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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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.

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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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