CNS infection

Content
 Routs
 Classification by organ involvement
 Meningitis
 Encephalitis
 Myelitis
 Classification by pathogen
 Bacteria
 Virus
 TB
 Fungus
 Spirochete
 Parasite
 INFECTIONS
4 routes which infectious agents can enter
the CNS
 hematogenous spread
i) most common
- usually via arterial
route
- can enter retrogradely
(veins)
 direct implantation
i) most often is traumatic
ii) iatrogenic (rare) via
lumbar puncture
 local extension
(secondary to established
infections)
i) most often from
mastoid and frontal
sinuses, infected tooth
 PNS into CNS
i) viruses
- rabies
- herpes zoster
 Definitions
 Meningitis
 Inflammation of the leptomeninges
 Usually caused by bacteria
 Encephalitis
 Inflammation of the brain itself
 Caused by many types of organisms
 Myelitis
 Inflammation of the spinal cord
 Meningitis classified
 acute pyogenic
 usually bacterial meningitis
 aseptic
 usually acute viral meningitis
 chronic
 usually TB, spirochetes, cryptococcus
Characteristic CSF formulas
Imaging should precede lumbar puncture

 new-onset seizures
 an immunocompromised state
 signs that are suspicious for space-
occupying lesions
 moderate-to-severe impairment of
consciousness
 Encephalitis
 Acute flu-like prodome, high fever, severe
headache, N/V, altered consciousness,
seizure and focal neurological signs
 Limbic encephalitis (temporal lobe
involvement)
 Rhombenencephalitis (lower cranial n.
involvement, myoclonus, autonomic
dysfunction, lock in syndrome)
Bacteria
 Examples of Bacteria
 Streptococcus pneumoniae
 Neisseria meningitidis
 Haemophilus influenzae
Pathogenesis
Microorganism vary with age of the patient
a) neonates
i) E. coli
ii) Strep. pneumonia
iii) Listeria monocytogenes
b) adolescents and young adults
i) Neisseria meningitidis (most
common)
ii) Haemophilus influenza
- immunizations have markedly
reduced this pathogen
Signs & Symptoms of Meningitis
 Headache > 90%
 Fever > 90%
 Stiffness of neck > 85%
 Vomiting 35%
 Seizures 30%
 Weakness 15%
 Spinal tab yields
 cloudy or frankly purulent CSF ( 100-
10,000 WBC)
 increased pressure (40% presure
>400mmH2O)
  neutrophils (80-95%)
•Respiratory isolation for 24 hours is indicated for patients with suspected
meningococcal infection
 Adjunctive dexamethasone therapy
 Dexamethasone does not improve the
outcome in all adolescents and adults with
suspected bacterial meningitis; a
beneficial effect appears to be confined to
patients with microbiologically proven
disease, including those who have
received prior treatment with antibiotics

n engl j med 357;24 www.nejm.org december 13, 2007

 Neurocritical care

 In patients with a high risk of brain herniation, consider

monitoring intracranial pressure and intermittent
administration of osmotic diuretics to maintain an
intracranial pressure of <15 mm Hg and a cerebral
perfusion pressure of > 60 mm Hg
 Initiate repeated lumbar puncture, lumbar drain, or
ventriculostomy in patients with acute hydrocephalus
 Electroencephalographic monitoring in patients with a
history of seizures and fluctuating scores on the
Glasgow Coma Scale*
 Airway and respiratory care
 Intubate or provide noninvasive ventilation in
patients with worsening consciousness (clinical
and laboratory indicators for intubation include
poor cough and pooling secretions, a RR of >35
per minute, arterial oxygen saturation of <90%)
 Maintain ventilatory support with intermittent
mandatory ventilation, pressure-support
ventilation, or continuous positive airway
pressure
 Circulatory care
 In patients with septic shock, administer low
doses of corticosteroids (if there is a poor
response on corticotropin testing, indicating
adrenocorticoid insufficiency, corticosteroids
should be continued)
 Initiate inotropic agents (dopamine) to maintain
blood pressure (mean arterial pressure, 70-100
mm Hg)
 Initiate crystalloids or albumin (5%) to maintain
adequate fluid balance
 Consider the use of a SwanGanz catheter to
monitor hemodynamic measurements
 Other supportive care
 Initiate nasogastric  Administer
tube feeding of a subcutaneous heparin
standard nutrition as prophylaxis
formula against deep venous
 Initiate prophylaxis thrombosis
with proton-pump  In patients with a
inhibitors body temperature of
 Maintain >40C, use cooling by
normoglycemic state conduction or
(serum glucose level, antipyretic agents
<150 mg per deciliter
Complications during the Clinical Course
and Outcomes
 Waterhouse-Friderichsen
syndrome
 results
from meningitis-associated
septicemia
- hemorrhagic infarction of the adrenal glands
- cutaneous petechiae
- common with menigococcal and
pneumococcal meningitis
 ACUTE FOCAL SUPPURATIVE
INFECTIONS
 Brainabscess
 Subdural Empyema
 Extradural Abscess
 Brain abscess
 may arise from a variety of routes [often
from primary infected site in the heart
(acute bacterial endocarditis), lungs, tooth
decay, bones]
 Strep and Staph are the most common
bacteria
 cerebral abscesses are destructive lesions
 central liquefactive necrosis surrounded by
fibrous cap
- edema in surrounding area
 common sites (in descending order)
- frontal lobe
- parietal lobe
- cerebellum
 present with progressive focal deficits
- signs of  ICP
- CSF under  pressure
- WBC and protein 
- glucose normal
 rupture of abscess can cause ventriculitis,
meningitis and venous sinus thrombosis
 surgery and antibiotics have decreased lethality
to less that 10%
 Subdural Empyema
 bacteria and fungus can spread to
subdural space  subdural empyema
 arachnoid and subarachnoid spaces usually
unaffected
 thrombophlebitis may develop in
bridging veins  venous occlusion and
infarct
 Clinical
 febrile
 headache
 neck stiffness
 untreated may develop lethargy
and coma
 CSF profile similar to abscess
 Extradural Abscess
 commonly associated with osteomyelitis
 usually arise from adjacent site of infection
 sinusitis or a surgical procedure
 when occurring in spinal epidural
space  spinal compression
neurosurgical emergency
Viruses
 Examples of Viruses
 Herpes Simplex Virus
 Pathogenesis
 Depending on the virus, the pathogenesis
consists of a mixture of direct viral
pathology or post-infectious inflammatory
or immune-mediated response
 Acute Aseptic (Viral Meningitis)
 refers to absence of any recognizable
organism
 generally viral
 clinical course is less fulminant
compared to bacterial
 Spinal tab yields
 CSF glucose near normal
 protein only moderately elevated
 lymphocytic pleocytosis
 usually self limiting
 most common is the enterovirus
Drug-induced aseptic meningitis
 NSAID
 antibiotics
 CSF is sterile
 glucose normal (CSF)
 pleocytosis with neutrophils
  CSF protein
 Viral encephalitis
 parenchymal infection
 meningeal inflammation and sometimes spinal cord
involvement (encephalomyelitis)
 most characteristic features
 perivascular and parenchymal mononuclear cell
infiltration
 intrauterine viral infections may cause congenital
malformations (rubella)
 slowly progressive degenerative disease may occur
many years after viral illness
 postencephalitic parkinsonism
 Clinical
 generalized neurologic deficits
- seizures
- confusion
- delirium
- stupor and coma
 CSF usually colorless
- slightly  pressure
- initially a neutrophilic pleocytosis, which rapidly
- converts to lymphocytes
- proteins are 
- glucose is normal
 Herpes virus in CNS
Encephalitis HSV-1/2, VZV, CMV
Acute meningitis HSV-2, VZV
Recurrent meningitis HSV-2
Myelitis HSV-2, VZV, CMV, EBV
Combined EBV
Ventriculitis VZV, CMV
Brainstem encephalitis HSV-1/2, VZV
polymyeloradiculitis CMV
 HSV type 1 (HSV-1)
 occur at any age
 most common in children and young
adults
 most common S & S are mood and
memory change
 most often begins in the temporal lobes
and orbital gyri of frontal lobes
 HSV type 2 (HSV-2)
 in adults as meningitis
 ~ 50% of neonates develop severe
encephalitis to mothers having active
 primary genital HSV infections
Varicella-Zoster virus (Herpes Zoster)
 childhood chickenpox
 reactivation in adults (i.e., “shingles”)
 painful vascular skin eruptions
 usually is self limited, however
 may be a persistent postherpetic neuralgia syndrome
- ~ 10% of patients
 overt CNS manifestations are rare
 however, when present do produce
more severe signs
- granulomatous arteritis
 Cytomegalovirus
 occurs in fetuses and immunosupprressed
 most common opportunistic viral pathogen in
patients with AIDS
 affects 15-20% of patients
 localizein paraventricular subependymal
regions of the brain
 severe hemorrhagic necrotizing
 Clinical
 CMV encephalitis  CMV
 Acute-subacute polyradiculomyelitis
confusion  Sacral pain
 Disorientation paraesthesia
 Memory loss  Sphincter dysfunction
 Cranial n. palsy  Subacute onset of
 Fever ascending flaccid
paraparesis
 CSF
• Hypoglycorrhachia  CSF
• Mononuclear • Hypoglycorrhachia
pleocytosis • PMN pleocytosis
 Diagnosis
 CMV PCR +
 Treatment
 Ganciclovir 5 mg/kg bid 3 wk + foscarnet
60 mg/kg q 8 h until improved
 Maintenance Val-GCV 900 mg OD+
foscarnet 90-120 mg IV OD
TB
 TB
 headaches
 malaise and confusion
 vomiting
 CSF:
 moderate pleocytosis
- PMN and MN
 proteins markedly 
 glucose slightly  or normal
 Subarachnoid space  fibrous exudate
 most often at base of brain
 often obliterating the cisterns
 encasing cranial nerves
 development
of a single intraparenchymal
mass  tuberculoma
 may cause significant mass effect
 Clinical
 most serious is arachnoid fibrosis and
- hydrocepahlus
 obliterative endarteritis
- arterial occlusion and infarction
 spinal cord roots may be involved
 Treatment

2IRZE(S) + 10 IR
 Treatment
 3 IRZS + 6IRZ
 Dexamethasone IV 0.4 MKD 1 wk then 0.3
MKD 1 wk then 0.2 MKD 1 wk then 0.1
MKD 1 wk then oral 4 mg/d tape 1 mg/d
within 4 wk
Spirochete
 Neurosyphilis
 tertiary stage
 ~ 10% of untreated patients
 major forms of meningovascular neurosyphilis are
paretic, and tabes dorsalis
 meningovascular neurosyphilis is chronic meningitis
involving base of the brain, spinal leptomeninges and
cerebral convexities. Obliterative endarteritis (Heubner
arteritis)
 paretic neurosyphilis caused by invasion of the brain by
T. pallidum. Progressive loss of mental and physical
functions with mood alterations
 Tabes dorsalis is a result of damage by the spirochete to
the sensory nerves in dorsal roots, causing locomotor
ataxia and sense of position, loss of pain sensation
 Diagnosis
 CSF reactive FTA-ABS or TPHA
 Treatment
 Penicillin
G IV 4 mU q 4 h 14d then
benzathine penicillin G 2.4 mU IM x3
Fungi
 Example of a Fungus
 Cryptococcus neoformans
 Clinical
 Fever
 Headache
 Stiffness of neck positive
 Sign of increase ICP
 Diagnosis
 Indianink
 Cryptococcal Ag
 Treatment
disease protocal dose duration

HIV neg. 1 Amphotericin 0.7MKD 2 wk

+flucytosine 100MKD
+fluconazole 400mg/d 10 wk
2 Amphotericin 0.7MKD 10 wk
+flucytosine 100MKD
HIV pos. Amphotericin 0.7MKD 2 wk
induction +flucytosine 100MKD
+fluconazole 400mg/d 10 wk
maintanance Fluconazole 400 mg/d
Parasites
 Examples of Parasites
 Toxoplasma gondii
 Clinical
 Subacute t0 chronic fever
 Headache
 Focal neurodeficit correlate with
anatomical site involvement (basal ganglia
and corticomedullary junction)
 Diagnosis
 Definite – tissue biopsy
 Anti-toxplasma IgG
 Clinical compatible+ imaging
 Treatment
 Pyrimethamine 200  Pyrimethamine +
mg then 50-75 mg + folinic acid
sulfadiazine 1-1.5g q  Clindamycin 600 mg q
6 h + folinic acid 15 6h
mg OD at least 6  Azithromycin 900-
weeks 1200 mg OD
 Cotrimoxazole (5
mg/kg TMP) bid
 Secondary prophylaxis
 Pyrimethamine 25-50 mg + sulfadiazine
0.5-1g q 6 h + folinic acid 15 mg OD
 Pyrimethamine 25-50 mg + clindamycin
600 mg q 6 h + folinic acid 15 mg OD
 Stop CD4 > 200 > 6 mo.