Neurology 4 Cardinal Manifestations of CNS Infection

CNS Infections 1. Fever

- Very important
Characteristics of CNS Infection - But there may be some infection in the CNS wherein fever is
- Occur within a closed anatomic space not prominent
- The brain is well-protected by the skull - Generally, CNS infections has to have fever
- Natural history often differs from other infectious illness at other 2. Headache
sites, even if the same organism is the cause 3. Alteration in consciousness
- Clinical manifestations differ 4. Focal neurologic signs
- Associated with high mortality - If there is brain substance involvement
- May be in the form of weakness, seizures, or behavioral
Definition of Terms changes especially if the frontal lobe is involved

1. Meningitis Note: Because of the vague presentation of CNS infections, narrowing

- Inflammation of the subarachnoid space down the differential diagnosis will be possible if age, locale, time of the
- Usually pertains to the leptomeninges year & other epidemiologic factors are considered
Ex. Influenza infection – more common in children
2. Encephalitis Pneumococcal infection – more common in adults
- Inflammation of the brain tissue Hx of travel to Palawan – consider malaria (fever, chills)
Travel from Leyte – Schistosoma infection
3. Meningoencephalitis Travel in the United States – depending on the season, some
- Meningitis & encephalitis occurs may present with predilection to viral or bacterial meningitis
- Both meninges & brain parenchyma
Clinical Manifestations of Meningitis
Notes: - Meningeal irritation
** Usually if you have meningitis, it follows that there will be infection of - Encephalopathy
the brain parenchyma. Patient may present with seizures which - Increased ICP
connotes the involvement of the brain tissue.
** Etiological differences: 1. Meningeal Irritation
- Virus is the only one that causes encephalitis while bacteria Headache/vomiting with:
rarely causes encephalitis a. Nuchal rigidity
- Bacteria & virus can both cause meningitis b. (+) Brudzinski
** The brain is an immune-privileged part of the body. Infection may c. (+) Kernig
only be localized especially if bacteria is the pathogen because of the
limiting activity of the immune system ** Brudzinski & Kernig sign are important maneuvers especially in
** Pathological differences: children and infants who cannot relate their feelings.
- Only bacteria can cause abscess in the brain
- Virus affectation leads to brain tissue involvement 2. Encephalopathy
- Some viruses affect only one part of the brain; some can - Altered mental state
affect the whole brain (this is due to differences in receptors - May start with lethargy, then becoming stuporous then
- Herpes zoster – special affectation in the anterior root they go into coma
ganglion - Seizure
- Virus-causing poliomyelitis go only to certain parts of the - May be because of cortical irritation of the infection
brain; does not affect the whole brain - Focal neurologic deficits, usually bilateral
- Weakness or hemiparesis due to vascular infarcts
Routes of Infection secondary to infection
- Hematogenous - Language problem due to involvement of the dominant
- From distant foci of infection hemisphere
- By parenteral entry
- Direct extension 3. Increased ICP
- Sinusitis Headache/vomiting:
- Otitis a. Papilledema (pale optic disc, distorted blood vessel in
- Mastoiditis funduscopy)
- Dental infections b. Diplopia with internal squint (lateral rectus palsy secondary
- Direct introduction to CN VI nerve lesion)
- Head trauma - Most patients will have a difficulty walking because of
- Neurosurgical procedure double vision or diplopia
- Lumbar puncture c. Deterioration in the level of consciousness
- Spinal anesthesia - Patient may start sleeping & drowsy and then if not
able to correct their ICP, they can become comatose
Locations d. Bulging fontanel, separation of sutures, rapid enlarging head
- Brain parenchyma size
- Encephalitis - Usually in infants
- Abscess Lateral Rectus Paralysis
- Subarachnoid space Papilledema (Px is looking to the right)
- Meningitis
- Subdural space
- Subdural empyema
- Epidural space
- Epidural abscess
- Venous thrombophlebitis (especially in the danger zone in the
paranasal area causing the following :)
- Cavernous sinus
- Transverse sinus ** 3 CN involve in EOM. CN III, IV and VI. Any of these 3 nerves
may be affected by increased ICP. But CN VI is the most
commonly involved in cases of ↑ ICP
CSF Analysis Note:
Normal CSF Abnormal CSF ** In some cases, you may also have infarction because the cerebral
• Clear, colorless (water-like) • Pleocytosis of >1000 blood vessels have been involved. In this case, px may present with a
• Not more than 180mm of cells/cumm with predominance stroke-like complication due to the microorganism or obstruction to the
water of PMNs suggests bacterial blood supply of the brain.
• WBC less than 5cell/cu.mm meningitis or acute purulent
• Total protein 15-45 mg/dL meningitis - 80% of bacterial meningitis are caused by the following 4
• Sugar 40-50% of the RBS • Fewer WBC <1000 cells/cumm organisms:
with a predominance of 1. S. pneumoniae
• Negative for microorganism
lymphocytes suggests viral, 2. N. meningitidis
growth on culture
mycobacterial or fungal 3. S. Aureus
meningitis 4. H. influenza type B
RBS – random blood sugar (Compare CSF results with RBS)
** Sugar content: How do you differentiate those 4 organisms? (Examples)
Bacterial, mycobacterial & fungi meningitis – low sugar content ** If an outbreak of meningitis occurs in a refugee center (because of
Viral meningitis – normal sugar content flash floods), most common cause would be meningococcal meningitis.
** Protein content: ** Take note of the patient’s age, situation to delineate which pathogen
Acute purulent bacterial meningitis – protein is markedly elevated is responsible for the meningitis
Viral meningitis – protein is slight elevated only
** Color/consistency Pathophysiology of Bacterial Meningitis
Xanthochromic – consider hemorrhage
Turbid – consider infection
** Pleocytosis >5-10 cells/cumm; in acute purulent bacterial
meningitis, it is elevated at >1000

Etiologic Agents
1. Bacteria
2. Fungi
3. Virus
4. Others
- Spirochete
- Rickettsia, mycoplasma, chlamydia
- Parasite (Helminths, Protozoa)

General Syndromes
- Acute Meningitis Syndrome
- Subacute or Chronic Meningitis Syndrome
- Acute Encephalitis Syndrome
- Chronic Encephalitis Syndrome
- Space-occupying Lesion Syndrome
- Toxic-mediated Syndrome
- Encephalopathy with Systemic Infection
- Postinfectious Syndrome
- Slow Viral Diseases – simulates the degenerative disorders

ACUTE MENINGITIS
- Most familiar & most feared
- Acute onset (few hours to a few days)
- Symptoms: Patient Characteristic Biological Organisms
- High fever Neonate Group B streptococcus
- Headache E. coli (UTI)
- Photophobia Children H. influenza
- Stiff neck N. meningitides
- Altered mental state Adults S. pneumoniae
- Etiology: (specific predisposing conditions) Older (>50) S. pneumoniae
- Bacterial infection of the paranasal sinuses or mastoids Enteric gram (-) bacilli
- Recent neurosurgical procedure (E. coli, pseudomonas)
- Bacteria & viruses (“aseptic meningitis”) – the 2 leading causes Neurosurgical pxs Staphylococci
- Viral meningitis is considered “aseptic” because when you (cranial trauma) Gram (-) bacilli
culture CSF, it is usually sterile or you won’t be able to Immunosuppressed Gram (-) enteric bacilli
identify the microorganism; also there is normal CSF but Neutropenia Staphylococci
with slight pleocytosis TB and Cryptococcus
- Improves or resolves completely within a few days if correctly (common in
diagnosed & treated immunosupressed)
- 2 Types: Immunoglobulin deficiency S. pneumoniae
1. Bacterial Meningitis (alcoholic, postsplenectomy) H. Influenza
2. Viral Meningitis N. meningitidis
T-lymphocyte and macrophage L. monocytogenes
Bacterial Meningitis (Acute Purulent Meningitis) deficits (AIDS, renal transplant,
- Acute purulent infection in the subarachnoid space associated chronic steroid use)
with an inflammatory reaction in the brain parenchyma & cerebral
blood vessels that causes the ff: Note: Neonates & adults have different manifestations of meningitis.
- ↓ consciousness This lecture pertains to adult meningitis only. In neonates & infants,
- Seizure activity you should have a high index of suspicion. Fever, poor suck, lethargy in
- ↑ ICP infants & neonates should make you suspect of meningitis.
- Stroke
Streptococcus pneumoniae Clinical Manifestations by Age Group
- Most common etiologic organisms of community-acquired
bacterial meningitis in children & adults - Neonates & Infants
- Caused by: (associated conditions) - Fever (50%)
- Pneumonia - Lethargy
- Otitis media - Poor feeding
- Sinusitis - Irritability
- CSF fistulae - Vomiting & diarrhea
- Alcoholism - Apnea
- Head injury - Seizures
- Bulging fontanel
Neisseria meningitidis
- Nonspore-forming, nonmotile, oxidase-positive, gram (-) cocci or - Children & adults
kidney-shaped diplococci - Fever
- Disease exclusive to humans - Headache
- Nasopharynx is the natural reservoir - Photophobia
- N. meningitidis is naturally present in the nasopharynx. But - Nuchal rigidity
somehow, something happened that made it spread to the - Lethargy, stupor, confusion, coma
brain - Seizures
- Transmission by airborne droplets or close contact - Focal neurological deficits
- Time from nasopharyngeal acquisition to bloodstream invasion is - Nausea & vomiting
short (~10days)
- Once the organism is blood-borne over 90% of meningococcal - Older adults
disease is manifested as meningitis &/or meningococcemia - Fever
- At this stage, the disease is very contagious. Everybody - Headache
who had contact with this px should receive prophylaxis. - Nuchal rigidity
- Confusion or coma
Gram (-) bacilli - Seizures
- ~84% of cases of neonatal meningitis & sepsis attributed to E. coli
- Neurosurgical, alcoholics & in pxs with underlying lung CA, Diagnosis of Bacterial Meningitis
diabetes, CHF, chronic pulmonary disease, hepatic & renal Routine CSF Examination
disease Purulent meningitis Normal values

opening pressure <180-200 mmH2O
Listeria monocytogenes Gross appearance turbid or Clear & colorless
- Common among immunocompromised pxs purulent

WBC (mostly PMN) <5 mononuclears
S. aureus (-) polymorphonuclears
- In neurosurgical procedures
protein 15-45 mg%
Low glucose (<50% RBS) 50-60 mg% or

Streptococcus agalactiae or GBS
- Leading cause of bacterial meningitis & sepsis in neonates Other diagnostic procedures:

Gram stain
H. influenza type B
Culture & sensitivity
- Most common causative organism of bacterial meningitis in
Bacterial antigens
children
- Small, gram (-) pleomorphic coccobacilli ** CSF may appear cloudy or turbid, greenish or yellowish in color
- Grows best in anaerobic medium especially in purulent meningitis. (Pineapple juice-like)
Classic CSF Analysis of Bacterial Meningitis
- ↑ opening pressure Base of the brain in an acute case
- Pleocytosis of PMN leukocytes (10-10,000 cells/cumm) of pneumococcal meningitis
- ↓ glucose concentration (<45mg/dL) showing abundant purulent
- ↑ protein concentration exudate especially prominent in
the cisterns
** Use Latex agglutination (LA) test for detection of bacterial antigens. ** Bulk of the exudates is
Also gram staining & culture & sensitivity are appropriate diagnostic usually in the convexity of the
tests. cerebrum
** Before getting these lab results, you should already have a suspicion ** For more prolonged cases,
& antibiotics are imperative to have been started soon. You cannot exudates appear in the base of
delay treatment to avoid complications. Just change antibiotics when the brain
the lab results come out.

Antimicrobial Therapy

Organism Antibiotic Adverse Effects

S. pneumoniae Ceftriaxone or Eosinophilia, biliary
cefotaxime + pseudolithiasis,
vancomycin nausea, vomiting
N. meningitidis Pen G & ampicillin Rash, nausea,
vomiting
Gram (-) bacilli Cefotaxime or Nausea, vomiting,
ceftriaxone diarrhea, eosinophilia
L. monocytogenes Ampicillin + gentamicin Nephrotoxicity & Contrast-enhanced CT image of Meningeal enhancement in
ototoxicity a 3mo-old baby brain showing bacterial meningitis
brain edema & subdural
S. agalactiae Pen G Rash
empyema
 Ventriculitis, shunt S. epidermidis, Meropenem +
infection S. aureus, Vancomycin
Gram (-) Enterobac,
P.aeruginosa
Immunocompromised L. monocytogenes 3rd or 4th gen.
or older pxs (impaired Gram (-) Enterobac, cephalosporin +
cellular immunity) P. aeruginosa, Ampicillin +
Pneumococci Vancomycin
Diffuse pial meningeal Focal left cerebral
Antibiotics Commonly Used in the Treatment of Bacterial
enhancement meningitis
Meningitis in Children & Adults
** What we do before a lumbar puncture is administer antibiotics and Medication Dose
request for CT or MRI. Absence of abscess or any space-occupying Ampicillin Child: 300-400 mg/kg/d (q4h)
lesion is a go signal for the lumbar puncture. But if these are present, Adult: 12-15 g/d (q4-6)
lumbar puncture is a contraindication. Ceftriaxone Child: 80-100 mg/kg/d (q12h)
** If CT or MRI is not available (like in the remotes areas), Mannitol can Adult: 4 g/d (q12h)
be used to decompress the brain before doing the lumbar puncture to Cefotaxime Child: 300 mg/kg/d (q6h)
prevent complication of herniation. Adult: 12 g/d (q4h)
Ceftazidime Child: 6 g/d (q8h)
Principles of Treatment in Meningitis Cefepime Adult: 4 g/d (q12h)
1. Always treat as a medical emergency. Fosfomycin 15 g/d (q8h)
2. Prompt and appropriate antibiotic therapy. Meropenem 6 g/d (q8h)
3. Cerebral metabolism should be protected. Nafcillin Child: 200-300 mg/kg/d (q4h)
4. Monitor ↑ ICP by clinical sings including BP, serial measurements Adult: 9-12 g/d
of head and if available, intracranial sensors Rifampin 600-1200 mg/d (q12h)
5. Prevention and control of seizures Gentamicin, 6 mg/kg/d (q8h)
6. Fluid management should strive for normovolemia of SIADH and tobramycin
hypovolemia of dehydration. TMP-SMX 15-20 mg/kg/d of TMP component (q8h)
7. Control of hyperpyrexia because it increases cerebral metabolic Metronidazole 1500-2000 mg (q8h)
demand.
Vancomycin Child: 60 mg/kg/d (q6h)
Adult: 2-3 g/d (q6-12h)
Antibiotic Penetration into CSF from Blood
Chemoprophylaxis of Meningococcal Meningitis
Antibiotic Normal Meningitis
** To those individuals who are exposed to people with meningococcal
Meninges
infection
Penicillin G Poor Fair-good
Antibiotic, Age group Dosage
Ampicillin Poor Fair-good
Rifampin
Nafcillin Poor Fair Adults 600 mg q12 for 2 days PO
Ticarcillin/Piperacillin Fair Fair-good Infants ≥ 1 mo 10 mg/kg q12 for 2 days PO
Ceftriaxone Fair Good Infants ≤ 1 mo 5 mg/kg q12 for 2 days PO
Cefotaxime Fair Good
Ciprofloxacin
Ceftazidime Fair Good Adults 500 mg as single dose PO
Gentamicin Poor Poor-fair Ceftriaxone
Amikacin Poor Poor Adults & children ≥ 15 y/o 250 mg as single dose IM (or IV)
Tetracycline Poor Fair Children < 15 y/o 125 mg as single dose IM (or IV)
Doxycycline Poor-fair Fair
Chloramphenicol Good Good Dexamethasone
Rifampicin Fair Good
Vancomycin Poor Fair-good Rationale:
Erythromycin Poor Poor-fair – May ↓ ICP by ↓ meningeal inflammation and brain water content
Sulfonamides Fair-good Good – May ↓ sensorineural hearing loss and other neurologic
Clindamycin Poor Fair complications
Aprofloxacin Good Good – May modulate production of cytokines, which in turn, lessens the
Ofloxacin Good Good meningeal inflammatory response

Initial Empiric Antibiotic Therapy of Bacterial Meningitis Indications:

– H. influenzae meningitis
Age group/clinical Typical pathogen Recommended – May be considered in pneumococcal and meningococcal
setting Initial Antibiotic meningitis, although its efficacy for these infections is unproven
Newborns Gram (-) Enterobac (E. Cefotaxime + – Partially treated meningitis NOT an indication
coli, Klebsiella, Ampicillin
Enterobacter, proteus), Regimen:
Group B strep (S. – Dose: 0.6 mg/kg/day in 4 divided doses, IV, for the first two days
agalactiae) of antibiotic therapy or 0.8 mg/kg/day in two divided doses
Infants & children N. meningitides, Ceftriaxone or – Administer at time of or shortly before the first dose of
S. pneumoniae, cefotaxime + antibacterial therapy
H. influenza Vancomycin
Healthy adult, S. pneumoniae, 3rd or 4th gen.
immunocompetent, N. meningitidis, cephalosporin +
community-acquired L. monocytogenes Ampicillin +
Vancomycin
Nosocomial Gram (-) Enterobac, Meropenem +
(postneurosurgery or P. aeruginosa, Vancomycin
posttraumatic brain Staphylococci
injury)
Cerebral Complications of Bacterial Meningitis VIRAL MENINGITIS
1. Brain edema with risk of herniation Pathogenesis: Steps in Hematogenous Spread of Virus to CNS
2. Cerebrovascular involvement—most frequent 1. Entry into host through inoculation, respiratory or enteric route
- Cerebral arterial complications: 2. Growth in extraneural tissues
- Arteritis 3. Viremia
- Vasospasm 4. Viral crossing from the blood
- Focal cortical hyperperfusion a. small vessels to brain (encephalitis)
- Disturbed cerebral autoregulation b. choroids plexus to CSF (meningitis)
- Septic sinus thrombosis & cortical venous thrombosis
3. Hydrocephalus (communicating or obstructive type) Etiology
- Especially if meningitis is prolonged & unresponsive to A. Viral Meningitis
medication 1. Enterovirus (coxsackie, echovirus) – most common
- Because of the thickening of the CSF 2. Mumps
4. Vestibulocochlear involvement (hearing impairment, 3. Herpes simplex type 2
vestibulopathy) 4. Lymphocyte choriomeningitis (LCM)
5. Cranial nerve palsies—CN II, III, VI, VII, VIII 5. Adenovirus
6. Cerebritis
7. Sterile subdural effusion B. Viral Encephalitis
8. Rarely as a consequence of meningitis: brain abscess, subdural 1. Arthropod-borne (Japanese B Encephalitis)
empyema 2. HSV Type 1 (labialis)
- If infection is not controlled promptly & properly 3. HSV Type 2 (genitalis)
4. Varicella Zoster Virus
Spectrum of Complications in Pneumococcal Meningitis 5. Cytomegalovirus
1. Septic shock 6. EBV
2. Diffuse brain edema 7. HIV
3. Seizures 8. Other viruses
4. Hydrocephalus ** HSV is the only microorganism that is responsive to treatment. The
5. Arterial CV complication others are usually self-resolving or microorganisms die eventually.
6. Venous CV complication
7. Spontaneous intracranial hemorrhage Diagnosis
8. Cerebritis 1. CSF Examination
9. CN palsies a. Clear colorless
10. Spinal cord dysfunction - May be bloody in herpes simplex encephalitis
11. Hearing loss b. Slight to moderate pleocytosis with either PMN or
12. DIC mononuclear predominance (Cell counts do not reach high
13. Renal failure counts. Only until 200-300. Unlike in purulent, which
14. Requiring hemofiltration reaches up to 1000 cell counts)
15. Adult RDS c. Proteins mild to moderate increase occasionally elevated
IgG concentration
** 1, 2, 3 are the top 3 complications d. Glucose normal but decreased in mumps, herpes simplex
and lymphocytic choriomeningitis
Mortality Rates of Bacterial Meningitis in Adults 2. PCR
3. Viral culture
Bacterial Pathogens Mortality Rate (%) ** A completely normal CSF does not rule out encephalitis
Pneumococcal meningitis 20-35
Meningococcal meningitis 3-10 Pathology
Listeria meningitis 20-30 - Parenchymal brain infection almost invariably associated with
Staphylococcal aureus meningitis 20-40 meningeal inflammation
Gram (-) meningitis 20-30 - Perivascular and parenchymal mononuclear cell infiltrate
- Microglial nodule
** In a recent study, dexamethasone significantly reduced mortality - Neuronophagia
rates of pneumococcal meningitis in adults to 14% (34% in the placebo - Herpes simplex encephalitis:
group) - Hemorrhage
- Necrotizing encephalitis
- Most severe along the inferior & medial surface of temporal
lobes and orbitofrontal gyri
- Due to the involvement of these areas, patient present
with behavioral changes, altered sensorium, focal
seizures

Herpes Simplex Encephalitis

- Common sporadic viral encephalitis
- A notorious disease
- Hemorrhagic lesions (temporal & basal temporal lobe)
- A distinct pathology in the midline or at the base or inferior
meningeal surface of the temporal lobe
- Cowdry A inclusion bodies
- Culture & PCR
- Treated with Acyclovir 10mg/kg/d IV q8h for 10-14 days

Treatment
Acyclovir
- Only viral conditions treated with medications:

Herpes simplex

Varicella zoster
- Dose 10 mg/kg/d IV q8h for 10-14days
 SUBACUTE OR CHRONIC MENINGITIS SYNDROME
- Course over weeks, months or years
- Clinical findings are same as acute meningitis but the time course
is quite different
- Fever tends to be lower & hectic
- Focal neurological findings are common
- Caused by a variety of microorganism (TB, Cryptococcus,
spirochetes, etc)
- Meningeal TB is more difficult to diagnose or exclude, often it
should be treated empirically while evaluation continues
Petechial hemorrhages in the Extensive right basal ganglia
subcortical white matter of the & internal capsule infarcts
TB Meningitis
brain as a result of TB after the appearance of
- 8M years
meningitis-associated vasculitis vasculitis in the
- Brain damage if untreated
- Tuberculoma – 10-20% thalamoperforating arteries in
- First few days of anti-TB does not affect the ability to culture MTb a child treated for TB
from the CSF – do not withheld tx meningitis
- Solid media culture – 4-6wks
- BACTEC radiometric system (Middlebrook 7H10, Lowenstein-
Jensen or liquid culture system – 1-3wks) Note:
- PCR assay – rapid method of detecting TB DNA; but not very ** Px presents with 2 wks of fever, headache, and lethargic, stiff neck.
efficient When you do a lumbar tap, pressure is 250-300. CSF is thick or turbid.
If lab results confirm meningitis, immediately start with anti-cox
Pathogenesis of TB Meningitis treatment right away

Initial infection
** Infarcts in TB meningitis
Late reactivation of foci outside the
- Blood vessels will traverse the subarachnoid space and it is a
CNS
chronic infection of the CSF, then you develop vasculitis
because of its proximity  obstruction  thrombosis 
Bacteremia infarct

TB meningitis does not develop by direct & immediate
hematogenous invasion in the meninges
Isolated miliary tubercles throughout the substance of the
brain & meninges
General Principles in the Treatment of TB Meningitis
– Multiple antimicrobial drugs are required
– Drugs must adequately cross the BBB
– Drugs should be taken on a regular basis
– Drugs should be taken for a sufficient period to eradicate the CNS
infection

Treatment of TB Meningitis
Large caseous foci - Drug resistance to MTb is low
- Suspect if px has been previously treated for TB or has
come from a part of the world with high prevalence of drug
If located adjacent to ependyma may rupture into resistance
subarachnoid space (“rich foci”) - First line drug regimen – INH, Rifampicin, Pyrazinamide with
addition of Streptomycin or Ethambutol
Diagnosis - 9-12 mos – most circumstances
- 6 mos – excellent clinical response
CSF Examination - 18-24 mos – poor response
1. Opening pressure—increased 1. INH
2. Gross appearance—clear or turbid (pellicle formation) - Bactericidal
3. Increased WBC—mostly lymphocytes - Impairs TB DNA synthesis
4. Increased protein 2. Rifampicin
5. Low glucose - Bactericidal
6. (+) AFB stain - Impairs TB RNA synthesis
7. Culture & sensitivity 3. PZA
8. TB Bactec - Kills slowly metabolizing mycobacteria
4. Streptomycin
- Bactericidal
- Given for 2 mos only due to sensorineural hearing loss
5. Ethambutol
- Bacteristatic
- Less effective than streptomycin
- Given for 2 mos
- Second line anti-TB drugs
- Ofloxacin
- Ciprofloxacin
- Kanamycin
- Amikacin
- Corticosteroids – adjunctive therapy recommended for severely ill
Marked enhancement in the pxs for the first 1-2mos
Thick-walled abscess
basal cistern & meninges with
dilatation of the ventricles
 Time course Drugs Doses Treatment of Cryptococcal Meningitis
First 2 months Daily Phase Drug Adverse Effects
Isoniazid 10-15 mg/kg/d Initial 4-8 wks Amphotericin B Nephrotoxicity
Rifampicin 10-20 mg/kg/d Anaphylaxis
Pyrazinamide 25-30 mg/kg/d Flucytosine Bone marrow
Ethambutol 15-25 mg/kg/d suppression
Streptomycin 15-40 mg/kg/d
Next 7-10 months Daily Maintenance Fluconazole Hepatotoxic
(Total of 9-12 mos) Isoniazid 10-15 mg/kg/d SJS
Rifampicin 10-20 mg/kg/d Anaphylaxis

** Cryptoccocal meningitis is very indolent. Be very vigilant & px in

Drug Adverse Effect/s treating this.
Isoniazid Hepatic Toxicity
ACUTE ENCEPHALITIS SYNDROME
Peripheral neuropathy (can be
prevented with pyridoxine) - Often co-exist with acute meningitis (meningoencephalitis).
Phenytoin toxicity - Lesion may either be focal or diffuse
- Early abnormalities of mental status (prior to the onset of
Rifampicin Hepatic toxicity
obtundation or coma) and seizure is higher compared to acute
Interstitial nephritis
meningitis
Ethambutol Optic neuropathy
- Herpes Simplex Encephalitis - only treatable viral encephalitis
Pyrazinamide Hepatic toxicity
Arthralgia with hyperuricemia CHRONIC ENCEPHALITIS SYNDROME
Streptomycin Vestibular toxicity - Shares many clinical features with AES however, the onset is
gradual and the course is less hectic.
- Prednisone 1-2 mg/kg/d or its equivalent for 6-8wks to reduce - Less dramatic findings and less severe but often they progress
vasculitis, inflammation, and ultimately intracranial pressure gradually to severe disability or death.
- Hydrocephalus: use ventriculoperitoneal shunt - Patient presents a picture of greater debility rather than acute
- Supportive measures illness.
- Segregation from infection source - Complications are more common (pressure sore, contractures, or
dementia) during the course
Cryptococcal Meningitis
- Most common form of fungal meningitis SPACE-OCCUPYING LESION SYNDROME
- Seen in human immunodeficiency virus (HIV), and among
immunocompromised patients Brain Abscess
- Pathogen: Cryptococcal neoformans - Focal intracranial infections most challenging neurological
- Respiratory tract – typical portal entry condition – diagnosis and management
- 90% - headache - Difficult to localize at early stage
- 50-60% - fever, nausea, vomiting, altered sensorium with signs of - Requires coordinated effort to several disciplines (neurosurgeon,
inc. ICP intensivist, infectious disease specialist)

Etiopathogenesis
Pathogenesis - Direct bacterial implantation as in trauma or surgery
- By contiguity from infections of the mastoid or paranasal sinuses
- Sinusitis  frontal lobe
- Mastoiditis  temporal lobe or cerebellum
- By hematogenous route:
- from remote infection as a consequence of sepsis
- in association with a cardiopulmonary malfunction such as
cyanotic congenital heart defects
- If from the heart, usually from the middle cerebral
artery since it has the direct connection with the carotid
system; can go anywhere
- unknown

Etiology
- Most common: Streptococcus
- Anaerobic and microaerophilic streptococci
- Fusobacterium species
- β-hemolytic streptococci
CSF Examination - S. aureus
1. Routine CSF Examination - Less common
- opening pressure is increased - Actinomyces
- clear CSF but may occasionally be turbid - Bacteroides
- moderate pleocytosis with lymphocytosis - H. influenza
- elevated protein
- low glucose
2. Stain: India ink
3. Cryptococcal Antigen Latex Agglutination (CALAS)
4. Culture: Saboraud’s medium

** CSF examination of cryptococcal meningitis is the same with TB

meningitis except in the efficiency of staining for cryptococcal
meningitis with India ink & culture. In TB meningitis, no concrete proof
from staining & culture can be seen.
Predisposing Conditions & Likely Pathogens in the Brain Abscess
Predisposing Conditions Likely Pathogens
Ear infection Anaerobes, gram (-) aerobes,
streptococci,
H. influenza (children)
Dental sinuses Streptococcus, anaerobes
Trauma, surgery S. aureus, S. epidermidis,
Gram (-) aerobes
Abdominal, pelvic streptococci Anaerobes, gram (-) aerobes,
infections
Endocarditis S. aureus, S. epidermidis,
Gram (-) anaerobes,
Streptococci, drug usage,
Fungi
HIV/T-cell dysfunction Toxoplasma, Aspergillus, Candida,
Nocardia, Mycobacteria, Listeria,
Salmonella, Cryptococcus (&
lymphoma-mimicking abscess)
Neutrophil dysfunction S. aureus, gram (-) anaerobes,
aspergillus,
Zygomycetes, Candida
Pathology of Brain Abscess
Stage Days Changes
Early Cerebritis 1-3 Local inflammatory response
seen in adventitia of blood
vessels beginning edema
with small necrotic areas
Late Cerebritis 4-9 Edema reaches maximum
with an increase in the size of
the necrotic area
Early capsule 10-13 Necrotic area is isolated from
the adjacent parenchyma by
consolidation of the collagen
network around it
Late capsule >14 Nature’s attempt to protect
the surrounding tissues from
injury with more reactive
inflammatory changes
Clinical Manifestations
- At onset, headache, vomiting, convulsions as the abscess
progress, neurologic signs become readily apparent
- papilledema
- lateralizing signs e.g. hemiparesis, homonymous
hemianopsia
- more obvious signs of increased ICP
- Insidious onset and slowly progressive
- Sudden rupture
- sudden high fever
- meningeal signs
- deterioration of consciousness
Complications
1. Seizures
- can appear anytime within 1 month and 15 years after a
supratentorial abscess
2. Localized neurologic abnormalities
3. Mental retardation in children
4. Hydrocephalus: common complication
Prognosis

Good if detected and treated early

Mortality rate has declined from 30% in the pre-CT area

In infants, mortality approaches 50%

Usual causes of death
- cerebral herniation
- fulminant meningitis when abscess ruptures into the
ventricles or subarachnoid space
TOXIN-MEDIATED SYNDROME
- Several distinctive syndrome can occur when microbial toxins that
react specifically with neural tissue reach the CNS
- Tetanus – clinical findings result from overstimulation of
neural cells
- Botulism – clinical findings result from interruption of neural
transmission.
- Least likely to show the four cardinal manifestations of CNS
infection
ENCEPHALOPATHY WITH SYSTEMIC INFECTION
- Usually the manifestations of the primary disease dominate the
clinical picture.
- Typhoid fever, malaria, etc
- Because of large and varied group of disease, syndromic
approach to diagnosis is less effective
- Should be considered as possible underlying cause whenever an
undiagnosed CNS syndrome is under evaluation.
POSTINFECTIOUS SYNDROME
- Usual sequence begins with common, rather trivial, viral infection.
- Usually most patients recover uneventfully from the infection
- Serious PI neurologic syndrome develops due to idiosyncratic
reaction to primary infection.
- GBS, PI encephalitis or meningoencephalitis, transverse
myelitis
SLOW VIRAL DISEASES
- Develop insidiously, over months or longer
- Show progressive sign of neuronal destruction, often affecting
motor function severely
- Mortality is high
- Creutzfeldt-Jacob Disease

Treatment
- Medical: only if early and late Cerebritis
- Surgical: only if abscess is solitary, superficial, well-encapsulated

Pathogen Agent/s
Streptococcus species Pen G
Ceftriaxone
Cefotaxime
Cefepime
Staphylococcal Nafcillin Notes from Dr. Ostrea & Dr. Javier are labeled with **.
Vancomycin
Gram (-) enteric Ceftriaxone Transcribed by: Denise Zaballero ☺
Cefotaxime Slides from: Fred Monteverde
Cefepime Additional notes from: Cecile Ong
Bacteroides fragilis Metronidazole Mitzel Mata
H. influenza Ceftriaxone Recorded lectures: Lala Nieto
Cefotaxime Tin Ramos
Pseudomonas Ceftazidime January 2008
Cefepime
Nocardia TMP-SMX Look at the next page!! ☺
“If in the exam I asked you” – Dr. Poblete
1. 3 most common pathogens causing CNS infections:
bacterial, fungal, viral
2. Most common bacterial pathogens:
S. pneumoniae, N. meningitidis
3. Listeria monocytogenes: common pathogen in developed
countries
4. Major route of CNS infection: hematogenous
5. In TB and fungal meningitis, inflammatory
exudates are seen at the base of the brain and the structures
involved are the cranial nerves (leading to cranial nerve deficits)
and Circle of Willis (leading to stroke-like symptoms)
6. Brain parenchymal infection:
diffuse—encephalitis
focal—abscess
7. Infection subarachnoid space: Leptomeningitis
8. Infection in subdural space: Subdural empyema
9. Infection in the epidural space: Epidural abscess
10. Infection in venous sinus: Thrombophlebitis
11. Spread of ethmoiditis: ethmoid, frontal, sphenoid sinusesanterior
cranial fossafrontal lobe
12. Spread of otitis and mastoiditis:
petrous sinusmiddle cranial fossatemporal lobe
petrous sinusposterior cranial fossacerebellum
13. Infection in the cranium may spread
retrograde via emissary vein
14. Enterovirus: Most common viral pathogen
15. Cerebellar hemispheres when affected leads to
ipsilateral incoordination
16. Midline vermis when affected leads to
truncal ataxia
17. 4 important clinical manifestations of meningitis are:
a. meningeal irritation
b. encephalopathy
c. increased ICP
d. focal neurologic deficits
18. Headache/Vomiting: most common symptoms
19. Nuchal rigidity: resistance of the neck with passive flexion
20. (+) Brudzinki sign: passive neck flexion leads to knee flexion
21. Kernig’s sign: passive knee extension with hip flexed leads to
resistance to knee extension
22. HSV encephalitis: present as diffuse inflammation but with
prominent focal deficits especially in the medial temporal and
orbitofrontal structures
23. Acyclovir: treatment of HSV encephalitis
24. The 2 most common presentations of encephalopathy: altered
mental state and seizure
25. Abducens nerve: mostly affected with increased ICP due to its
long intracranial course (more susceptible to stretching)
26. Abducens nerve palsy alone is a false localizing sign.
27. Abducens nerve palsy with papilledema is most likely due to
increased ICP
28. 2 areas that may be affected in patients with altered consciousness
are the cerebrum or the brainstem (ARAS)
29. CSF Examination is the most important diagnostic procedure to
do; lumbar puncture is only the procedure to get the sample CSF
30. In the diagnosis of purulent meningitis, one must look at the
following parameters:
a. opening pressure
b. gross appearance
c. cell count (most impt; characterized by pleocytosis)
d. protein
e. sugar
36. Most common pathogen of brain abscess: Streptococcus
37. Brain abscess: most common presentation is focal deficits + signs
of ICP. Temporal profile is insidious and slowly progressive vs. stroke
which is rapid and sudden
38. Routine CSF cannot differentiate between TB and cryptococcal
meningitis.
39. Meningococcal meningitis: has the least mortality rate/best
prognosis among the different types of bacterial meningitis
40. 3rd gen cephalosporin: good penetration in both intact and
inflamed brain
41. Ceftriaxone & Cefotaxime: for gram (-) bacteria
42. Ceftazidime: good for Pseudomonas
43. Gentamicin & Amikacin: adjuncts only and not given as
monotherapy
44. Chloramphenicol: good penetration but bacteriostatic
45. Cefepime & Meropenem: 4th gen cephalosporin with good
coverage against Pseudomonas
46. Metronidazole: given to cover anaerobes
47. Dexamethasone: used for H. influenza, pneumococcal and
meningococcal meningitis
48. Dexamethasone: not indicated for partially treated meningitis
49. Best timing of Dexamethasone administration is at the time of or
20 minutes before the first dose of antibacterial therapy
50. 3 most common complications of pneumococcal meningitis: septic
shock, diffuse brain edema, seizure
51. Acute meningitis: usually caused by viral and bacterial pathogens
52. TB meningitis: results only after rupture of military tubercles
53. Hepatotoxic drugs: Isoniazid, Rifampicin, Pyrazinamide
54. Side effect of Ethambutol is optic neuropathy
55. Streptomycin is vestibulotoxic
56. 3 drugs used to treat cryptococcal infection are Amphotericin B,
Flucytosine and Fluconazole
57. Amphotericin B is nephrotoxic
58. Flucytosine causes bone marrow suppression
59. Fluconazole is Hepatotoxic
60. Most common cause of viral encephalitis is arthropod-borne virus
(Japanese B enceph in the Phils)
61. Bloody CSF seen in HSV encephalitis
62. A completely normal CSF does not rule out encephalitis
63. Cowdry A bodies seen in HSV encephalitis
64. Brain abscess treated medically if presents with Cerebritis; treated
surgically if already with capsule
65. Hydrocephalus: most common complication of brain abscess

31. AFB stain for TB meningitis

32. 3 most common pathogens in chronic meningitis:
TB, fungus and partially treated meningitis
33. Most common pathogen in fungal meningitis: Cryptococcus
neoformans
34. 3 tests for C. neoformans:
a. India Ink stain
b. Culture on Saboraud’s medium
c. Latex particle agglutination test
35. Test of choice for C. neoformans: Latex particle agglutination
test