middle ear,mastoid)Local spread (middle ear,mastoid) Hematogenous-BE,cyanotic heart Hematogenous-BE,cyanotic heart

disease,bronchiectasisdisease,bronchiectasis TraumaTrauma

GROSS MORPHOLOGYGROSS MORPHOLOGY Ill defined local Ill defined local

swelling swelling preferred sites frontal preferred sites frontal

lobe,parietal lobe lobe,parietal lobe cerebellumcerebellum

depending on aetiologydepending on aetiology C/S fibrous capsule C/S fibrous capsule

soft central soft central liquefactive necrosisliquefactive necrosis

surrounding oedemasurrounding oedema

MorphologyMorphology

MicroscopyMicroscopy Abscess containing necrosis surrounded Abscess containing necrosis surrounded

by granulation tissue ,fibrosis & gliosisby granulation tissue ,fibrosis & gliosis Microbiology:mixed bacteria + anaerobesMicrobiology:mixed bacteria + anaerobes

EncephalitisEncephalitis

Diffuse brain inflammationDiffuse brain inflammation Causative org: viral,rickettsia,bacteria Causative org: viral,rickettsia,bacteria

(listeria)(listeria) Death of neuronsDeath of neurons

HIV associated Neurologic HIV associated Neurologic disordersdisorders

Primary:Primary: CNS CNS Primary HIV encephalopathiesPrimary HIV encephalopathies Giant cell encephalitis, Giant cell encephalitis,

leucoencepalopathy, gray matter diseaseleucoencepalopathy, gray matter disease MyelopathyMyelopathy Lymphocytic Meningitis-seroconversionLymphocytic Meningitis-seroconversion PNSPNS Skeletal muscle myositisSkeletal muscle myositis

HIV associated Neurologic HIV associated Neurologic disordersdisorders

Associated with immune supressed Associated with immune supressed conditioncondition

Opportunistic infectionsOpportunistic infections LymphomaLymphoma

CSF in AIDSCSF in AIDS Aseptic HIV meningitis-lymphocytic Aseptic HIV meningitis-lymphocytic

meningitismeningitis Infections Infections M. tuberculosis less reactiveM. tuberculosis less reactive Mycobacterium avium intracellulareMycobacterium avium intracellulare CryptococciCryptococci NeurosyphilisNeurosyphilis MalignanciesMalignancies

OTHER INFECTIONSOTHER INFECTIONS

Prion disease (CJD)Prion disease (CJD) Fungal infectionsFungal infections Parasitic infections malaria, Parasitic infections malaria,

toxoplasmosis,Echinococcus,cysticercosistoxoplasmosis,Echinococcus,cysticercosis

Typical Cerebrospinal Fluid Findings in Various Types of

Meningitis

LowLow Usually normal

Normal to marked decrease

CSF-to-serum glucose ratio

ElevatedElevatedNormal to elevated

Mild to marked elevation

Protein

Predominance of lymphocytes

Predominance of lymphocytes

Predominance of lymphocytes

Predominance of PMNs

Cell differential

VariableVariable<100 per mm3>=1,000 per mm3

White blood cell count

VariableVariableUsually normal

ElevatedOpening pressure

TubercularFungalViralBacterialTest

Intracranial hemorrhageIntracranial hemorrhage

Intracerebral hematoma-associated withIntracerebral hematoma-associated with

hypertension,(AV malformations,tumour ) hypertension,(AV malformations,tumour ) Subarachnoid hemorrhageSubarachnoid hemorrhage Any age groupAny age group Associated with rupture of Berry aneurysmAssociated with rupture of Berry aneurysm

Hemorrhagic tapHemorrhagic tap

TraumaticTraumatic Clear supernatantClear supernatant

Clearing from tube 1 Clearing from tube 1 to 3to 3

Fresh RBC’sFresh RBC’s

Subarachnoid Subarachnoid hemorrhagehemorrhage

Xanthochromia>4 hrs Xanthochromia>4 hrs upto 2-4 weeksupto 2-4 weeks

Same appearance in Same appearance in 1,2 & 31,2 & 3

Crenated RBC’sCrenated RBC’s

Lumbar punctureLumbar puncture

DiagnosticDiagnostic Meningitis;bacterial,TB,fungal, viral Meningitis;bacterial,TB,fungal, viral **,syphilis ,syphilis encephalitis encephalitis Guillain Barre Syndrome Guillain Barre Syndrome Matastasis lymphoma,leukaemia,breast,lung Matastasis lymphoma,leukaemia,breast,lung HaemorrhageHaemorrhage Any disorder affecting the nervous system! Any disorder affecting the nervous system! TherapeuticTherapeutic Administer dye for imaging studies Administer dye for imaging studies Administer medications eg CT,anaesthesiaAdminister medications eg CT,anaesthesia

ProcessingProcessing

Method of collectionMethod of collection 3 sterile bottles3 sterile bottles Biochemistry & immunology-blood glucoseBiochemistry & immunology-blood glucose MicrobiologyMicrobiology Cell count,cytologyCell count,cytology Send QUICKLYSend QUICKLY