CEREBROSPINAL FLUID SYSTEM

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

CSF Description
A watery fluid that fills the ventricles and bathes the internal brain surface
Clear, colorless liquid containing small amounts of CHON, glucose and potassium There is no cellular component (up to 1-5 cells/mm3), high Na, Cl, and Mg concentrations, and low glucose concentrations
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

CSF Profile
PROFILE Purulent COMMON CAUSES Bacterial

Lymphocytic, low glucose

Lymphocytic, normal glucose

TB, fungal, spirochetal, sarcoidosis, CA Viral

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

CSF Description
The ventricles and subarachnoid space contain approximately 125 ml of CSF (25 ml in the ventricles 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

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

CSF Function
It provides physical support and cushion

for the brain which floats within the liquid

It serves an excretory function and regulates the chemical environment of the central nervous system It acts as a channel for chemical communication within the central nervous system
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

CSF Function
Removes waste products of neuronal

metabolism, drugs and other substances which diffuse into the brain from the blood
Integrates brain and peripheral endocrine functions (hormone-releasing factors) Influences microenvironment of neurons and glial cells (via pia-glial membrane)

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

CSF Production
Total cerebrospinal fluid production is approximately 500 ml per day (450-600ml/day) 70% of the CSF is produced by the choroid plexus and the remaining 30% is derived from metabolic water production Of the 30%, 12% is produced by way of oxidation, 18% is capillary ultrafiltrate Net production in man is about 0.35 ml/min

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

INFECTIONS OF THE NERVOUS SYSTEM

CHAPTER 32
BACTERIAL Acute, subacute and chronic
FEUNRMF MEDICINE NEUROLOGY

Department of

Section of

BACTERIAL INFECTIONS
Acute meningitis
Acute encephalitis Subdural empyema Epidural abscess Intracranial septic thrombophlebitis

Brain abscess
Subacute and chronic meningitis

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

BACTERIAL INFECTIONS OF THE CENTRAL NERVOUS SYSTEM

Bacterial infections reach the intracranial structures by :
Hematogenous spread (emboli of bacteria

or infected thrombi) sinuses)

Extension from cranial structures (ears,

Iatrogenic
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Bacterial Infections
Hematogenous spread:
In most cases of bacteremia, the CNS seems spared
Direct injection of virulent bacteria into the brain seldom results in abscess Cranial epidural and subdural spaces are practically never the sites of blood-borne infections In humans, infarction of brain tissue by arterial or venous occlusion appears to be common and perhaps a necessary antecedent
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Bacterial Infections
Extension from cranial structures
Infected thrombi may form in the diploic veins and spread along to the dural sinuses meningeal veins brain

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

MEDICINE

Section of

NEUROLOGY

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. influenzae controlled

When septic embolus comes from lungs, congenital

heart lesions, ears and sinuses: Mixed flora

Iatrogenic infections: Staphylococcal

FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Which is the normal brain?

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Normal Meninges

Meningitis

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

ACUTE BACTERIAL MENINGITIS

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Acute Bacterial Meningitis

Inflammatory reaction in the pia, arachnoid and
the CSF of the brain and spinal cord

Initial hyperemia and permeability of vessels

exudation of protein and migration of neutrophils.

Neutrophils disintegrate replaced by

lymphocytes, histiocytes and plasma cells Cellular exudate forms and organizes resulting in fibrosis of the arachnoid and loculation of pockets of exudates

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Epidemiology
75% of sporadic cases worldwide are due to:

H. influenzae, Streptococcus pneumoniae, N. meningitidis

Predominating slightly in males 3:1

4th most common is L. monocytogenes H. influenzae getting less common in infants and
children and getting more frequent in adults Meningococcal more common in children and adolescents; low incidence after age of 50 Pneumococcal predominates in the very young and the old
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

N. meningitidis Intracellular Gram(-) diplococci

H. influenzae Gram (-) bacilli

S. pneumoniae Gram (+) diplococci

Staphylococcus Gram (+) cocci

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Pathogenesis
The most common pathogens are all normal flora of the nasopharynx and depend on their antiphagocytic capsules for survival Postulated factors that predispose to disruption of the blood-CSF barrier and invasion of the bloodstream and meninges include:
Precedent viral infection Trauma Endotoxins
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Clinical Features
Adults and children
Fever, severe headaches, stiff neck, sometimes with generalized convulsions and altered sensorium Nuchal rigidity, Kernig and Brudzinski signs

1. Meningococcal
Extremely rapid evolution (hours), petechial and large ecchymoses, circulatory shock, epidemic setting
FEUNRMF MEDICINE NEUROLOGY

Department of

Section of

Meningococcal rash
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

2. Pneumococcal
Follows infection of lung, ears, sinuses, heart valves Alcoholics, splenectomized, very elderly, sickle cell disease, recurrent bacterial meningitis

3. H. influenzae
Follows ears and URT infections in children Early focal cerebral signs

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

4. Staphylococcal
Follows neurosurgical procedures, furunculosis, ventricular shunts

5. Enterobacteriaceae, Pseudomonas, Listeria, Acinetobacter calcoaceticus

Immunosuppressed

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

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

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

CSF Examination
INDISPENSABLE part of the examination of patients suspected with meningitis Elevated pressure Pleocytosis 250-100,000/mm Neutrophils predominate (85-95%) Protein is higher than 45mg/dl Glucose is usually 40mg/dl or 40% of RBS Gram stain and cultures High LDH particularly fractions 4 and 5
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Other tests
Blood culture
Chest x-ray Serum Na - SIADH CT scan lesions that erode the skull or spine, brain abscess, empyema MRI with gadolinium meningeal exudate and cortical reaction, venous occlusions and adjacent infarctions

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Acute bacterial meningitis

This contrast-enhanced, axial T1-weighted magnetic resonance image shows leptomeningeal enhancement .

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Treatment
Medical emergency Sustain blood pressure and treat septic shock Choose an antibiotic that is bactericidal and can penetrate the CSF in effective amounts Antibiotics for 10-14 days except when there is persistent parameningeal focus, preferably intravenously Corticosteroids: before antibiotics
In chilren- dexamethasone 0.15mg/kg QID X 4days In adults- only in pneumococcal
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Empiric treatment
Age of patient 0-4 weeks 4-12 weeks 3 mo 18 yrs 18-50 yrs > 50 yrs Immunocompromised Basilar skull fracture Head trauma, Neurosurgery, CSF shunt Antimicrobial therapy Cefotaxime +ampicillin 3rd gen cephalosporin + ampicillin 3rd gen cephalosporin + Vancomycin 3rd gen cephalosporin + Vancomycin 3rd gen cephalosporin + Vancomycin + ampicillin Vanco + ampi + ceftazidime 3rd gen cephalosporin + Vancomycin Vancomycin + ceftazidime

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Prophylaxis
All household contacts of patients with meningococcal 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

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Prognosis and Sequelae

Untreated, usually fatal Mortality rate:
Uncomplicated meningococcal and H. influenzae, 5% Streptococcal, 15% Highest in the neonates, elderly, fulminant meningococcemia, with concomittant alcoholism, DM, MM, head trauma, Osler triad

Mechanism of death:
Bacteremia and hypotension, brain swelling, aspiration pneumonia
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Prognosis and sequelae

Residual neurologic deficits are found in 25% of H. influenzae, and 30% with pneumococcal meningitis Cranial nerve palsies tend to resolve after a few weeks or months Only half with deafness resolves Hydrocephalus

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

BACTERIAL ENCEPHALITIS

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Bacterial Encephalitis
Mycoplasma pneumoniae associated with
neuritis, myositis, meningitis, encephalitis

Listeria monocytogenes focal, rhombencephalitis

Legionella often fatal, cerebellar and brainstem

Catscratch Anthrax Brucellosis Whipple
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Subdural empyema
An intracranial suppurative process between the inner surface of the dura and the subarachnoid
Usually originates from the frontal or ethmoid sinuses, 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 anaerobic streptococci

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

SUBDURAL EMPYEMA

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

 Symptoms and signs: local pain and tenderness 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 the sinuses or other cranial structures, develops meningeal symptoms or focal neurologic signs
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

CT scan: may show mastoiditis or osteomyelitis and 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 drainage coupled with antibiotic therapy Untreated death within 6 days Treated mortality rate 25-40% because of late diagnosis
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Mass effect

Subdural empyema and arterial infarct in a patient with bacterial meningitis.

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Empyema from Otitis

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

EPIDURAL ABSCESS

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Almost invariably associated with osteomyelitis in a cranial bone Pus accumulate on the outer surface of the dura

Localizing neurologic signs are usually absent

LP is not advisable Usually due to Staphylococcus aureus Antibiotics Surgical drainage

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Chronic mastoiditis and epidural empyema in a patient with bacterial meningitis

This axial computed tomography scan shows sclerosis of the temporal bone (chronic mastoiditis), an adjacent epidural empyema with marked dural enhancement (arrow), and the absence of left mastoid air.

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

SEPTIC THROMBOPHLEBITIS

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Infection involving the dural sinuses, the ones usually involved are the lateral, cavernous and petrous sinuses

Extension from the middle ear, mastoid cells, paranasal sinuses and skin around the upper lip, nose and eyes Streptococci and staphylococci
Fever, intracranial hypertension, cranial nerve palsies and gaze abnormalities Prolonged antibiotic treatment is the mainstay of treatment
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

The MRI demonstrates left cavernous sinus enlargement, decreased caliber of the left internal carotid artery, sphenoid and ethmoid sinusitis, posterior fossa empyema, and suppuration of the left internal auditory canal.

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

BRAIN ABSCESS

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Encapsulated or free pus in the substance of the brain 40% come from infection of the middle ear, mastoid cells, and PNS
50% hematogenous from heart and lungs

20% source cannot be ascertained

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Etiology
Virulent streptococci, anaerobic and microaerophilic most common (lungs and sinuses)

In combination with other anaerobes like Bacteroides, Propionibacterium E. coli, Proteus Enterobacteriaceae (ears)
Staphylococci
The type of organism depend on the source of abscess
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Pathology
Septic thrombosis of vessels tissue necrosis
local suppurative process Within several days, the infection become delimited and the center of the infection takes on the character of pus As the abscess becomes more chronic, the periphery grows granulation tissue and later on, collagenous connective tissue ->capsule The capsule is thinner on the ventricular side

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Clinical manifestations
Headaches is the most frequent initial symptom
Drowsiness and confusion, focal or generalized seizures, focal neurologic deficits

Fever and leukocytosis are not consistently present especially during the encapsulated stage of the abscess The symptoms may evolve in a treacherous and unpredictable course even if the patient seems stable because of rupture of the abscess!

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Diagnosis
Contrast enhanced CT and MRI most important. If negative, there is almost no likelihood of abscess Blood cultures, esp with acute endocarditis

ESR
Chest xray

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Mastoiditis with developing cerebellar abscess

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Treatment
During the stage of cerebritis and early abscess formation:
Antibiotics: Pen G or third gen cephalosporin AND either chloramphenicol or metronidazole for staphylococcal infection: Nafcillin or vancomycin

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

If abscess is deep, stereotactic aspiration is the current method of choice.

FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

CT scan showing a brain abscess before (A) and after (B) aspiration

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Prognosis
If the treatment is started while the patient is 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

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Subacute and Chronic Meningitis

Induce an inflammation of the meninges of lesser intensity and chronicity The organisms are more difficult to detect and culture
TB meningitis
Neurosyphilis

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Tuberculous meningitis
Caused by the acid-fast Mycobacterium tuberculosis and exceptionally by M. bovis and

M. fortuitum

There has been a steady decrease in the cases of TB since WW II, but since 1985, there has been a moderate increase again mainly, but not exclusively, because of HIV epidemic

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Pathogenesis
First, a bacterial seeding of the meninges and subpial regions of the brain and formation of tubercles Followed by the rupture of one or more of these tubercles and discharge of bacteria into the subarachnoid space

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Pathologic findings
Meningitis is most intense in the basal meninges

Unlike the typical bacterial meningitis, the disease is not confined to the subarachnoid space and invades the underlying brain (meningoencephalitis) Cranial nerves are frequently involved

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Pathologic findings
Arteries become inflamed and occluded leading to infarctions Hydrocephalus forms because of blockage of basal cisterns

Multiple spinal radiculopathies and cord compression occurs if the exudate predominate around the spinal cord

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Exudates are seen at the base of the brain (cranial nerves and major arteries, circle of Willis)

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Clinical Features
Occurs in persons of all ages
Initially, low grade fever, malaise, headaches, lethargy, confusion, and stiff neck with Kernig and Brudzinski 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 of the onset

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Diagnosis
CSF:
Slightly cloudy or ground-glass appearance with formation of a clot on standing WBC 25-500 per cu. mm with lymphocytic predominance Sugar 20-40mg/dl Increased protein (+) AFB smear in 20-30% (+) TB-PCR (-) serology for Cryptococcus and Syphilis
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

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

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Tuberculoma behaving as an expanding mass lesion

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Basal exudates in TB meningitis with concommitant hydrocephalus

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Treatment
Quadruple anti-TB for 2 months (INH, RIF, PZA, ETH) then followed by 16-22 months of at least double anti-TB antibiotics (INH, RIF). Philippines high rates of INH-resistant organisms

Corticosteroids, in conjunction with anti-TB drugs, may be used who have subarachnoid block or raised intracranial pressure Tuberculomas that do not disappear with medication may be excised if there is a mass effect

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Prognosis
Overall mortality is still significant at 10%, infants and the elderly being at greatest risk HIVpositivepatientshavehighermortality 21% When coma has supervened before treatment, mortality is at 50% 20-30% of survivors have residual neurologic sequelae
FEUNRMF MEDICINE NEUROLOGY

Department of

Section of

Neurosyphilis
Caused by a slender, spiral, motile Treponema pallidum The treponeme invades the CNS within 3-18 months of inoculation The initial event is a meningitis which occurs in 25%. The meningitis can be asymptomatic and can only be discovered by LP! Asymptomatic neurosyphilis is the most important form because treatment at this stage can prevent further symptomatic varieties.
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Treponema pallidum

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Principal Types
Asymptomatic abnormal CSF Meningovascular meningitis and strokes Parenchymatous
Tabetic pain, paresthesia, ataxia caused by posterior spinal root and dorsal column changes Paretic personality changes, convulsions, dementia (dementia paralytica) Optic atrophy vision loss and pallor of optic discs

Spinal- chronic fibrosing myelitis or meningovascular complications

Nerve deafness and vestibulopathy
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Diagnosis and Treatment

Syndrome consistent with neurosyphilis
Abnormal blood titer of a treponemal antibody test
(+) nontreponemal antibody test in CSF

Treatment high dose IV penicillin 18-24M U for 14 days

All forms of neurosyphilis should be reexamined every 3-4 months; CSF examination after 6 months

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Other spirochetal infections

Lymesdisease caused by Borrelia burgdoferi
from tick bites
Erythema chronicum migrans Acute radicular pain followed by chronic lymphocytic meningitis and frequently with peripheral and cranial neuropathies Heart and articular surfaces are also affected

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

Other spirochetal infections

Leptospirosis caused by Leptospira interrogans
rare cause of encephalitis, myelitis, optic neuritis, neuritis

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY

CASE
19 year old female, college student, with 1week history of fever and headaches. With history of acne vulgaris over the forehead and above the bridge of the nose Pertinent VS: tempt 39 C Pertinent neurologic exam: drowsy, utters incomprehensible words, spontaneously moves all extremities equally; Bilateral Babinski sign; (+) nuchal rigidity
FEUNRMF
Department of

MEDICINE

Section of

NEUROLOGY

Thankyouforlistening.

Maria Grace Ang-De Guzman, MD Regina Victoria Reyes, MD Greg David Dayrit, MD Maricar Yumul, MD Robert Barja, MD

FEUNRMF

Department of

MEDICINE

Section of

NEUROLOGY