meningitis and encephalitis
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Meningitis and Meningitis and Encephalitis Encephalitis
Department of Emergency Medicine and Forensic
Khon Kaen Hospital
DR.P ornlert Pluemchitmongkhon
Meningitis
• Inflammation of the membranes of the brain or spinal cord
Encephalitis
• Inflammation of the brain parenchyma, presents as diffuse and/or focal neuropsychological dysfunction
• Most commonly a viral infection with parenchymal damage varying from mild to profound
Epidemiology
• Bacterial meningitis is a common disease worldwide.
• 5-10 per 100,000 people per year in USA.
• Men are affected more than women.• Meningococcal meningitis is endemic
in parts of Africa.• The incidence of viral meningitis ~ 11-
27 per 100,000 people
Etiology
• Meningeal infection associated with a dural leak secondary to neurosurgery or neurotrauma – S.pneumoniae, Staphylococcus aureus, P.aeruginosa, coliform bacteria.
• Viral meningitis- Enteroviruses are statistically most commonly -Causes of “nonparalytic polio”
• Fungal and parasitic meningitides – immunocompromised.
Etiology-meningitis
Viral Etiologies
Causes in Thailand
• Virus–Arbovirus : JEV & Dengue virus–Herpes virus (simplex , zoster) –Enteroviruses including coxsackie
virus, poliovirus, and echovirus–Other causes include varicella
(chickenpox), measles, mumps, rubella, adenovirus, rabies
Etiology-encephalitis
• Arboviruses and herpes simplex virus, HHV are the most common causes of endemic and sporadic cases of encephalitis, respectively.
• Varicella, herpes zoster, HHV 6 and 7, and Epstein-Barr virus - cause of encephalitis in immunocompetent hosts.
• Severe and Fatal Encephalitis-Arthropod-borne viruses and Herpes simplex viruses
Viruses and Severity of Disease
Seasonal Distribution
Noninfectious meningitides
Pathophysiology
Bacterial Meningitis1.Nasopharyngeal colonization and
mucosal invasion 2.Evasion of the complement pathway3.Bacterial cross the BBB to CSF
Bacterial Meningitis
• Mechanism of invasion is not completely understood.
• Host defense mechanism within the CSF are often ineffective.
• Bacterial proliferation stimulate a convergence of leukocyte into the CSF.
• Meningeal and subarachnoid space inflammation release of cytokines into the CSF ( TNF, interleukin 1,6 )
Viral Meningitis and Encephalitis
Herpes Simplex Virus
Viral Meningitis and Encephalitis
Viral replication• Hematogenous spread to CNS• Retrograde transmission along
neuronal axon• Direct invasion of the subarachnoid
space หลั�งจาก infection ของ olfactory submucosa
Eastern Encephalitis Virus
Equine Death from Viral Encephalitis
Regions Reporting Japanese Encephalitis
Encephalitis morbidity and mortality, Thailand 1976-2005
อ�ตราป่ วยของโรค Encephalitis unspecified (ต�อ แสนป่ระชากร ) จ�าแนกตามกลั��มอาย� ป่� พ.ศ .
2545 - 2549
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
2002 2003 2004 2005 2006
0-4
5-9.00
10-14.00
15+
อ�ตราป่ วยของโรค Japanese Encephalitis B (ต�อ แสนป่ระชากร ) จ�าแนกตามกลั��มอาย� ป่� พ.ศ .
2545 - 2549
00.10.20.30.40.50.60.70.8
2002 2003 2004 2005 2006
0-4
5-9
10-14
15-24
25-34
35+
Japanese B Encephalitis morbidity and mortality, Thailand 1976-2005
History of Japanese Encephalitis
• 1800s – recognized in Japan• 1924 – Japan epidemic. 6125 cases, 3797 deaths• 1935 – virus isolated in brain of Japanese patient
who died of encephalitis• 1938 – virus isolated from Culex mosquitoes in
Japan• 1948 – Japan outbreak• 1949 – Korea outbreak• 1966 – China outbreak• Today – extremely prevalent in South East Asia
30,000-50,000 cases reported each year
Japanese Encephalitis Most important cause of
arboviral encephalitis worldwide, with over 45,000 cases reported annually
Transmitted by culex mosquito, which breeds in rice fields› Mosquitoes become
infected by feeding on domestic pigs and wild birds infected with Japanese encephalitis virus
› Infected mosquitoes transmit virus to humans and animals during the feeding process
Encephalitis and Japanese Encephalitis situation by Province
2006
Rice Fields
Japanese Encephalitis Virus
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ป่ระช�ม
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ทางระบบทางเดี+น หายใจ ระบบทางเดี+นอาหาร ต�บ ม!าม ต�อมน�,าเหลั&องโต เป่7นต!น
32 ระบ�ต�าแหน�งของความผู้+ดีป่กต+ในระบบป่ระสาท - CSF space (เย&)อห�!มสมอง-meningitis) ไม�ม%ความผู้+ดีป่กต+ใน
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แลัะ peripheral nerve (radiculoneuropathy) 33. ตรวจร�างกายทางระบบป่ระสาท
4.ป่ระเม�นคำวิ�มเส !ยงข้องก�รเจ�ะน�$�ไข้ส�นหล�ง
Clinical FeaturesSymptoms and Signs• Classical CNS infection - Fever,
Headache, photophobia, nuchal rigidity, lethargy, malaise, altered sensorium, seizure, vomiting, chill
• Immunosuppressed and geriatric pt. → diagnostic challenge
• Often, the only presenting sign of meningitis in the elderly pt. is an alteration of mental status
• Some degree of fever is present in most pt.
Clinical Features
The physical finding• Vary• Depending on the host, causative
organism, severity of the illness• Kernig’s and Brudzinski’s signs are
present ~ 50 % of adults.• DTR may be ↑.• Ophthalmoplegia may be present →
lateral rectus muscle
Clinical Features
The systemic finding• Sinusitis, otitis media, mastoiditis,
pneumonia, UTI, endocarditis, arthritis
• Petechiae, cutaneous hemorrhage
Clinical Features
• Focal neuro deficit and seizure : more commonly with encephalitis than meningitis.
• HSV encephalitis → Dysphasia, seizure.
• WNV → produce myelitis → flaccid paralysis, clear sensorium เหม&อนก�บ Guillian-Barre’ Syndrome แลัะ polio.
Complication of Bacterial meningitis
Complication of Bacterial meningitis
Bacterial Meningitis• Fatality rate for pneumococcal meningitis ~
20-25%.• Higher fatality rate → serious underlying,
concomitant disease, advance age• Prognosis → related to degree of neuro
impairment on presentation• 20-30% of pneumococcal meningitis → residual
neuro deficit.• 40% fatality rate for Listeria meningitis.• ATB → ↓mortality from meningococcal
meningitis ไดี!เหลั&อ < 20%• Mortality rate in community-acquired G-ve
meningitis < 20% เม&)อเร+)มให! 3rd gen cephalosporin.
Viral meningitis
• Various complication related to the systemic effect - orchitis, parotitis, pancreatitis
• Usually all of these complication resolve without sequelae.
Viral Encephalitis
• The outcome dependent on in infecting agent.
• HSV encephalitis → 60-70% mortality( before use acyclovir Tx )
→ 30% ( Acyclovir Tx )
• Common sequelae → seizure, motor deficit, change in mentation.
TB meningitis
• Death in adult age 10-50% ( pt.age, duration of symptom before presentation)
• Focal ischemic stroke → result from cerebral vasculitis.
• 25% of pt. → required neurosurgical procedure ( VP shunt or drainage).
Fungal meningitis
• Abscess, papilledema, neuro deficit, seizure, bone invasion, fluid collection direct invasion of the optic n. → ocular abn. 40% in cryptococcal meningitis.
Diagnostic StrategiesDiagnostic Strategies
Diagnostic StrategiesDiagnostic Strategies
Lumbar Puncture
Contraindication • Present of infection in the skin, soft
tissue at the puncture site.• Likelihood of brain herniation.
Contraindication • Present of infection in the skin, soft
tissue at the puncture site.• Likelihood of brain herniation.
Lumbar PunctureIndication for CT scan before LP in suspected Bacterial meningitis
• Immunocompromised state
• History of Stroke
Mass lesionFocal infectionHead trauma
• Seizure within last 7 days
• Abnormal level of consciousness
• Inability to answer question or follow command appropiately
• Abnormal visual fields or paresis of gaze
• Focal weakness• Abnormal speech
CSF AnalysisCSF Analysis
Opening pressure- 50-200 mmH2O- Lateral recumbent position and sitting position may increase several fold.- Elevated in bacterial, TB, fungal.- Falsely elevated in tense,
obese, marked muscle contraction.
Collection of Fluid
• At least 3 specimens (1.0-1.5 cc./spec)
• Immediated analysis of turbidity, xanthochromia, glucose, protein, cell count & diff., Gram’s stain, bacterial culture, india ink, AFB, VDRL
• ถึ!าไดี! CSF เลั#กน!อย ส�ง cell count & diff., Gram’s stain, bacterial culture.
Turbidity
• Completely clear, colorless.• Leukocytosis is the most common
cause of CSF turbidity ( > 200 cell/mm3 )
Cell count and diff.
• < 5 WBC /mm3
• < 1 PMN /mm3
• < 1 Eosinophil /mm3
• Pretreatment with few doses of ATB → diminishing the yield of Gram’s stain, bacterial culture, not affect CSF cell count.
• Initial CSF analysis → lymphocytosis 6-13% in bacterial meningitis
• Viral meningitis and encephalitis → usually less than 500 cell/mm3 (nearly 100% mononuclear)
Cell count and diff.
• Early in viral infection < 48 hr. → PMN pleocytosis.
• Normal cell count&diff. → reassure, do not absolutely exclude bacterial meningitis.
• น�$�ไข้ส�นหล�ง อ�จไม"พบ cell เลยใน rabies, dengue, West Nile virus, herpes simplex virus, Nipah virus หร,อ ในกรณี ต้�$งน�$�ไข้ส�นหล�งที่�$งไวิ�น�นเก�นกวิ"� 2 ชี้ม . เน,!องจ�ก 50% ข้องเม.ดเล,อดข้�วิ neutrophils จะสล�ยไป่ที่ !ระยะเวิล�น $
Traumatic LP
• Presense of a clot• Decrease RBC count from tube 1 to 3 • True CSF WBC = measure CSF WBC CSF RBC x Blood WBC Blood RBC• CSF from traumatic LP → 1 WBC / 700
RBC
Gram’s stain• Diminished 20-30% ใน prior treatment with ATB
Pathogen Typical characteristics
StaphylococcusG + cocci: single,double,tetrad,cluster
Streptococcus pneumoniae G + cocci; paired diplococci
Listeria monocytogenes G + rods: single or chain
Neisseria meningitidisG – cocci: paired diplococci;kidney or coffee bean
Haemophilus influenzae G – coccobacilli;pleomorphic
Enterobacteriaceae G – rods
Pseudomonas aeruginosa G – rods
Xanthrochromia
• Lysis of RBC and release of breakdown pigments, oxyhemoglobin, bilirubin and methemoglobin into the CSF.
• Begin within 2 hr. → persist up to 30 days.
• Traumatic tap → ↑ CSF protein 150mg/dl or more
• Subarachnoid hemorrhage.
Glucose
• 50-80 mg/dl• CSF glucose: serum glucose = 0.6:1• Abnormal CSF to serum glucose ratio
< 0.5 in normoglycemic or 0.3 in hyperglycemic
impaired glucose transport mechanism
increase CNS glucose use( pyogenic meningitis )
Glucose
• Mild decrease CSF glucose level --> viral, parameningeal
process.• Bacterial or fungal meningitis →
“hypoglycorrhachia”• ถึ!าระดี�บ serum glucose เพ+)มข(,นอย�าง
รวดีเร#ว เช�น การให! 50% glucose อาจจะใช!เวลัา 4 ช�)วโมงในการป่ร�บสมดี�ลัใน CSF
Protein• 15-45 mg/dl• Traumatic LP
corrected 1 mg/dl of prot./1000 RBC• Elevated CSF protein
→ usually higher than 150mg/dl
Meningitis CNS vasculitisSAH Viral encephalitisSyphilis Demyelination symdromeNeoplasm
>1000 mg/dl → suggest fungal disease
India Ink Preparation
• Cryptococcal disease พบ 1/3 of cases
• More definitive diagnostic test is cryptococcal Antigen.
Lactic Acid
• Nonspecific• >35 mg/dl → bacterial meningitis• <35 mg/dl → normal, viral
meningitis
Antigen Detection CIE ( counterimmunoelectrophoresis) latex agglutination Coagglutination• Useful in receiving ATB before CSF sampling• Result - vary• Presense only an antigen, not viable organism• PCR → HSV sensitivity 95-100% specificity 100% • ระยะเวลัาท%)เหมาะสมในการส�งตรวจน�,าไขส�นหลั�งส�าหร�บไวร�ส HSV
ค&อ ภายในว�นท%) - 3 10 หลั�งจากท%)เร+)มม%อาการแสดีงทางระบบป่ระสาท
• ถึ!าผู้ !ป่ วยไดี!ร�บยาต!านไวร�ส เช�น acyclovir เป่7นเวลัานานมากกว�า 5-7 ว�น อาจท�าให! กรวดีน�,าไขส�นหลั�งไม�พบเช&,อไดี!
Antigen Detection
• Bacteriologic culture → N.meningitis 37-55%→ H.influenzae 50%
• PCR → at least as sensitive as culture technique in detect cryptococcal meningitis.
• PCR → resumed for less clear presentation , pretreat with ATB, care in which concern exists for TB, cryptococcal, treatable viral CNS infection.
Antigen Detection
• PCR → TB sensitivity 80-85% specificity 97-100%
• Sensitivities of detection in CSF by PCR for N.meningitidis 88%, H.influenzae 100%, S.pneumoniae 92% (nearly 100% specificity)
Neuroimaging Technique
• Possibility of an intracranial abscess, ICH, mass lesion
• CT scan should not unnecessarily delay LP or ATB
• Hypodensity CT scan in the temporal lobes → HSV encephilitis
TB or Crypto meningeal involvement
MRI in HSV
Sporadic Herpes Simplex EncephalitisFulminant hemorrhagic and necrotizing
meningoencephalitis
Additional Investigation
• CBC may show leukopenia in elderly, immunosuppressed person.
• Blood culture → identify causative organism more often when the meningitis is caused by pneumococcus than meningococcus
• 50% of pt. with pneumococcal meningitis → evidence of pneumonia on an initial CxR.
• EEG → focal or lateralized EEG abn. → associated with HSV type 1 encephalitis( strong evidence)
Differential Consideration
• Three clinical symptom Acute , subacute, chronic meningitisAcute meningitis < 24 hr., rapidly deteriorate most likely pathogen
S.pneumoniae N.meningitidis H.influenzae
Differential Consideration
• Subacute meningitis 1-7 day viral meningitis, most of bact.&
some of fungal fever + mental status change หา
disease อ&)น นอก CNS เช�น pneumonia, UTI
Differential ConsiderationChronic meningitis
TB meningitis Fungal CNS infection Tertiary syphilis CNS neoplasm Lupus cerebritis Sarcoidosis Rheumatoid arthritis
Granulomatous angiitis Various encephalitides Toxic encephalopathies Metabolic
encephalopathies Multiple sclerosis Chronic subdural
hematoma
Differential ConsiderationChronic meningitis
TB meningitis Fungal CNS infection Tertiary syphilis CNS neoplasm Lupus cerebritis Sarcoidosis Rheumatoid arthritis
Granulomatous angiitis Various encephalitides Toxic encephalopathies Metabolic
encephalopathies Multiple sclerosis Chronic subdural
hematoma
ManagementManagement
Prehospital care
• Field stabilization + transport• Vital sign, Oxygen, alter mental
status, seizure
Assessment and stabilization
• Aggresssive management in septic shock, hypoxemia, seizure, cerebral edema, hypotension from dehydration
• Preexisting condition may complicated the pt. dz. - Recent neurosurgery, trauma, leukopenia, immunocompromised, DM.
• Acute cerebral edema or increase ICP → immediate intubation and adequate ventilation +- osmotic agent (mannitol, diuretic)
Assessment and stabilization
• Aggresssive management in septic shock, hypoxemia, seizure, cerebral edema, hypotension from dehydration
• Preexisting condition may complicated the pt. dz. - Recent neurosurgery, trauma, leukopenia, immunocompromised, DM.
• Acute cerebral edema or increase ICP → immediate intubation and adequate ventilation +- osmotic agent (mannitol,diuretic)
Definitive Therapy
Bacterial meningitis
Empirical ATB for Bacterial meningitis
ATB for bacterial meningitis from Gram’s stain or Culture
ระยะเวลัาในการให!ยาป่ฏิ+ช%วนะใน Bacterial meningitis
Bacterial meningitis• Corticosteroid → additionally recommend in
acute bacterial meningitis.• In animal study – pneumococcal meningitis →
ลัดี brain edema, CSF pressure, CSF lactate level
• Dexamethasone + Cefuroxime or ceftriaxone → ↓ long term hearing loss in infants &
children.• Absolute risk reduction of 10% in adult →
Dexamethasone is given either 15 min before or concomitantly with ATB and continued for 4 days at 6 hr intervals. (greatest in S.pneumoniae.)
• No benefit in N.meningitidis
Viral meningitis
• Short, benign, self-limited course• Complete recovery• Repeated LP in 8-12 hr.
Viral encephalitis
• IV acyclovir 10 mg/kg every 8 hr.• Ganciclovir, foscarnet, ciclofovir →
effective in HHV infection• Pleonaril → effective in enteroviral dz.
TB meningitis
• Corticosteroid decrease secondary complication
Fungal meningitis
• 4 agents are commonly used
Amphotericin BFluconazole MiconazoleFlucytosine
Chemoprophylaxis
• Incidence of transmissionof meningococcus is ~ 5%
• Household contact Rifampin adult 600 mg
child > 1 mo 10mg/kg child < 1 mo 5mg/kg
oral q 12 hr. for a total of 4 doses.• Health care worker → do not required
prophylaxis
Chemoprophylaxis
• Directed contact ( mouth to mouth, ET tube, nasotrachial suction)
Ciprofloxacin 500 mg oral or Ceftriaxone 250 mg im.
( <15 yr. 125 mg im.)• No indication for chemoprophylaxis
in pneumococcal meningitis
Immunoprophylaxis
• Vaccination is also available to confer immune protection against JE virus
• H.influenzae type B vaccine use in pediatrics.
Important !
• Rule out non-viral causes that require specific treatment
• Do not miss herpes simplex encephalitis, which has highly effective treatment
END
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