Csf and Infections Part One

8/13/2019 Csf and Infections Part One

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F E UN R M F Department of M E D I C I N E Section of N E U R O L O G Y

CEREBROSPINAL FLUID

SYSTEM


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CSF Description

A watery fluid that fills the ventricles andbathes the internal brain surface

Clear, colorless liquid containing smallamounts of CHON, glucose and potassium

There is no cellular component (up to 1-5

cells/mm3), high Na, Cl, and Mgconcentrations, and low glucoseconcentrations


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CSF Profile

PROFILE COMMON CAUSES

Purulent Bacterial

Lymphocytic, low

glucose

TB, fungal,

spirochetal,

sarcoidosis, CA

Lymphocytic, normalglucose

Viral


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CSF Description

The ventricles and subarachnoid space containapproximately 125 ml of CSF (25 ml in theventricles and 100 ml in the subarachnoid space)

70% - choroid plexus; 30% -capillary bed +

metabolic water production (capillary ultrafiltrate)

Net production: 0.35-0.37 ml per minute(400ml/day)

CSF turnover rate of 0.25% per minute


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CSF Function

It provides physical support and cushionfor the brain which floats within the liquid

It serves an excretory function andregulates the chemical environment of the

central nervous system

It acts as a channel for chemicalcommunication within the central nervoussystem


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CSF Function

Removes waste products of neuronalmetabolism, drugs and other substanceswhich diffuse into the brain from the blood

Integrates brain and peripheral endocrinefunctions (hormone-releasing factors)

Influences microenvironment of neuronsand glial cells (via pia-glial membrane)


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CSF Production

Total cerebrospinal fluid production isapproximately 500 ml per day (450-600ml/day)

70% of the CSF is produced by the choroid

plexus and the remaining 30% is derived frommetabolic water production

Of the 30%, 12% is produced by way ofoxidation, 18% is capillary ultrafiltrate

Net production in man is about 0.35 ml/min


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BACTERIAL INFECTIONS

Acute meningitis

Acute encephalitis

Subdural empyemaEpidural abscess

Intracranial septic thrombophlebitis

Brain abscessSubacute and chronic meningitis



BACTERIAL INFECTIONS OF THE

CENTRAL NERVOUS SYSTEM

Bacterial infections reach the intracranialstructures by :

Hematogenousspread (emboli of bacteriaor infected thrombi)

Extension from cranial structures (ears,

sinuses)

Iatrogenic



Bacterial Infections

Hematogenous spread:In most cases of bacteremia, the CNS seemsspared

Direct injection of virulent bacteria into the brainseldom results in abscess

Cranial epidural and subdural spaces are practicallynever the sites of blood-borne infections

In humans, infarction of brain tissue by arterial orvenous occlusion appears to be common andperhaps a necessary antecedent



Bacterial Infections

Extension from cranial structures Infected thrombi may form in the diploic veins and

spread along to the dural sinusesmeningealveinsbrain

An osteomyelitic focus may form with erosion ofthe inner table of the skull and invasion of the dura,subdural space, pia-arachnoid layer and brain



Etiology:

Most common organisms in adults:Streptococcus pneumoniae, Neisseria meningitidis,H. influenzae, Listeria monocytogenes

Most common organisms in neonates:

E. coli, Group B Streptococcus

Most common organism in children:

H. influenzaecontrolled

When septic embolus comes from lungs, congenitalheart lesions, ears and sinuses: Mixed flora

Iatrogenic infections: Staphylococcal



Which is the normal brain?



Normal Meninges Meningitis


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ACUTE BACTERIAL MENINGITIS


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Acute Bacterial Meningitis

Inflammatory reaction in the pia, arachnoid andthe CSFof the brain and spinal cord

Initial hyperemia and permeability of vessels exudation of protein and migration ofneutrophils.

Neutrophils disintegrate replaced by

lymphocytes, histiocytes and plasma cells

Cellular exudate forms and organizes resulting infibrosis of the arachnoid and loculation of pocketsof exudates


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N. meningi t id is

Intracellular Gram(-) diplococci

H. inf luen zae

Gram (-) bacilli

S. pneumoniae

Gram (+) diplococci

Staphylococcus

Gram (+) cocci


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Pathogenesis

The most common pathogens are allnormal flora of the nasopharynx and dependon their antiphagocytic capsules for survival

Postulated factors that predispose todisruption of the blood-CSF barrier and invasionof the bloodstream and meninges include:

Precedent viral infection

Trauma

Endotoxins


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Clinical Features

Adults and children

Fever, severe headaches, stiff neck, sometimeswith generalized convulsions and alteredsensorium

Nuchal rigidity, Kernig and Brudzinski signs

1. Meningococcal

Extremely rapid evolution (hours), petechial andlarge ecchymoses, circulatory shock, epidemicsetting


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Meningococcal rash


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2. Pneumococcal

Follows infection of lung, ears, sinuses, heartvalves

Alcoholics, splenectomized, very elderly, sickle

cell disease, recurrent bacterial meningitis

3. H. influenzae

Follows ears and URT infections in childrenEarly focal cerebral signs


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4. Staphylococcal

Follows neurosurgical procedures, furunculosis,ventricular shunts

5. Enterobacteriaceae, Pseudomonas,Listeria,Acinetobacter calcoaceticus

Immunosuppressed


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Clinical Features:

Infants and Newborns

Fever, irritability, drowsiness, vomiting,convulsions and bulging fontanel

More common in males (3:1)

Maternal infection is the most significant factor


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CSF Examination

INDISPENSABLE part of the examination ofpatients suspected with meningitis

Elevated pressure

Pleocytosis 250-100,000/mmNeutrophils predominate (85-95%)

Protein is higher than 45mg/dl

Glucose is usually 40mg/dl or 40% of RBSGram stain and cultures

High LDH particularly fractions 4 and 5


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Other tests

Blood culture

Chest x-ray

Serum Na - SIADH

CT scanlesions that erode the skull or spine,brain abscess, empyema

MRI with gadoliniummeningeal exudate and

cortical reaction, venous occlusions andadjacent infarctions


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Acute bacterial meningitis

This contrast-enhanced, axial

T1-weighted magneticresonance image showsleptomeningeal enhancement.


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Empiric treatmentAge of patient Antimicrobial therapy

0-4 weeks Cefotaxime +ampicillin

4-12 weeks 3rdgen cephalosporin +

ampicillin

3 mo18 yrs 3rdgen cephalosporin +

Vancomycin

18-50 yrs 3rdgen cephalosporin +

Vancomycin

> 50 yrs 3rdgen cephalosporin +

Vancomycin + ampicillin

Immunocompromised Vanco + ampi + ceftazidimeBasilar skull fracture 3rdgen cephalosporin +

Vancomycin

Head trauma, Neurosurgery,

CSF shunt

Vancomycin + ceftazidime


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Prophylaxis

All household contacts of patients withmeningococcal meningitis

Highest for those younger than 5yrs old, 2-4%

Single dose of ciprofloxacin

Rifampicin 600mg every 12hrs for 2 days

Vaccination vs. H. influenza, N. meningitidis


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Prognosis and Sequelae

Untreated, usually fatalMortality rate:

Uncomplicated meningococcal and H. influenzae,5%

Streptococcal, 15%

Highest in the neonates, elderly, fulminantmeningococcemia, with concomittant alcoholism,DM, MM, head trauma, Osler triad

Mechanism of death:

Bacteremia and hypotension, brain swelling,aspiration pneumonia


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Prognosis and sequelae

Residual neurologic deficits are found in25% of H. influenzae, and 30% withpneumococcal meningitis

Cranial nerve palsies tend to resolve after afew weeks or months

Only half with deafness resolves

Hydrocephalus


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BACTERIAL ENCEPHALITIS


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Subdural empyema

An intracranial suppurative process between theinner surface of the dura and the subarachnoid

Usually originates from the frontal or ethmoidsinuses, less frequently from the sphenoid and

middle ear

Most common in adolescent and young adult men

Streptococci (nonhemolytic and viridans) are most

frequent followed by Bacteroides and anaerobicstreptococci


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SUBDURAL EMPYEMA


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Symptoms and signs: local pain andtenderness related to the origin of the infection

and its intracranial extension

Chills, fever, severe headaches, stiff neck,sensorial change, focal seizures, neurologic

deficits

Intracranial hypertension and papilledema

Diagnosis: should be considered whenever a

patient with a suppurative process in thesinuses or other cranial structures, developsmeningeal symptoms or focal neurologic signs


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CT scan: may show mastoiditis or osteomyelitisand crescent shaped area of hypodensity in

subdural space

MRI:more dependable visualization

CSF examination is not helpful and may be

dangerous

Treatment: most would require drainagecoupled with antibiotic therapy

Untreateddeath within 6 days

Treatedmortality rate 25-40% because oflate diagnosis


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Subdural empyemaand arterial infarct ina patient withbacterial meningitis.

Mass effect


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Empyema

from Otitis


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EPIDURAL ABSCESS


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Almost invariably associated with osteomyelitisin a cranial bone

Pus accumulate on the outer surface of thedura

Localizing neurologic signs are usually absent

LP is not advisable

Usually due to Staphylococcus aureus

AntibioticsSurgical drainage


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Infection involving the dural sinuses, the onesusually involved are the lateral, cavernous and

petrous sinusesExtension from the middle ear, mastoid cells,paranasal sinuses and skin around the upper

lip, nose and eyesStreptococci and staphylococci

Fever, intracranial hypertension, cranial nervepalsies and gaze abnormalities

Prolonged antibiotic treatment is the mainstayof treatment


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The MRI demonstratesleft cavernous sinusenlargement,decreased caliber of theleft internal carotid

artery, sphenoid andethmoid sinusitis,posterior fossaempyema, and

suppuration of the leftinternal auditory canal.


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BRAIN ABSCESS


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Encapsulated or free pus in the substanceof the brain

40% come from infection of the middle ear,mastoid cells, and PNS

50% hematogenous from heart and lungs20% source cannot be ascertained


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Etiology

Virulent streptococci, anaerobic andmicroaerophilicmost common (lungs andsinuses)

In combination with other anaerobes like

Bacteroides, Propionibacterium

E. coli, ProteusEnterobacteriaceae (ears)

Staphylococci

The type of organism depend on the source ofabscess


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Pathology

Septic thrombosis of vessels tissue necrosis local suppurative process

Within several days, the infection becomedelimited and the center of the infection takes on

the character of pus

As the abscess becomes more chronic, theperiphery grows granulation tissue and later on,

collagenous connective tissue ->capsuleThe capsule is thinner on the ventricular side


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Clinical manifestations

Headaches is the most frequent initial symptomDrowsiness and confusion, focal or generalizedseizures, focal neurologic deficits

Fever and leukocytosis are not consistently presentespecially during the encapsulated stage of theabscess

The symptoms may evolve in a treacherous and

unpredictable course even if the patient seemsstable because of rupture of the abscess!


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Treatment

During the stage of cerebritis and early abscessformation:

Antibiotics: Pen G or third gen cephalosporin AND

either chloramphenicol or metronidazole

for staphylococcal infection: Nafcillin or vancomycin

If the abscess is solitary, superficial andencapsulated or associated with a foreign body,should total excision be attempted

If abscess is deep, stereotactic aspiration is thecurrent method of choice.


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Prognosis

If the treatment is started while the patientis alert, mortality is at 5-10%

If the patient is comatose before treatment,

mortality is more than 50%

30% of survivors have neurologic residua,i.e., focal deficits or epilepsy


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Subacute and Chronic Meningitis

Induce an inflammation of the meninges oflesser intensity and chronicity

The organisms are more difficult to detect

and cultureTB meningitis

Neurosyphilis


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Tuberculous meningitis

Caused by the acid-fast Mycobacteriumtuberculosisand exceptionally by M. bovis andM. fortuitum

There has been a steady decrease in the casesof TB since WW II, but since 1985, there hasbeen a moderate increase again mainly, butnot exclusively, because of HIV epidemic


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Pathogenesis

First, a bacterial seeding of the meninges andsubpial regions of the brain and formation oftubercles

Followed by the rupture of one or more ofthese tubercles and discharge of bacteria intothe subarachnoid space


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Pathologic findings

Meningitis is most intense in the basal meningesUnlike the typical bacterial meningitis, the diseaseis not confined to the subarachnoid space andinvades the underlying brain (meningoencephalitis)

Cranial nerves are frequently involved


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Pathologic findings

Arteries become inflamed and occluded leading toinfarctions

Hydrocephalus forms because of blockage ofbasal cisterns

Multiple spinal radiculopathies and cordcompression occurs if the exudate predominatearound the spinal cord


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Exudates are seen atthe base of the brain(cranial nerves and

major arteries, circleof Willis)


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Clinical Features

Occurs in persons of all agesInitially, low grade fever, malaise, headaches,lethargy, confusion, and stiff neck with Kernig andBrudzinski signs

In the chronic stage, cranial nerve palsies,papilledema, FND because of infarction.

2/3 have evidence of active tuberculosis elsewhere

If untreated, it is usually fatal within 4-8 weeks ofthe onset


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Diagnosis

CSF:Slightly cloudy or ground-glass appearance withformation of a clot on standing

WBC 25-500 per cu. mm with lymphocytic

predominanceSugar 20-40mg/dl

Increased protein

(+) AFB smear in 20-30%

(+) TB-PCR

(-) serology for Cryptococcus and Syphilis


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CT or MRI may show enhancing exudates,hydrocephalus, areas of infarction andtuberculomas


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Tuberculoma behaving asan expanding mass lesion


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Basal exudates in TB meningitiswith concommitant

hydrocephalus


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Treatment

Quadruple anti-TB for 2 months (INH, RIF, PZA,ETH) then followed by 16-22 months of at leastdouble anti-TB antibiotics (INH, RIF).

Philippineshigh rates of INH-resistant organisms

Corticosteroids, in conjunction with anti-TB drugs,may be used who have subarachnoid block orraised intracranial pressure

Tuberculomas that do not disappear withmedication may be excised if there is a mass effect


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Prognosis

Overall mortality is still significant at 10%,infants and the elderly being at greatest risk

HIV positive patients have higher mortality

21%When coma has supervened before treatment,mortality is at 50%

20-30% of survivors have residual neurologicsequelae


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Neurosyphilis

Caused by a slender, spiral, motile Treponemapallidum

The treponeme invades the CNS within 3-18months of inoculation

The initial event is a meningitis which occurs in25%. The meningitis can be asymptomatic andcan only be discovered by LP!

Asymptomatic neurosyphilis is the most importantform because treatment at this stage can preventfurther symptomatic varieties.


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Principal Types

Asymptomaticabnormal CSF

Meningovascularmeningitis and strokes

Parenchymatous

Tabeticpain, paresthesia, ataxia caused by

posterior spinal root and dorsal column changesPareticpersonality changes, convulsions,dementia (dementia paralytica)

Optic atrophyvision loss and pallor of optic discs

Spinal- chronic fibrosing myelitis or meningovascularcomplications

Nerve deafness and vestibulopathy


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Diagnosis and Treatment

Syndrome consistent with neurosyphilisAbnormal blood titer of a treponemal antibodytest

(+) nontreponemal antibody test in CSF

Treatmenthigh dose IV penicillin 18-24M Ufor 14 days

All forms of neurosyphilis should be reexamined

every 3-4 months; CSF examination after 6months


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Other spirochetal infections

Lymes disease caused by Borrelia burgdoferi

from tick bitesErythema chronicum migrans

Acute radicular pain followed by chronic lymphocyticmeningitis and frequently with peripheral and

cranial neuropathiesHeart and articular surfaces are also affected


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Other spirochetal infections

Leptospirosiscaused by Leptospirainterrogans

rare cause of encephalitis, myelitis, opticneuritis, neuritis


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CASE

19 year old female, college student, with 1-week history of fever and headaches.

With history of acne vulgaris over the foreheadand above the bridge of the nose

Pertinent VS: tempt 39 C

Pertinent neurologic exam: drowsy, uttersincomprehensible words, spontaneously moves

all extremities equally; Bilateral Babinski sign;(+) nuchal rigidity


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Thank you for listening.

Maria Grace Ang-De Guzman, MD

Regina Victoria Reyes, MDGreg David Dayrit, MD

Maricar Yumul, MD

Robert Barja, MD

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Csf and Infections Part One