Transcript CNS Infections - McGill University
CNS Infections
ELS Wednesday, August 6th 2008 Amal Al-Hashmi
Outline
Viral meningitis Viral encephalitis Bacterial meningitis • Etiology • Pathophysiology • Clinical Presenation • Pathophysiology • Diagnostic tools CT, MRI head, LP,EEG • Treatment
Viral meningitis
Definition an inflammatory response to viral infection of leptomeningeal cells and the subarachnoid space account for the majority, at least 70%, of cases of aseptic meningitis
Etiology
In Europe and US nonpolio enteroviruses are the most common case of viral meningitis ( Kupila et al 2006) for both children & adults (coxsackie & enteric cytopathogenic human orphan virus [echovirus]), are the most common causal agents
Etiology
followed by mumps arboviruses herpesviruses lymphocytic choriomeningitis HIV at the time of seroconversion
Clinical presentation
Children under 2 years of age show fever, irritability, or seizures , but may never develop signs of meningeal irritation Adult pts present with fever, malaise, headache, nausea, vomiting, nuchal rigidity, & photophobia
CSF
1- slightly elevated opening pressure 2- mild to moderate pleocytosis with 10–500 white blood cells (WBC)/µl, predominantly lymphocytes 3- mildly elevated protein (<100 mg/dl), 4- normal glucose
CSF
RT-CRP has now replaced viral cultures as diagnostic procedure of choice for establishing enteroviral infections ( Ramers et al 2000) computed tomography or magnetic resonance imaging (MRI) scans in general are normal
Viral Encephalitis
Etiology C/F CSF findings Neuroimaging
Viral Encephalitis
Most common cause are herpes simplex and arboviruses HSV-1 most common cause of fetal encephalitis in US accounting for 10% overall& 90% in adult frequency 1/250,000 HSV-2 more commonly isolated in monophasic or recurrent meninigitis & congenitally acquired neonatal HSV meningoencephalitis
Viral Encephalitis
C/F Fever 90% Headache 80% Altered mentation 70% Personality changes 70-80% Seizures 40-67% Memory disturbance 25-45% Motor deficit 30-40% Aphaisa 33% Olfactory hallucination
Viral Encephalitis
No set of signs or symptoms is pathognomonic of HSE (Whitly 2006)
CSF
increased opening pressure Normal glucose Moderalty elevated protien Lymphocytic pleocytosis 10 1000/microlitter Xanthochromia and red cells may occur Cultures negative in 95%
CSF
PCR of HSE is the diagnostic procedure of choice ( lakeman & whitely 1995) False negative ( Weil et al. 2002)
Neuroimaging
particularly MRI,may show temporal or orbitofrontal cortex enhancement or edema in HSE ( Raschilas et al 2002) In most other acute viral encephalitis, neuroimaging findings are nonspecific Brain MRI or CT serve to exclude brain abscess, subdural empyema, cranial extradural abscess, or septic venous thrombosis
EEG
Diffuse slowing Focal abnormalities in the temporal region ( 75% with +ve PCR) PLEDS
Brain Biopsy
Atypical cases Poor response to treatment Findings: hemorrahgic necrosis HSV antigen in infected neurons acidophilic intranuclear inclusions
Treatment
Empiric therapy with acyclovir should be started immediately Stander Rx course is IV acyclovir 10mg/kg Q8h in adults 20mg/kg Q8h in neonate and children Duration 14-21 days
Treatment
Steroid ?
Retrospective studies suggested no obvious harm and be some benefit ( Kamie et al 2006) Controlled clinical trails are needed
Prognosis
Mortality rate in untreated cases is 70% which reduced to 19-27% with rx Morbidity remains high only 37% of all pt PCR proven and treated with acyclovir survive with no or mild residual deficits (Raschilas et al2002)
Prognosis
Clinical relapse can occur and more often in children and neonate Consider Foscarnet in cases of acyclovir resistant stains or in who are allergic
Bacterial meningitis
Incidence of 3-5/100 000/year in US (quagliarello 1997) More than 1500 death/yr in US
Etiology - General
Pneumococcus (Streptococcus Pneumoniae) • Most common in adults >20 • Account for ½ of reported cases • 2 ° to pneumonia/otitis, splenectomy/DM2 • ’ing incidence of pen-resistance in pneumococcus (25-45% to pen, 10% to Ceph,+ to chloramphenicol)
Etiology - General
HiB (Haemophilus Influenzae type B) • Before vaccination, most common case in US 45% of meningitis caused by Hib • Now accounts for less than 10%– • still in elderly, HIV pts
Etiology - General
Meningococcus (Neisseria Meningitidis) • Mainly children and young adults (army/college) • 2 ° to asymptomatic nasopharyngeal colonization
Etiology – Special Populations
Neonate • GBS, E. coli & other gram neg., Listeria (10%) Post head trauma/Neurosurgery • Staph Aureus & CNS, Enteric gram neg.
Elderly • Listeria and Hib Listeria = Impaired cellular immunity • Pregnancy, Chronic disease, Elderly, Alcohol
Clinical Presentation
Triad of Headache, fever and neck stiffness: 85% of patients N/V, photophobia, myalgia ( common) Alteration in LOC, Seizures (40%) Nuchal rigidity: resistance to passive flexion Kernig’s: extension of the knee with thigh flexed pain, neck flexion Brudzinsky’s • Flexion of neck causes hip flexion
Clinical Presentation
Cranial nerve palsies 3 rd , 6 th (10-20%) , 7 th Occasionally focal neurological deficit hemiparesis, dysphasia
Clinical Presentation
Classical c/f are commonly absent in neonates look for high pitched crying, refusal to feed, irritability In elderly less act onset of lethrgy, mild or no fever
Certain clinical features
Promient rash particually extrimities (Meningococcus) erythemaous, macular evolving into petechial Rhinorrhea or otorrhea with S pneumoniae
Pathophysiology
Bacteria spread by droplets and colonize nasopharynx bacteremia then meningeal spread thru chroroid plexus epithelial cells Multiply rapidly because of absence of immune cells
Lysis of bacterial cell wall in SAS
Stimulate microglia inflammatory cytokine production of IL-1 and TNF
Roos, seminars in neurology 2000
Pathophysiology
Alteration of BBB w/ vasogenic edema + loss of autoregulation AND entry of PMN w/ cytotoxic edema SO formation of purulent exudate Hydrocephalus narrows arteries in SAS and invades wall (vasculitis; leads to CVA) Continous rise of ICP and coma
CSF
↑ pressure 20-50 mm H20 ↑ WBC (100-10000 wbc/mm3, mainly PMN) ↓ glucose (less than 40% of serum glu) ↑ Protein (1.0-5.0 mg/dl) Positive gram stain/culture in 70 90% • Less if Abx before; sterile only after 12h Bx if skin lesions
Diagnosis
Blood Cultures (50%) Abx before LP if CT/LP delay Tx (no change in WBC +/- in sterility for hours) +/- Decadron CT head (?) Lumbar Puncture
CT Head before LP?
• CT will be abnormal, if you have : Seizure clinical evidence of increased ICP Hx of CNS disease Immuncompromised status Age>60 Abnormal neurological exam (including mental status) Hasbun et al. CT head before LP in suspected meningitis. NEJM 345:1727, 2001 Kastenbauer et al. CT head before LP in suspected meningitis. NEJM 346:1248, 02
CT SCAN PRIOR TO LUMBAR PUNCTURE IN SUSPECTED MENINGITIS
235 patients with suspected meningitis underwent CT 56/235 (24%) had abnormal CT; 11 (5%) with mass effect Hasbun et al. NEJM 2001;345:1727.
CT SCAN PRIOR TO LUMBAR PUNCTURE IN SUSPECTED MENINGITIS
96 patients without above features who underwent CT • 93 had normal CT; 1 had mass effect • All had lumbar puncture with no evidence of brain herniation Hasbun et al. NEJM 2001;345:1727.
CT before LP
• Kastenbauer: Nothing predicts herniation (Abnormal CT in 2/10 herniations and 27/65 w/ no herniation) of Kastenbauer et al. N Engl J Med 2002;346(16):1248-1251. (189K)
Age of patient 0-12 weeks 3 months-50 years >50 years
Treatment
Likely organism Antimicrobial therapy*
Group B Strep E. Coli L. Monocytogenes
3rd generation cephalosporin + ampicillin (+ dexamethasone first 2 days in >4-8-week-old infant)
S. Pneumoniae N. Meningitidis H. Influenzae S. Pneumoniae L. Monocytogenes Gram-neg. bacilli
3rd generation ceph + vancomycin ( ± ampicillin ) 3rd generation ceph + vancomycin + ampicillin Base of skull fracture Immunocompromi sed state
Staphylococci Gram-neg. bacilli S. pneumoniae L. Monocytogenes Gram-neg. bacilli S. Pneumoniae H. Influenzae
3rd generation cephalosporin + vancomycin Vancomycin + ampicillin + ceftazidime
Treatment
Based on age Always bactericidal Consider intrathecal Vanco Alternatives: • Cefepime or meropenem instead of 3rd generation Ceph • If severe Pen allergy: Vanco + chloramphenicol or Vanco + septra (listeria) 3rd generation Cephalosporin • Ceftriaxone 2g q12h – jaundice in neonates • Cefotaxime 2g q4h • Ceftazidime 2g q 8h
Tx of contacts
Contact Public Health for meningococcus and HiB Need to treat close contacts (potentially share secretions) • Rifampin bid for two days C • Or Cipro 500mg once • Or zithromax 500mg once
Prevention
Pneumovax for surgical or functional asplenia (sickle cell, chronic illness, immunosuppression, older age…)
Steroids
Morbidity and mortality of meningitis related of inflammatory reaction rather than bacteria themselves Decadron inhibits IL-1 and TNF m RNA production and CSF outflow resistance and stabilizing BBB Lots of small studies 1950’s-2002; big studies are rare, especially in adults.
Steroid
The available evidence on adjunctive dexamethasone therapy confirms a benefit for treating H influenza type b in reducing audiological sequelae and suggest benefit in reducing the audiological and neurological sequelae in H influenza type b and pneumococcal in children (sebire et al 2006) …….( weisfelt et al 2006)
Cochrane Review 2003
18 RCT Mainly kids General • Lower mortality RR 0.76 [.59-.98] • Hearing loss 0.36 [.22-.60] • Neuro Sequelae 0.66 [.44-.99] In Children • Lower hearing loss in non Hib meningitis 0.42 [.2 - .89] In adults • Lower mortality 0.48 [0.24-0.96]
Systematic Review in adults
5 RCT in adults • Overall mortality and neuro sequelae 0.6
• Pneumococcus mortality 0.5
• Meningococcal sequelae 0.5 and mortality 0.9
No increased side effects with steroids
Vanco level controversy
Experimental evidence of decreased absorption if steroids given One RCT study in children demonstarted reliable penetration of vanco if 60mg/kg doses used.
4/11 pts in adults failed vanco with steroids but used lower dosages
Steroids
Do not use if immunosuppressed