INFECTIONS OF THE INFECTIONS OF THE CENTRAL NERVOUS SYSTEMCENTRAL NERVOUS SYSTEMCENTRAL NERVOUS SYSTEMCENTRAL NERVOUS SYSTEM

Dr. Kiking Ritarwan, SpS, MKTDr. Kiking Ritarwan, SpS, MKTDepartement of Neurology Medical Departement of Neurology Medical Faculty of University of Sumatera Faculty of University of Sumatera

UtUtUtaraUtara

CNS INFECTIONCNS INFECTIONCNS INFECTIONCNS INFECTIONMENINGITISMENINGITIS-- Inflamation of the meningeal covering of Inflamation of the meningeal covering of Brain and spinal cord.Brain and spinal cord.LEPTOMENINGITIS ( h id i )LEPTOMENINGITIS ( h id i )-- LEPTOMENINGITIS (arachnoid + pia)LEPTOMENINGITIS (arachnoid + pia)PACHYMENINGITIS (duramater)PACHYMENINGITIS (duramater)TYPE OF MENINGITIS : Bacterial TB ViralTYPE OF MENINGITIS : Bacterial TB Viral-- TYPE OF MENINGITIS : Bacterial, TB, Viral, TYPE OF MENINGITIS : Bacterial, TB, Viral, fungal.fungal.

ENCEPHALITISENCEPHALITISMYELITISMYELITIS

Acute Pyogenic MeningitisAcute Pyogenic Meningitis= Bacterial meningitis= Bacterial meningitis= Bacterial meningitis= Bacterial meningitis

Is an inflamatory response to bacterial infections Is an inflamatory response to bacterial infections involving the pia and arachnoid membrane coveringinvolving the pia and arachnoid membrane coveringinvolving the pia and arachnoid membrane covering involving the pia and arachnoid membrane covering the brain and spinal cord.the brain and spinal cord.Many org. can produce pyogenic meningitisMany org. can produce pyogenic meningitisMany org. can produce pyogenic meningitisMany org. can produce pyogenic meningitisIt can be categorised into:It can be categorised into:a. Spontaneous community acquired meningitisa. Spontaneous community acquired meningitisp y q gp y q gb. Post traumatic meningitis following neurosurb. Post traumatic meningitis following neurosur--

gery or fx of the skull.gery or fx of the skull.g yg yc. Device associated meningitis particularly in assoc. c. Device associated meningitis particularly in assoc.

With CSF Shunts and drain.With CSF Shunts and drain.

The causative org. of meningitis can be The causative org. of meningitis can be predicted based on the patient’s age, exposure predicted based on the patient’s age, exposure to an epidemic, vacc. Against common agents to an epidemic, vacc. Against common agents (eg. (eg. H. Influenza, Streptococcus pneumonie, N. H. Influenza, Streptococcus pneumonie, N. meningitidismeningitidis) and Immune state.) and Immune state.

Pathology is characterized by inflammation of Pathology is characterized by inflammation of the meninges and cortical blood vesselsthe meninges and cortical blood vesselsthe meninges and cortical blood vessels.the meninges and cortical blood vessels.

Etiology of Bacterial meningitisEtiology of Bacterial meningitisEtiology of Bacterial meningitisEtiology of Bacterial meningitisAge Microorg.Age Microorg.g gg g

-- Neonate ( 0Neonate ( 0--2 bln) Streptococ group B, E coli, list.2 bln) Streptococ group B, E coli, list.Stap. Aureus, Enterobacter,Stap. Aureus, Enterobacter,P d H filP d H filPseudomonas, HaemofilusPseudomonas, Haemofilus

-- Child S. pneumonie, N. meningitidis,Child S. pneumonie, N. meningitidis,H. influenzae.H. influenzae.H. influenzae.H. influenzae.

-- Youth ( 6Youth ( 6--2020thth) N. meningitidis, S. pneumonie,H. infl.) N. meningitidis, S. pneumonie,H. infl.-- Adult ( > 20 thn) S. pneu, N. meningi, Streptococ,Staph.Adult ( > 20 thn) S. pneu, N. meningi, Streptococ,Staph.

Clinical PictureClinical PictureTh diti ll i b thTh diti ll i b thThe conditions occurs equally in both sexesThe conditions occurs equally in both sexesChildren aged 6 month to 1 year are at the greatest Children aged 6 month to 1 year are at the greatest risk and children under 15 years of age comprise 75%risk and children under 15 years of age comprise 75%risk and children under 15 years of age comprise 75% risk and children under 15 years of age comprise 75% of all cases. Patients aged 60 and older may be of all cases. Patients aged 60 and older may be atypical.atypical.Symptoms and signsSymptoms and signsSymptoms and signsSymptoms and signsI. early infection: fever, headache, malaise,vomiteI. early infection: fever, headache, malaise,vomiteII Higher ICP: vomite headache seizure alteration ofII Higher ICP: vomite headache seizure alteration ofII. Higher ICP: vomite, headache, seizure, alteration of II. Higher ICP: vomite, headache, seizure, alteration of

consciousness, papiledemaconsciousness, papiledemaIII. Meningeal irritation: nuchal rigidity, Kernig and III. Meningeal irritation: nuchal rigidity, Kernig and

Brudzinski +Brudzinski +IV. CSF:neutrophilic pleocytosis, low glucose level, IV. CSF:neutrophilic pleocytosis, low glucose level,

l t d t i t til t d t i t tielevated protein concentrationelevated protein concentration

CSF FindingsCSF FindingsCSF FindingsCSF Findings

CSF Parameter Bacterial meningitisCSF Parameter Bacterial meningitisCSF Parameter Bacterial meningitisCSF Parameter Bacterial meningitis•• WBC Count > 2000/ ul, >60% PMNWBC Count > 2000/ ul, >60% PMN

Gl 40 / dlGl 40 / dl•• Glucose < 40 mg/ dlGlucose < 40 mg/ dl•• Protein > 200 mg/ dlProtein > 200 mg/ dl•• Gram stain + 80%Gram stain + 80%•• Culture + > 90%Culture + > 90%Culture + > 90%Culture + > 90%

Diagnostic ProsedureDiagnostic ProsedureDiagnostic ProsedureDiagnostic ProsedureLumbal PunctureLumbal PunctureBlood should be drawn for blood culture before Blood should be drawn for blood culture before administration of antibiotic.administration of antibiotic.Bacterial antigenBacterial antigenChest, skull mastoid and paranasal sinus x raysChest, skull mastoid and paranasal sinus x raysMRI or CT MRI or CT Neuroimaging shoul be performed before LP in Neuroimaging shoul be performed before LP in the following settings:60 yo or older Depressedthe following settings:60 yo or older Depressedthe following settings:60 yo or older, Depressed the following settings:60 yo or older, Depressed LOC, Focal neurologic signs, papilledema, LOC, Focal neurologic signs, papilledema, Patients is immunocompromised.Patients is immunocompromised.pp

TreatmentTreatment1.Antibiotic therapy should be administrated. A minimum of 2 1.Antibiotic therapy should be administrated. A minimum of 2

weeks of therapy is recommended.weeks of therapy is recommended.Age AntibioticAge Antibioticgg0 0 –– 4 mgg Cefotaxim + Ampi4 mgg Cefotaxim + Ampi44--12 mgg Gen III. Cephalos+ Ampi12 mgg Gen III. Cephalos+ Ampi3 bln3 bln-- 18 thn Gen III Ceph + Ampi atau18 thn Gen III Ceph + Ampi atau3 bln3 bln-- 18 thn Gen III. Ceph + Ampi atau18 thn Gen III. Ceph + Ampi atau

Ampi + chloramph.Ampi + chloramph.18 thn 18 thn –– 50 thn Gen III. Ceph + Ampi50 thn Gen III. Ceph + Ampi50 th G III C h i50 th G III C h i50 thn Gen III. Ceph + ampi.50 thn Gen III. Ceph + ampi.

2. When possible etiologies for meningitis include H. Influenza or 2. When possible etiologies for meningitis include H. Influenza or p g gp g gS Pneumoniae in child, or S Pneumoniae in adults, give S Pneumoniae in child, or S Pneumoniae in adults, give dexamethasone 0,15 mg/kg (IV) every 6 hours for 2dexamethasone 0,15 mg/kg (IV) every 6 hours for 2--4 days in 4 days in child and 10 mg IV every 6 hours for 4 days in adults.child and 10 mg IV every 6 hours for 4 days in adults.

Complication Bacterial meningitisComplication Bacterial meningitisComplication Bacterial meningitisComplication Bacterial meningitis

Cerebral abscessCerebral abscessCerebral abscessCerebral abscessEmpyema subduralEmpyema subduralC l iC l iConvulsieConvulsieShock septicShock septicCerebral edemaCerebral edemaInfarck serebralInfarck serebralInfarck serebralInfarck serebralHerniationHerniation

Sequele bacterial meningitisSequele bacterial meningitisSequele bacterial meningitisSequele bacterial meningitis

Mental retardationMental retardationMental retardationMental retardationHydrocephalusHydrocephalusC l i ikC l i ikConvulsie, psikoseConvulsie, psikoseParese, deafness, blind.Parese, deafness, blind.

Tuberculous meningitisTuberculous meningitisThe first clinical description of tuberculous meningitisin the late 18th Century is credited to the Scottish physiologist Sir Robert Whytt even before Robert Koch isolatedSir Robert Whytt , even before Robert Koch isolated mycobacterium tuberculosis in 1882.Almost 40 years later, Rich and McCordock demonstrate the presence of minute caseous tubercles known as “Rich-foci”presence of minute caseous tubercles known as Rich-foci within the brain or meninges, which formed the basis for understanding the pathogenesis of CNS tuberculosis.

Tuberculosis of the central nervous system (CNS) is the most serious complication of tuberculosis, especially in children.

TB TB hematogenous spread hematogenous spread infection to the brain infection to the brain parenchyma or meninges.parenchyma or meninges.

TB meningitis (TBM)TB meningitis (TBM)TB meningitis (TBM)TB meningitis (TBM)

Definition:Definition:Definition:Definition:TBM is an infection of the meninges caused by TBM is an infection of the meninges caused by the acidthe acid--fast bacillusfast bacillus MycobacteriumMycobacteriumthe acidthe acid fast bacillus fast bacillus Mycobacterium Mycobacterium tuberculosis.tuberculosis.In the west country,the first make not muchIn the west country,the first make not muchIn the west country,the first make not much In the west country,the first make not much difference again, but lately incident mount difference again, but lately incident mount drastically in all the world.drastically in all the world.yyTBM happened at all of age.TBM happened at all of age.Before important HIV factor in prevalens is ageBefore important HIV factor in prevalens is ageBefore important HIV factor in prevalens is ageBefore important HIV factor in prevalens is age

++ 1 7 milyar people ( 1/3 worldwide1 7 milyar people ( 1/3 worldwide++ 1,7 milyar people ( 1/3 worldwide 1,7 milyar people ( 1/3 worldwide people) people) Mycobacterium tuberculosa Mycobacterium tuberculosa infectedinfectedinfected.infected.Reported CDC 2002 was 5,36 cases per Reported CDC 2002 was 5,36 cases per 100 000 people but worldwide the100 000 people but worldwide the100.000 people, but worldwide the 100.000 people, but worldwide the infection rate is much higher.infection rate is much higher.TB i I d i 3TB i I d i 3 dd k f 22k f 22TB in Indonesian occupy 3TB in Indonesian occupy 3rdrd rank from 22 rank from 22 high burden countries.high burden countries.

Indonesia Indonesia 22 High Burden Countries22 High Burden Countries

Indonesia Indonesia 22 High Burden Countries22 High Burden Countries22 High Burden Countries22 High Burden Countries22 High Burden Countries22 High Burden Countries

1. India2. China

3. Indonesia4. Bangladesh5. Nigeria6 P ki t6. Pakistan7. South Africa8. Philippines9. Russia10. Ethiopiap11. Kenya12. DR Congo13. Viet Nam14. UR Tanzania15 Brazil

Indonesia 10%Indonesia 10%Indonesia 10%Indonesia 10%Bangladesh 4%

China15%

China15%

15. Brazil16. Thailand17. Zimbabwe18. Cambodia19. Myanmar

India30%India30%

Philippines 3%

Pakistan 4%

Nigeria 3%

20. Uganda21. Afghanistan22. Mozambique

Other28%

South Africa 2%Russia 1%

3% of All Deaths in Developed 3% of All Deaths in Developed Countries Are Due to TuberculosisCountries Are Due to TuberculosisCountries Are Due to TuberculosisCountries Are Due to Tuberculosis

Diarrheal diseaseTuberculosis Malaria

OthOth

Chronic obstructive Chronic obstructive pulmonary disease 5%pulmonary disease 5%

Perinatal causes3%3%3%3%

4%4%

2%2%

OtherOther27%27%

Respiratory tractRespiratory tractinfection 7%infection 7%

HIV/AIDS 5%HIV/AIDS 5%

Cancer Cancer StrokeStroke

InjuryInjury9%9%

infection 7%infection 7%

Coronary heartCoronary heartdiseasedisease

13%13%

HIV/AIDS h i d fi i i / i d i d fi i d

12%12%StrokeStroke10%10%

HIV/AIDS = human immunodeficiency virus/acquired immunodeficiency syndrome.

Adapted with permission from MacKay J, Mensah GA. The Atlas of Heart Disease and Stroke.Available at: http://www.who.int/cardiovascular_diseases/en/cvd_atlas_16_death_from_stroke.pdf Accessed February 27, 2006.

EtiologiEtiologiMycobacterium tuberculosisMycobacterium tuberculosisgol ordo Actinomycetales familigol ordo Actinomycetales familigol ordo Actinomycetales, familigol ordo Actinomycetales, familiMycobacteriaceae, genus Mycobacteriaceae, genus MycobacteriumMycobacteriumMycobacteriumMycobacteriumSifat : aerob, spora (Sifat : aerob, spora (--), motil (), motil (--), ), berkembang biak lambatberkembang biak lambatberkembang biak lambatberkembang biak lambatMati dgn pemanasan & sinar UVMati dgn pemanasan & sinar UVBakteri batang tahan asam dgnBakteri batang tahan asam dgnBakteri batang tahan asam dgn Bakteri batang tahan asam dgn pewarnaan Ziehlpewarnaan Ziehl––Neelsen Neelsen /Auramin /Auramin leading to nickname leading to nickname gg“ red snapper”.“ red snapper”.

Size :0,3Size :0,3--,0,6 to 1,0,6 to 1--4 um4 umShape:Shape: Rods straight orRods straight orShape: Shape: Rods, straight or Rods, straight or slightly curved, occurring slightly curved, occurring singly or in occasionalsingly or in occasionalsingly or in occasional singly or in occasional threads threads Temperature: 33Temperature: 33 3939oo CCTemperature: 33Temperature: 33--3939oo CCpH 6,6pH 6,6--6,86,8

PATHOLOGYPATHOLOGYPATHOLOGYPATHOLOGY

Aerosol transmission of TuberculosisAerosol transmission of TuberculosisTuberculosis is spread by droplet nuclei which are expelled when a person with infectious TB coughs, sneezes, speaks, or sings

PathologyPathologyTBM is always secondary to TB elsewhere in the TBM is always secondary to TB elsewhere in the body. The primary focus of infection is usually in the body. The primary focus of infection is usually in the l b t b i th l h l d b ll b t b i th l h l d b llungs but may be in the lymph glands, bones, nasal lungs but may be in the lymph glands, bones, nasal sinuses, GIT, or any organ in the body.sinuses, GIT, or any organ in the body.The bacilli usually enter the body byThe bacilli usually enter the body by inhalationinhalationThe bacilli usually enter the body by The bacilli usually enter the body by inhalationinhalation. . Transmission through the skin or by ingestion are rare Transmission through the skin or by ingestion are rare cause of infectioncause of infectioncause of infection.cause of infection.The organisms undergo The organisms undergo multiflication and multiflication and hematogenous disseminationhematogenous dissemination and it is during this and it is during this gg ggstage that the meninges are most likely to become stage that the meninges are most likely to become involved.involved.

Cell mediated immunityCell mediated immunity with migration ofwith migration ofCell mediated immunityCell mediated immunity with migration of with migration of macrophages at the site of infection leads macrophages at the site of infection leads to the development of tuberclesto the development of tuberclesto the development of tubercles.to the development of tubercles.When the immune response fails, the When the immune response fails, the subarachnoid space is infected by rupturesubarachnoid space is infected by rupturesubarachnoid space is infected by rupture subarachnoid space is infected by rupture of meningel tuberclesof meningel tubercles followed by release followed by release of bacilli and the development ofof bacilli and the development ofof bacilli and the development of of bacilli and the development of meningitis.meningitis.

The presence of bacilli in the subarachnoid space is The presence of bacilli in the subarachnoid space is followed byfollowed by an intense granulomatous inflamation ofan intense granulomatous inflamation offollowed by followed by an intense granulomatous inflamation of an intense granulomatous inflamation of the leptomeninges and subjacent cortex.the leptomeninges and subjacent cortex.

A thick, heavy fibrous and necrotic exudateA thick, heavy fibrous and necrotic exudate is is produced, which tends to collect at the produced, which tends to collect at the base of the base of the b ib ibrain.brain.

The arteries at the base of the brain are involved andThe arteries at the base of the brain are involved andThe arteries at the base of the brain are involved, and The arteries at the base of the brain are involved, and there is inflamation of the adventitia and media, with there is inflamation of the adventitia and media, with narrowing and thrombosis of the lumen.narrowing and thrombosis of the lumen.ggCN II and III, occasionally CN VII, VIII, are subject to CN II and III, occasionally CN VII, VIII, are subject to compression by the heavy exudate.compression by the heavy exudate.

Clinical features TBMClinical features TBMClinical features TBMClinical features TBM

The disease occurs in all ages, but the incidenceThe disease occurs in all ages, but the incidenceThe disease occurs in all ages, but the incidence The disease occurs in all ages, but the incidence is higher in infants, young children, and the is higher in infants, young children, and the aged. It is more common amomg the aged. It is more common amomg the undernourished and in those areas of the world undernourished and in those areas of the world characterized by characterized by poor hygiene and poor hygiene and

didiovercrowdingovercrowding..History of contact with an infected individual or a History of contact with an infected individual or a history previous active tuberculosis inhistory previous active tuberculosis in 30 to 5030 to 50history previous active tuberculosis in history previous active tuberculosis in 30 to 50 30 to 50 percent of patients.percent of patients.

Clinical staging of patients with Clinical staging of patients with TBMTBM

(terminus/ advance)

The course of the illness depends:The course of the illness depends:The course of the illness depends:The course of the illness depends:-- on the extend of meningeal involvement,on the extend of meningeal involvement,

th i f th h tth i f th h t-- the immune response of the host,the immune response of the host,-- the virulence of the organism,the virulence of the organism,-- and the stage at which treatment is and the stage at which treatment is administeredadministeredadministered.administered.

Kategori diagnosis OgawaKategori diagnosis OgawaDefiniteDefinite

-- bila kultur bila kultur positi-- otopsi positip, atau keduanyaotopsi positip, atau keduanyaP b blP b blProbable Probable

-- likuor pleiositosis (>5/mmlikuor pleiositosis (>5/mm33), kultur bak), kultur bak--teri dan jamur negatip + salah satu:teri dan jamur negatip + salah satu:teri dan jamur negatip salah satu:teri dan jamur negatip salah satu:1. test tuberkulin positip1. test tuberkulin positip2. TB diluar SSP atau TB aktip sebelumnya2. TB diluar SSP atau TB aktip sebelumnya3. glukosa likuor < 40 mg/dl3. glukosa likuor < 40 mg/dl4. protein likuor > 60 mg/dl4. protein likuor > 60 mg/dl

ComplicationComplicationComplicationComplication

ArteritisArteritis thrombosis of a major arterythrombosis of a major arteryArteritis Arteritis thrombosis of a major arterythrombosis of a major arterycerebral infarction.cerebral infarction.HydrocephalusHydrocephalusHydrocephalusHydrocephalusSeizuresSeizuresFocal motor deficits and impaired cognitiveFocal motor deficits and impaired cognitiveHypopituitarism in childhood.Hypopituitarism in childhood.yp pyp p

Differential DXDifferential DXDifferential DXDifferential DX

Viral encephalitisViral encephalitisViral encephalitisViral encephalitisPartially treated pyogenic meningitisPartially treated pyogenic meningitisF l i f tiF l i f tiFungal infectionFungal infectionOther inflammatory disordersOther inflammatory disordersThe presence of active TB elsewhere, and The presence of active TB elsewhere, and the results of CSF examination are usually the results of CSF examination are usually yysufficient to establish the dx.sufficient to establish the dx.

Diagnostic ProseduresDiagnostic ProseduresDiagnostic ProseduresDiagnostic Prosedures

1 Lumbal Puncture1 Lumbal Puncture1. Lumbal Puncture1. Lumbal PunctureCSF Parameter TB meningitisCSF Parameter TB meningitis

WBC C t 500/ l MNWBC C t 500/ l MN•• WBC Count < 500/ ul, MNWBC Count < 500/ ul, MN•• Gluco moderate or marked decreaseGluco moderate or marked decrease•• Protein marke increseProtein marke increse•• Gram stain + +Gram stain + + --Gram stain + +.Gram stain + +.•• CSF lactic acid > 35 mg/dl.CSF lactic acid > 35 mg/dl.

2. Laju endap Darah2. Laju endap Darahj pj p3. Radiologic3. Radiologic

3a. Chest x ray: detect pulmonary involvement3a. Chest x ray: detect pulmonary involvement3b CT 83b CT 8 h t f thh t f th3b. CT scan8 3b. CT scan8 enhancement of the enhancement of the

basal cistern.basal cistern.3b. MRI are more sensitive than CT3b. MRI are more sensitive than CT3b. MRI are more sensitive than CT 3b. MRI are more sensitive than CT

sans in detecting basal meningitis sans in detecting basal meningitis infarction owing to arteritis hydrocephalus infarction owing to arteritis hydrocephalus and parenchymal tuberculomas often in and parenchymal tuberculomas often in combination in AIDS patient.combination in AIDS patient.

4 Arteriografi4 Arteriografi4. Arteriografi4. Arteriografi

Images of CT ScansImages of CT ScansImages of CT ScansImages of CT Scans

file 1:file 1: ContrastContrast--file 1:file 1: ContrastContrastenhanced computed enhanced computed tomography (CT) scan in tomography (CT) scan in g p y ( )g p y ( )a patient with a patient with tuberculous meningitis tuberculous meningitis d t ti k dd t ti k ddemonstrating marked demonstrating marked enhancement in the enhancement in the basal cistern andbasal cistern andbasal cistern and basal cistern and meninges, with dilatation meninges, with dilatation of the ventriclesof the ventriclesof the ventricles.of the ventricles.

file 2:file 2: PetechialPetechialfile 2:file 2: Petechial Petechial hemorrhages in the hemorrhages in the subcortical white matter ofsubcortical white matter ofsubcortical white matter of subcortical white matter of the brain as a result of the brain as a result of tuberculous meningitistuberculous meningitis––tuberculous meningitistuberculous meningitisassociated vasculitis.associated vasculitis.

file 3:file 3: Extensive infarcts ofExtensive infarcts offile 3:file 3: Extensive infarcts of Extensive infarcts of the right basal ganglia and the right basal ganglia and internal capsule after the internal capsule after the appearance of vasculitis in appearance of vasculitis in the thalamoperforating the thalamoperforating

t i i hild t t d ft i i hild t t d farteries in a child treated for arteries in a child treated for tuberculous meningitis.tuberculous meningitis.

TreatmentTreatmentTreatmentTreatment1. Combination of antituberculous drug1. Combination of antituberculous drug

Therapy WHO GILROY ATSTherapy WHO GILROY ATS-- Initial Initial INH+R+PZA+E INH+R+PZA INH+R+PZA atau SINH+R+PZA+E INH+R+PZA INH+R+PZA atau S

atau R+ PZA+Satau R+ PZA+S

2MO2MO 2 MO2 MO 2 MO2 MO--2MO 2MO -- 2 MO 2 MO -- 2 MO2 MO-- Continued INH+R INH+R INH+RContinued INH+R INH+R INH+R

--7 MO 7 MO -- 9 MO 9 MO -- 9 MO9 MOPyridoxine 50 mg/ hrPyridoxine 50 mg/ hr

2. Spinal arachnoiditis and arteritis may show 2. Spinal arachnoiditis and arteritis may show improvement when terated with corticosteroid.improvement when terated with corticosteroid.pp3. Seizure 3. Seizure anticonvulsantanticonvulsant4. ventriculoperitoneal shunt.4. ventriculoperitoneal shunt.

PrognosisPrognosisPrognosisPrognosisMortality 10 & 20%Mortality 10 & 20%yyThe prognosis is poor in infants, the elderly, The prognosis is poor in infants, the elderly, when treatment is delayed, and in patients with when treatment is delayed, and in patients with poor nutrition or debilation from HIV infection orpoor nutrition or debilation from HIV infection orpoor nutrition or debilation from HIV infection or poor nutrition or debilation from HIV infection or other chronic disease.other chronic disease.The outcome is clearly associated with the stage The outcome is clearly associated with the stage

f th di t d d th i t d ti f lf th di t d d th i t d ti f lof the disease at dx and the introduction of early of the disease at dx and the introduction of early treatment. Those who are conscious and without treatment. Those who are conscious and without neurological deficits have a good prognosis; neurological deficits have a good prognosis; h i h b i i fh i h b i i fthose in coma at the beginning of treatment those in coma at the beginning of treatment

have 20% mortality and only 20 oercent make have 20% mortality and only 20 oercent make complete recovery.complete recovery.p yp y

Viral meningitisViral meningitisViral meningitisViral meningitis

Viral meningitis shares clinical features withViral meningitis shares clinical features withViral meningitis shares clinical features with Viral meningitis shares clinical features with bacterial meningitis, but patients appear less ill bacterial meningitis, but patients appear less ill and the disease follows a more benign course.and the disease follows a more benign course.Headache, often meningismus and photophobia, Headache, often meningismus and photophobia, is often the presenting symptoms.is often the presenting symptoms.The most pathogens include herpes simplexThe most pathogens include herpes simplex--1 1 (HSV1), mumps, enterovirus, herpes zoster, (HSV1), mumps, enterovirus, herpes zoster,

d i d E i b id i d E i b iadenoviruses and Epstein barr virus.adenoviruses and Epstein barr virus.

Dx procedure Viral meningitisDx procedure Viral meningitisDx procedure Viral meningitisDx procedure Viral meningitis

Lumbal PunctureLumbal PunctureLumbal PunctureLumbal PunctureCells Glucose Protein Smear CSF lactic Cells Glucose Protein Smear CSF lactic

500 N l Mild i N 35 /dl500 N l Mild i N 35 /dl< 500 Normal Mild incr No org < 35 mg/dl< 500 Normal Mild incr No org < 35 mg/dlMN /mm3MN /mm3PCRPCRMRIMRI predominant temporal lobe and insularpredominant temporal lobe and insularMRI MRI predominant temporal lobe and insular predominant temporal lobe and insular changes in HSEchanges in HSE--1 and basal ganglia lesion in 1 and basal ganglia lesion in japanese encephalitisjapanese encephalitisjapanese encephalitis.japanese encephalitis.

TreatmentTreatmentTreatmentTreatment

Aciclovir 10 mg/ kg iv every 8 hours for 10Aciclovir 10 mg/ kg iv every 8 hours for 10--Aciclovir 10 mg/ kg iv every 8 hours for 10Aciclovir 10 mg/ kg iv every 8 hours for 1014 days.14 days.

FUNGAL MENINGITISFUNGAL MENINGITISFUNGAL MENINGITISFUNGAL MENINGITISETIOLOGYETIOLOGYFungi invade of CNS producing meningitis in a small fraction of Fungi invade of CNS producing meningitis in a small fraction of patients with systemic fungal infection (mycoses)patients with systemic fungal infection (mycoses)

The most pathogens are The most pathogens are Cryptococcus neoformans, Cryptococcus neoformans, Coccidiodes immitis, Candida albicans, Aspergillus, H. Coccidiodes immitis, Candida albicans, Aspergillus, H. C l t Bl t d MC l t Bl t d MCapsulatum, Blastomyces, and MucorCapsulatum, Blastomyces, and Mucor

Mucormycosis and aspergillosisMucormycosis and aspergillosis usually spreads to the CNSusually spreads to the CNSMucormycosis and aspergillosis Mucormycosis and aspergillosis usually spreads to the CNS usually spreads to the CNS from infected sinuses and generally cause local inflamation and from infected sinuses and generally cause local inflamation and necrosis rather than a diffuse meningitisnecrosis rather than a diffuse meningitis

Fungi can cause infection in patients with:Fungi can cause infection in patients with:1. Cancer1. Cancer2. Receiving corticosteroids2. Receiving corticosteroids3. Other immunosuppressive drugs3. Other immunosuppressive drugs3. Other immunosuppressive drugs3. Other immunosuppressive drugs

(Diabetes, malignancy, immunosuppressive (Diabetes, malignancy, immunosuppressive th., or AIDS)th., or AIDS)

4 IV drug abuse4 IV drug abuse4. IV drug abuse.4. IV drug abuse.

Route of entryRoute of entryA. Haematogenous: from the heart, lung, GIT and skinA. Haematogenous: from the heart, lung, GIT and skinB. Direct: from the orbit and paranasal sinuses.B. Direct: from the orbit and paranasal sinuses.B. Direct: from the orbit and paranasal sinuses.B. Direct: from the orbit and paranasal sinuses.

Clinical PictureClinical PictureClinical PictureClinical Picture

Symptoms progress over days sometimesSymptoms progress over days sometimesSymptoms progress over days, sometimes Symptoms progress over days, sometimes weeks, with headache, nausea, vomiting and weeks, with headache, nausea, vomiting and mild encephalopathymild encephalopathymild encephalopathy.mild encephalopathy.Neurologic examination:Neurologic examination:1 i l i it ti ( ) 5 Vi l l1 i l i it ti ( ) 5 Vi l l1. meningeal irritation (+) 5, Visual loss1. meningeal irritation (+) 5, Visual loss2. papilledema 6. Confusional state 2. papilledema 6. Confusional state 3. Cranial nerve palsies 7. Focal paralysis3. Cranial nerve palsies 7. Focal paralysis4 Ptosis4 Ptosis4. Ptosis4. Ptosis

InvestigationsInvestigationsInvestigationsInvestigationsLab investigations:Lab investigations:gg1. Blood culture1. Blood culture2. Serum glucose 2. Serum glucose gg3.Arterial blood gases3.Arterial blood gases4. Electrolyte4. Electrolyte5. Liver function test5. Liver function test6. Urinalysis6. UrinalysisCSF Examinations:CSF Examinations:ImagingImaging

InvestInvestInvest…..Invest…..CSF Exam:CSF Exam:-- Pressure: IncreasedPressure: Increased-- Appearance: varies with organismAppearance: varies with organism

Whi Bl d ll 50Whi Bl d ll 50 10 000 ( i d10 000 ( i d-- White Blood cells: 50 White Blood cells: 50 –– 10.000 (mixed or 10.000 (mixed or lymphocytic).lymphocytic).Glucose :NormalGlucose :Normal-- Glucose :NormalGlucose :Normal

-- Protein: increasedProtein: increased-- Cryptoccal antigen is more sensitiveCryptoccal antigen is more sensitiveC yptocca a t ge s o e se s t eC yptocca a t ge s o e se s t e-- Fungal culture of CSF(+)Fungal culture of CSF(+)

InvestInvestInvest….Invest….

Chest XChest X--ray : Hilar lymphadenopathyray : Hilar lymphadenopathyChest XChest X ray : Hilar lymphadenopathy, ray : Hilar lymphadenopathy, cavitation, effusion.cavitation, effusion.CT or MRI: mass lesion (Cryptococcus)CT or MRI: mass lesion (Cryptococcus)CT or MRI: mass lesion (Cryptococcus)CT or MRI: mass lesion (Cryptococcus)

TreatmentTreatmentTreatmentTreatment

Amphotericin BAmphotericin BAmphotericin BAmphotericin B-- Protocol, starting with 1 mg/ dayProtocol, starting with 1 mg/ day

d bli th d d il til hi 16d bli th d d il til hi 16-- doubling the dose daily until reaching 16 doubling the dose daily until reaching 16 mg per day, than increasing at increments mg per day, than increasing at increments of 10 mg until reaching full therapeutic of 10 mg until reaching full therapeutic dose of 0 5 to 1 5 mg/ kg per day IVdose of 0 5 to 1 5 mg/ kg per day IVdose of 0,5 to 1,5 mg/ kg per day IV.dose of 0,5 to 1,5 mg/ kg per day IV.