CNS infection

Supischa theerasasawat

Content
 

Routs Classification by organ involvement

  

Meningitis Encephalitis Myelitis Bacteria Virus TB Fungus Spirochete Parasite

Classification by pathogen
     

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 Inflammation of the brain itself Caused by many types of organisms Inflammation of the spinal cord

 Encephalitis
 

 Myelitis


Meningitis classified
 acute


pyogenic

usually bacterial meningitis usually acute viral meningitis usually TB, spirochetes, cryptococcus

 aseptic


 chronic


Characteristic CSF formulas

Imaging should precede lumbar puncture

 new-onset new-

seizures  an immunocompromised state  signs that are suspicious for spacespaceoccupying lesions  moderate-to-severe impairment of moderate-toconsciousness

Encephalitis
 Acute

fluflu-like prodome, high fever, severe headache, N/V, altered consciousness, 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% 90%  Fever > 90% 90%  Stiffness of neck > 85% 85%  Vomiting 35% 35%  Seizures 30% 30%  Weakness 15% 15%

Spinal tab yields

 cloudy

or frankly purulent CSF ( 10010,000 WBC)  increased pressure (40% presure >400mmH2O)  o 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 <15 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* Scale*


Airway and respiratory care



Intubate or provide noninvasive ventilation in patients with worsening consciousness (clinical and laboratory indicators for intubation include >35 poor cough and pooling secretions, a RR of >35 per minute, arterial oxygen saturation of <90%) <90% Maintain ventilatory support with intermittent mandatory ventilation, pressure-support pressureventilation, 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 (mean 70mm Hg) Initiate crystalloids or albumin (5%) to maintain (5 adequate fluid balance Consider the use of a SwanGanz catheter to monitor hemodynamic measurements

Other supportive care



Initiate nasogastric tube feeding of a standard nutrition formula Initiate prophylaxis with proton-pump protoninhibitors Maintain normoglycemic state (serum glucose level, <150 mg per deciliter

Administer subcutaneous heparin as prophylaxis against deep venous thrombosis In patients with a body temperature of >40C, use cooling by 40C, conduction or antipyretic agents

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

 Brain

abscess  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 o ICP - CSF under o pressure - WBC and protein o - 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 p subdural empyema  arachnoid and subarachnoid spaces usually unaffected  thrombophlebitis may develop in bridging veins p 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 p 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 postor immune-mediated response immune-

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  o CSF protein

Viral encephalitis


parenchymal infection


meningeal inflammation and sometimes spinal cord involvement (encephalomyelitis) perivascular and parenchymal mononuclear cell infiltration intrauterine viral infections may cause congenital malformations (rubella)

most characteristic features



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 o pressure - initially a neutrophilic pleocytosis, which rapidly - converts to lymphocytes - proteins are o - glucose is normal


Herpes virus in CNS

Encephalitis Acute meningitis Recurrent meningitis Myelitis Combined Ventriculitis Brainstem encephalitis polymyeloradiculitis HSV-1/2, VZV, CMV HSVHSV-2, VZV HSVHSV-2 HSVHSV-2, VZV, CMV, EBV HSVEBV VZV, CMV HSV-1/2, VZV HSVCMV

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

 localize


in paraventricular subependymal regions of the brain

severe hemorrhagic necrotizing

Clinical


CMV encephalitis


    

AcuteAcute-subacute confusion Disorientation Memory loss Cranial n. palsy Fever CSF

Hypoglycorrhachia Mononuclear pleocytosis

CMV polyradiculomyelitis


 

Sacral pain paraesthesia Sphincter dysfunction Subacute onset of ascending flaccid paraparesis CSF
Hypoglycorrhachia 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+ Valfoscarnet 90-120 mg IV OD 90-

TB

TB
 headaches  malaise

and confusion  vomiting  CSF:



moderate pleocytosis

- PMN and MN
 

proteins markedly o glucose slightly q or normal

 Subarachnoid
  

space p fibrous exudate

most often at base of brain often obliterating the cisterns encasing cranial nerves

 development


of a single intraparenchymal mass p 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 FTA-

Treatment
 Penicillin

G IV 4 mU q 4 h 14d then 14d benzathine penicillin G 2.4 mU IM x3 x3

Fungi

Example of a Fungus
 Cryptococcus

neoformans

Clinical
 Fever  Headache  Stiffness

of neck positive  Sign of increase ICP

Diagnosis
 Indian

ink  Cryptococcal Ag

Treatment
disease HIV neg. protocal 1 dose Amphotericin 0.7MKD +flucytosine 100MKD 100MKD +fluconazole 400mg/d 400mg/d Amphotericin 0.7MKD +flucytosine 100MKD 100MKD Amphotericin 0.7MKD +flucytosine 100MKD 100MKD +fluconazole 400mg/d 400mg/d Fluconazole 400 mg/d duration 2 wk 10 wk 10 wk 2 wk 10 wk

2 HIV pos. induction maintanance

Parasites

Examples of Parasites
 Toxoplasma

gondii

Clinical
 Subacute

t0 t0 chronic fever  Headache  Focal neurodeficit correlate with anatomical site involvement (basal ganglia (basal and corticomedullary junction) junction)

Diagnosis
tissue biopsy  Anti-toxplasma IgG Anti Clinical compatible+ imaging
 Definite

Treatment


Pyrimethamine 200 mg then 50-75 mg + 50sulfadiazine 1-1.5g q 6 h + folinic acid 15 mg OD at least 6 weeks

Pyrimethamine + folinic acid



Clindamycin 600 mg q 6h Azithromycin 9009001200 mg OD

Cotrimoxazole (5 (5 mg/kg TMP) bid

Secondary prophylaxis
 Pyrimethamine

25-50 mg + sulfadiazine 250.5-1g q 6 h + folinic acid 15 mg OD  Pyrimethamine 25-50 mg + clindamycin 25600 mg q 6 h + folinic acid 15 mg OD  Stop CD4 > 200 > 6 mo. CD4