INFECTIONS OF THE CENTRAL NERVOUS SYSTEM

Dr. Kiking Ritarwan, SpS(K), MKT Departement of Neurology Medical Faculty of University of Sumatera Utara

CNS INFECTION
MENINGITIS - Inflamation of the meningeal covering of Brain and spinal cord. - LEPTOMENINGITIS (arachnoid + pia) PACHYMENINGITIS (duramater) - TYPE OF MENINGITIS : Bacterial, TB, Viral, fungal. ENCEPHALITIS VIRAL MYELITIS ABSCESS CEREBRI CEREBRAL MALARIA NCC

ANATOMI MENINGS

Acute Pyogenic Meningitis = Bacterial meningitis

Is an inflamatory response to bacterial infections involving the pia and arachnoid membrane covering the brain and spinal cord. Many org. can produce pyogenic meningitis It can be categorised into: a. Spontaneous community acquired meningitis b. Post traumatic meningitis following neurosurgery or fx of the skull. c. Device associated meningitis particularly in assoc. With CSF Shunts and drain.

The causative org. of meningitis can be predicted based on the patients age, exposure to an epidemic, vacc. Against common agents (eg. H. Influenza, Streptococcus pneumonie, N. meningitidis) and Immune state. Pathology is characterized by inflammation of the meninges and cortical blood vessels.

Etiology of Bacterial meningitis

Age - Neonate ( 0-2 bln) Microorg. Streptococ group B, E coli, list. Stap. Aureus, Enterobacter, Pseudomonas, Haemofilus S. pneumonie, N. meningitidis, H. influenzae. N. meningitidis, S. pneumonie,H. infl. S. pneu, N. meningi, Streptococ,Staph.

- Child - Youth ( 6-20th) - Adult ( > 20 thn)

Clinical Picture
The conditions occurs equally in both sexes Children aged 6 month to 1 year are at the greatest risk and children under 15 years of age comprise 75% of all cases. Patients aged 60 and older may be atypical. Symptoms and signs I. early infection: fever, headache, malaise,vomite II. Higher ICP: vomite, headache, seizure, alteration of consciousness, papiledema III. Meningeal irritation: nuchal rigidity, Kernig and Brudzinski + IV. CSF:neutrophilic pleocytosis, low glucose level, elevated protein concentration

CSF Findings
CSF Parameter WBC Count Glucose Protein Gram stain + Culture + Bacterial meningitis > 2000/ ul, >60% PMN < 40 mg/ dl > 200 mg/ dl 80% > 90%

Diagnostic Prosedure
Lumbal Puncture Blood should be drawn for blood culture before administration of antibiotic. Bacterial antigen Chest, skull mastoid and paranasal sinus x rays MRI or CT Neuroimaging shoul be performed before LP in the following settings:60 yo or older, Depressed LOC, Focal neurologic signs, papilledema, Patients is immunocompromised.

Treatment
1.Antibiotic therapy should be administrated. A minimum of 2 weeks of therapy is recommended. Age Antibiotic 0 4 mgg Cefotaxim + Ampi 4-12 mgg Gen III. Cephalos+ Ampi 3 bln- 18 thn Gen III. Ceph + Ampi atau Ampi + chloramph. 18 thn 50 thn Gen III. Ceph + Ampi 50 thn Gen III. Ceph + ampi. 2. When possible etiologies for meningitis include H. Influenza or S Pneumoniae in child, or S Pneumoniae in adults, give dexamethasone 0,15 mg/kg (IV) every 6 hours for 2-4 days in child and 10 mg IV every 6 hours for 4 days in adults.

Complication Bacterial meningitis

Cerebral abscess Empyema subdural Convulsie Shock septic Cerebral edema Infarck serebral Herniation

Sequele bacterial meningitis

Mental retardation Hydrocephalus Convulsie, psikose Parese, deafness, blind.

Tuberculous meningitis
The first clinical description of tuberculous meningitis in the late 18th Century is credited to the Scottish physiologist Sir 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 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 hematogenous spread infection to the brain parenchyma or meninges.

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

+ 1,7 milyar people ( 1/3 worldwide people) Mycobacterium tuberculosa infected. Reported CDC 2002 was 5,36 cases per 100.000 people, but worldwide the infection rate is much higher. TB in Indonesian occupy 3rd rank from 22 high burden countries.

Indonesia
22 High Burden Countries
1. 2. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. India China Bangladesh Nigeria Pakistan South Africa Philippines Russia Ethiopia Kenya DR Congo Viet Nam UR Tanzania Brazil Thailand Zimbabwe Cambodia Myanmar Uganda Afghanistan Mozambique

3. Indonesia

Indonesia 10%
Bangladesh 4% Pakistan 4% Philippines 3% Nigeria 3% South Africa 2% Russia 1%

China 15%

India 30%

Other 28%

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

Tuberculosis

Diarrheal disease
Perinatal causes 3% Chronic obstructive pulmonary disease HIV/AIDS Respiratory tract infection 5% 7% Injury 9% 4% 3% 2%

Malaria

5%
Other 27%

Stroke 10%

Coronary heart disease 13% Cancer 12%

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.

Etiologi
Mycobacterium tuberculosis gol ordo Actinomycetales, famili Mycobacteriaceae, genus Mycobacterium Sifat : aerob, spora (-), motil (-), berkembang biak lambat Mati dgn pemanasan & sinar UV Bakteri batang tahan asam dgn pewarnaan ZiehlNeelsen /Auramin leading to nickname red snapper.

Size :0,3-,0,6 to 1-4 um Shape: Rods, straight or slightly curved, occurring singly or in occasional threads Temperature: 33-39o C pH 6,6-6,8

PATHOLOGY

Aerosol transmission of Tuberculosis

Tuberculosis is spread by droplet nuclei which are expelled when a person with infectious TB coughs, sneezes, speaks, or sings

Pathology
TBM is always secondary to TB elsewhere in the body. The primary focus of infection is usually in the lungs but may be in the lymph glands, bones, nasal sinuses, GIT, or any organ in the body. The bacilli usually enter the body by inhalation. Transmission through the skin or by ingestion are rare cause of infection. The organisms undergo multiflication and hematogenous dissemination and it is during this stage that the meninges are most likely to become involved.

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

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

A thick, heavy fibrous and necrotic exudate is produced, which tends to collect at the base of the brain.
The arteries at the base of the brain are involved, and there is inflamation of the adventitia and media, with narrowing and thrombosis of the lumen. CN II and III, occasionally CN VII, VIII, are subject to compression by the heavy exudate.

Clinical features TBM

The disease occurs in all ages, but the incidence is higher in infants, young children, and the aged. It is more common amomg the undernourished and in those areas of the world characterized by poor hygiene and overcrowding. History of contact with an infected individual or a history previous active tuberculosis in 30 to 50 percent of patients.

Clinical staging of patients with TBM

(terminus/ advance)

The course of the illness depends: - on the extend of meningeal involvement, - the immune response of the host, - the virulence of the organism, - and the stage at which treatment is administered.

Kategori diagnosis Ogawa

Definite - bila kultur positi - otopsi positip, atau keduanya Probable - likuor pleiositosis (>5/mm3), kultur bakteri dan jamur negatip + salah satu: 1. test tuberkulin positip 2. TB diluar SSP atau TB aktip sebelumnya 3. glukosa likuor < 40 mg/dl 4. protein likuor > 60 mg/dl

Complication
Arteritis thrombosis of a major artery cerebral infarction. Hydrocephalus Seizures Focal motor deficits and impaired cognitive Hypopituitarism in childhood.

Differential DX
Viral encephalitis Partially treated pyogenic meningitis Fungal infection Other inflammatory disorders The presence of active TB elsewhere, and the results of CSF examination are usually sufficient to establish the dx.

Diagnostic Prosedures
1. Lumbal Puncture CSF Parameter TB meningitis WBC Count < 500/ ul, MN Gluco moderate or marked decrease Protein marke increse Gram stain + +.CSF lactic acid > 35 mg/dl.

2. Laju endap Darah 3. Radiologic 3a. Chest x ray: detect pulmonary involvement 3b. CT scan8 enhancement of the basal cistern. 3b. MRI are more sensitive than CT sans in detecting basal meningitis infarction owing to arteritis hydrocephalus and parenchymal tuberculomas often in combination in AIDS patient. 4. Arteriografi

Images of CT Scans
file 1: Contrastenhanced computed tomography (CT) scan in a patient with tuberculous meningitis demonstrating marked enhancement in the basal cistern and meninges, with dilatation of the ventricles.

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

file 3: Extensive infarcts of the right basal ganglia and internal capsule after the appearance of vasculitis in the thalamoperforating arteries in a child treated for tuberculous meningitis.

Treatment
1. Combination of antituberculous drug Therapy WHO GILROY ATS - Initial
INH+R+PZA+E INH+R+PZA atau R+ PZA+S INH+R+PZA atau S

-2MO - 2 MO - 2 MO - Continued INH+R INH+R INH+R -7 MO - 9 MO - 9 MO Pyridoxine 50 mg/ hr 2. Spinal arachnoiditis and arteritis may show improvement when terated with corticosteroid. 3. Seizure anticonvulsant 4. ventriculoperitoneal shunt.

Prognosis
Mortality 10 & 20% The prognosis is poor in infants, the elderly, when treatment is delayed, and in patients with poor nutrition or debilation from HIV infection or other chronic disease. The outcome is clearly associated with the stage of the disease at dx and the introduction of early treatment. Those who are conscious and without neurological deficits have a good prognosis; those in coma at the beginning of treatment have 20% mortality and only 20 oercent make complete recovery.

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

Dx procedure Viral meningitis

Lumbal Puncture Cells Glucose Protein Smear CSF lactic < 500 Normal Mild incr No org < 35 mg/dl MN /mm3 PCR MRI predominant temporal lobe and insular changes in HSE-1 and basal ganglia lesion in japanese encephalitis.

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

FUNGAL MENINGITIS
ETIOLOGY Fungi invade of CNS producing meningitis in a small fraction of patients with systemic fungal infection (mycoses)
The most pathogens are Cryptococcus neoformans,

Coccidiodes immitis, Candida albicans, Aspergillus, H. Capsulatum, Blastomyces, and Mucor

Mucormycosis and aspergillosis usually spreads to the CNS

from infected sinuses and generally cause local inflamation and necrosis rather than a diffuse meningitis

Fungi can cause infection in patients with: 1. Cancer 2. Receiving corticosteroids 3. Other immunosuppressive drugs (Diabetes, malignancy, immunosuppressive th., or AIDS) 4. IV drug abuse.

Route of entry A. Haematogenous: from the heart, lung, GIT and skin B. Direct: from the orbit and paranasal sinuses.

Clinical Picture
Symptoms progress over days, sometimes weeks, with headache, nausea, vomiting and mild encephalopathy. Neurologic examination: 1. meningeal irritation (+) 5, Visual loss 2. papilledema 6. Confusional state 3. Cranial nerve palsies 7. Focal paralysis 4. Ptosis

Investigations
Lab investigations: 1. Blood culture 2. Serum glucose 3.Arterial blood gases 4. Electrolyte 5. Liver function test 6. Urinalysis CSF Examinations: Imaging

Invest..
CSF Exam: - Pressure: Increased - Appearance: varies with organism - White Blood cells: 50 10.000 (mixed or lymphocytic). - Glucose :Normal - Protein: increased - Cryptoccal antigen is more sensitive - Fungal culture of CSF(+)

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

Treatment
Amphotericin B - Protocol, starting with 1 mg/ day - doubling the dose daily until reaching 16 mg per day, than increasing at increments of 10 mg until reaching full therapeutic dose of 0,5 to 1,5 mg/ kg per day IV.

Myelitis
Inflamation of the spinal cord I. Transverse Myelitis, II. Disseminata, III. Difussa Transverse myelitis (MYELOPATHY) is a syndrome characterized by acute spinal cord dysfunction both halves the cord in transverse section.

Myelitis transversalis
inflamasi akut atau sub akut mengenai suatu area fokal di medula spinalis karakteristik klinis disfungsi neurologis pada saraf motorik, sensorik dan otonom dan traktus saraf di medula spinalis

MYELITIS
Gray matter Poliomyelitis. White matter . Leukomyelitis. The whole crossectional areTranversemyelitis. Lesions are multiple and wide spreadOver a long vertical extent.. DiffuseOr Disseminated. Combined meninges and spinal cordMeningomyelitis. Combined meninges and root--- meningpradiculitis. Inflammatory disease limited to the spinal dura. Pachymeningitis. Infected material collects in the epidural or subdural space Epidural spinal Or subdural spinal abcess or Granulomatous.

CLASSIFICATION OF INFLAMMATORY DISEASE OF THE SPINAL CORD SEE TRANSPARANTS

ACUTE TRANSVERSE MYELITIS

IS USUALLY BILATERAL AND TENDS TO CAUSE MORE SEVERE WEAKNESS THAN THE TYPICAL ATTACKS OF PARTIAL MYELITIS. The condition may be peri infectious or postinfectious process and has been associated with many viral infection, including poliovirus, echovirus and coxsackieviruses.

Etiologie Transverse myelitis

1. Congenital vascular malformation 2. Infectious viral infection 3. Autoimune- peri or post infection or vaccinial myelitis. 4. Multiple sclerosis 5. Neoplastic 6. Toxic- secondary to heroin injection 7. Vascular 8. Degenerative- irradiation 9. Idiopathic.

PATOLOGI
JHTMC (John Hopkins Transverse Myelitis Center) kondisi inflamasi yang berhubungan dengan mekanisme immune-mediated Pasien myelitis transversalis perubahan inflamasi pada medula spinalisnya Abnormalitas patologi ( bervariasi )
infiltrasi lokal oleh limfosit dan monosit dalam segmen medula spinalis dan daerah perivaskuler adanya aktifitas yang bervariasi dari mikroglia dan astroglia

Besar dan luasnya gambaran inflamasi faktor etiologi dan profile perubahan myelopati :
Myelitis post infeksius perubahan white matter, demielinasi, gangguan aksonal myelitis transversalis gambaran yang melibatkan keduanya secara bersamaan baik white maupun grey matter

Viral causes of acute myelitis

Herpesvirus: HSV2, Varicella Zoster, HSV1, Epstein barr, Cytomegalo, human herpes6. Enterovirus: Poliovirus, Enterovirus 70, Echovirus, Coxsackievirus. Arbovirus: west nile virus Other: Mumps, HIV, Dengue.

Affinities virus in myelitis

Enterovirus anterior horn or nuclei of the brain stem Herpes zoster dorsal root ganglion

Clinical manifestation
Acute paraplegic or Quadriplegic. Urinary retention. Sensory disturbances

Diagnostic prosedure
CSF examination: - mild to moderate lymphocytic pleocytosis (10-1000 cell/mm3), elevated protein (100-500 mg/dl), and normal or mildly depressed glucose level. PCR- virus spesific PCR and antibody titer should be performed. MRI-T2 weighted shows increased signal intensity involving gray matter and surronding white matter.

DIAGNOSIS BANDING : Multiple sclerosis Penyakit sistemik (SLE, Sjorgen disease) Venous infarct Malformasi vaskuler (fistula AV, AVM, angioma kavernosa) Fibrocartilagenous embolism Myelopati radiasi

Treatment Viral myelitis

Antiviral treatment: Glucocorticoid Spasticity: baclofen (lioresal) 10 mg q6h, benzodiazepin and tizanidine.

BRAIN ABSCESS Definition

Brain abscess is a focal intracerebral infection that begin as a localized area of cerebritis and develops into a collection of pus surrounded by a weil-vascularized capsule. Abscess of the brain has been known for over 200 years, and surgical treatment started with MacEwen in 1893 [published: pyogenic infective disease of the Brain].

Parenchymal brain infection can arise from hematogenous delivery of infected material, which often results in multiple abscess. Especially at risk are patients with congenital heart disease or valve infection. Pathogenesis: abscess begin with local cerebritis, causing necrosis and surronding edema. Epidemiology: 0,3 1,3 per 100.000 / tahun Male to female ratio of 2:1 to 3:1

Common etiologic factors

Common etiologic factors
Distingushing characteristics
Ear inf: temporal lobe abscess, sinus inf: frontal lobe abscess, mastoid inf: cerebellar abscess

Middle ear,paranasal sinus, or mastoid infection

Metastatic embolic from lung, pulmonary abscess, bronchietasis, or chronic empyema

Multiple abscess
Gunshot wounds are the most common head trauma assc. With abscess

Head trauma or Neurosurg.

Endocarditis
Rare cause: dental procedures, Metastatic emboli from abdominal inf. Or PID, osteomyelitis of skull

Drug abuser -

Common etiologic factors Microorgnism involved Aerobes Anaerob Streptococci, Streptococci Middle ear,paranasal Staph aureus Bacteriodes sinus, or mastoid infection
Metastatic embolic from lung, pulmonary abscess, bronchietasis, or chronic empyema
Staph aureus, Klebsiela S.Pneumoniae Streptococci, Fusobacteria

Head trauma or Neurosurg. Endocarditis

Rare cause: dental procedures, Metastatic emboli from abdominal inf. Or PID, osteomyelitis of skull

Staph aureus, Pseudomonas

streptococci

Staph aureus

RISK FACTORS AND PATHOGENESIS CEREBRAL ABSCESS Directly from the paranasal sinuses, mastoid, middle ear or via hematogenous spread e.g. colonic diverticulae,
pulmonary infection, periodontal infection, bacterial endocarditis, except rabies (infiltration along peripheral nerve), Naegleria and herpes via the olfactory bulbs

Bacterial caused by aerobic and anaerobic gram negative/positive The source of inoculation of CNS remain unknown in up to one-third Head trauma : CSF leak, reoperation, delay in care or basilar skull fracture Implantation of a foreign body : shunt, high-grade glioma, irradiation Immunocompromised : transplant, cancer, chemotherapy,
retroviral infection

Neuropatologi (4 stages)
Early cerebritis ( days 1-3) infection of the brain with surronding white matter edema. 2. Late cerebritis ( days 4-9) The core of the cerebritis becomes necrotic and enlarges and capsular fibroblasts begin to form. 3. Early capsule formation ( days10-13) The capsule is well developed, with proliferation of fibroblasts, a surronding astrocytic proliferation, and edema 4. Late capsule formation (days 14 or more). A mature, thick capsule surronds the central cavity containing debris and PMN cells. There is usually marked cerebral edema in the surronding brain tissue in the presence of a mature abscess.
1.

Gejala dan tanda klinis:

Sakit kepala (70-90%) Muntah (25-50%) Kejang(30-50%) Gejala pusing, vertigo, ataksia ( pd abses cerebelli) Ggn bicara (19,6%), hemianopsia (31%), unilateral midriasis (20,5%) Gejala fokal (61%) pd penderita abses supratentorial.

Pemeriksaan utk Diagnosa:

Glasgow coma scale : utk kesadaran penderita Rontgen foto kepala, sinus, mastoid, thoraks. EEG CT Scan/ MRI Cerebritis results in a non homogeneous mass with irregular margins and diffuse enhancement Angiografi : utk menentulan lokasi abses (24%). Lab: jlh leukosit 10.000-20.000/ cm3 (60-70%) LED meningkat 45 mm/jam (75-90%).

Head Ct San

A. Multiple brain abscesses associated with bacterial endocarditis (Staphylococcus aureus) in a 55-year-old man. The large abscess in the left hemisphere shows a characteristic ring enhancement. B. Contrastenhanced CT scan 4 months after institution of antibiotic treatment. The abscesses have resolved.

TEMPORAL LOBE ABSCESS

CT scan showing ring enhancement in temporal sinistra (hyperdense capsule differentiated from central low density (pus) and marked surronding edema)

Komplikasi Abses Otak

Robeknya kapsul abses kedalam ventrikel atau keruangan subarakhnoid. Penyumbatan cairan serebrospinal hidrosefalus Edema otak Herniasi tentorial oleh massa abses otak.

Pengobatan abses otak

Konservatif:
mengecilkan abses. - Prinsip pemberian AB: bakterisid thdp organisme hasil kultur, dapat melewati BBB. - Pemberian kortikosteroid: dewasa : loading dose 10-12 mg secara IV maintenance dose 4 mg secara IV setiap 6 jam anak : loading dose 10-12 mg/kg diberikan satu kali IV maintenance dose 1-1,5 mg/kg/hari IV - Pemberian antikonvulsan Operatif: Aspirasi dan eksisi. konsul Bedah Saraf , jika terapi konservatif gagal.
72

- Pemberian AB yg tepat : 6-8 mgg

SURGICAL MANAGEMENT CEREBRAL ABSCESS

Stereotactic aspiration Advantages : Avoidance of general anesthesia Access to multiple lesions without an increase in surgical complexity Ability to decompress lesions in eloquent areas such as the thalamus and basal ganglia Simple cystic structure ; size <1.5 cm ; deep gray matter ; no air/fluid level ; no fistula Complication : intracerebral hematoma 0.4% to 1.6% Mortality less than 0.2% ; morbidity 1-4%
Open craniotomy with or without excision of the capsule Posterior fossa masses indicate for open craniectomy ; encapsulated ; silent cortex or white matter

Multiloculated abscesses, which are difficult to fully decompress stereotactically, should open ; size >2.5 cm ; air/fluid level in abscess ; fistula
Mortality 1% to 11% ; morbidity 4% to 30%

The goal treatment in brain abscesses :

Reduce mass effect Decrease intracranial pressure Prevent herniation or intraventricular rupture and ventriculitis Identify the causative microorganism Establish antibiotic sensitivities

Antibiotic treatment for brain abscess

Rational Administration

:Timing of initial therapy, Choice of agents,

Metronidazole 7.5 mg IV every 6 h + Cefepime 2 gr IV every 6 h or meropenem 2gr IV every 8 h

Penetration of various agents into the brain, Duration of therapy

Ear, mastoid, sinus

Streptococcal species, Ps anaerobes,

Enterobaceteriacea

Lung

S. pneumoniae

Same as above

AB treatment
Teeth, mouth Anaerobic streptococci, Eikenella, Prevotella, Actinomyces Staphiloc
Metro 7,5 mg/kg IV every 12 h + PNC G 4million units IV every 4 h or ceftizoxime 3 gr IV every 6 h Cefepime 2 gr IV every 8 h, or Nafcillin or oxacillin 2 g IV every 4 h

Post operative infection, furuncles or decubiti

NEUROLOGICAL SEQUELAE
Most likely due to :
Delayed diagnosis Poor initial neurological conditions Larger size

Common neurological sequelae are cognitive defisits, hemiparesis, and seizures Infants and children have a worse outcome than adults ,IQ lower than 80, 70% children had difficulties with school performance, 38% had severe hemiparesis Adult : 87% were able to continue their normal work and none had severe hemiparesis

Seizure disorders
3 to 4 years after treatment (15% to 92%) Children are more likely than adults Most common lesion at frontal and temporal lobes ; occipital lobe are unusual ; cerebellar do not predispose to seizures

Anticonvulsant for at least 6 months Rates of recurrence 10% to 50%

PROGNOSIS Cerebral Abscess

Mortality > 60% if sign of brain herniation are present Mortality rate <29% among alert patients 90% among comatose patients Mortality rate 12.5% in posttrauma without signs of herniation Mortality rate 4.3% since CT became a routine diagnotic test Sex and ethnic origin is no evidence for mortality High mortality rate in :
Patients related to immaturity Virulence of the gram-negative organisms Coexistent systemic disease

Defenition Viral encephalitis

Is an acute febrile illness with evidence of damage to the parenchymal tissue of the CNS, producing alteration of consciousness, focal neurological signs and seizures. Etiology:viral infection of the nervous system, Herpes simpleks Eastern equine Venezuela St Louis Japanese B Russian tick-borne Rabies

Etiology viral encephalitis

Viral is the most common cause The commonest is HSV type I in adults

and type 2 in neonates. It may occur sporadically or in epidemics 50-70% mortality if untreated So establishment of on early specific diagnosis and early initiation of antiviral chemotherapy is of great importance 2/3 of cases involve patients over 40 yo.

Patogenesis.
Bila virus patogen masuk kedalam tubuh pada SSP dapat terjadi: Radang akut Radang kronis Neoplasma Virus hidup dalam keadaan laten

Cara penyebaran ke SSP: Cara penyebaran Contoh virus

Hematogen herpes simplex sitomegalovirus Epstein-Barr Coxsackie HIV Morbilli Echovirus khoriomeningitis limfositik paravirus

Neurogen

Herpes simpleks B-virus Varisela-Zoster Rabies

Gambaran klinik:
Tanda dan gejala bervariasi tergantung virus penyebab. Umumnya: demam akut disertai tanda rangsang meningeal, sakit kepala, mual, fotofobi, muntah, ggn kesadaran, defisit neurologik fokal dan kejang2. Mortalitas bervariasi dari tinggi (eastern equine encephalitis) sampai rendah (Venezuelan equine encephalitis).

Gejala sisa termasuk kejang2 Komplikasi : - perubahan kepribadian - ggn ekstrapiramidal - demensia - ggn motorik - sensorik

Kriteria diagnosis ensefalitis viral

Bentuk asimptomatik analisis LP Bentuk abortif : Nyeri kepala, demam yg tdk tinggi, kaku kuduk. ISPA/ Infeksi GIT 3. Bentuk fulminan: Berlangsung bbrp jam sampai dengan beberapa hari yg berakhir dengan kematian. 4. Bentuk khas ensefalitis: NK, demam, keasadaran menurun, kejang fokal atau umum, hemiparesis, ggn koordinasi, disorientasi, ggn bicara, ggn mental
1. 2.

Prosedur diagnostik.
LP : CSF jernih, tekanan normal atau meningkat, Pleositosis limfositik < 1000/ul, glukosa dan klorida nornal, protein normal atau sedikit meninggi ( 80-200 mg/dl MRI atau CT scan SOL (?) EEG Liquor virus DNA dg polymerase chain reaction (prosedur cepat, sensitif, akurat) Virus kadang2 dikultur dari liquor,feces,urine nasofaring atau darah. Titer antibodi thd virus tertentu.

Pengobatan.
Tidak bisa diidentifikasi dianggap sebagai ensefalitis herpes simpleks dan terapi dgn. Acyclovir atau ganciclovir Jalan nafas diawasi Keseimbangan cairan dan elektrolit dijaga Atasi kejang Atasi peninggian ICP

Spektrum NeuroAIDS
Primary complication (nonopportunistic disease) HIV-Dementia HIV-Sensory neuropathy Secondary complication (opportunistic disease) Cerebral Toxoplasmosis TB Meningitis / tuberculoma Cryptococcal meningitis Other opportunistic diseases....

Komplikasi neurologi HIV

Brain Predominantly nonfocal AIDS dementia complex Acute HIV-related encephalitis Cytomegalovirus encephalitis Varicella-zoster virus encephalitis Herpes simplex virus encephalitis Metabolic encephalopathies

Predominantly focal Cerebral toxoplasmosis Primary CNS lymphoma Progressive multifocal leukoencephalopathy Cryptococcoma Brain abcess / tuberculoma Neurosyphilis (meningovascular) Vascular disorders

Spinal cord Vacuolar myelopathy Herpes simplex or zoster myelitis Meninges Aseptic meningitis (HIV) Cryptococcal meningitis Tuberculous meningitis Syphilitic meningitis Metastatic lymphomatous meningitis

Peripheral nerve and root and root infectious herpes zoster cytomegalovirus lumbar polyradiculopathy Virus or immune-related acute and chronic inflammatory HIV polyneuritis mononeuritis multiplex sensorimotor demyelinating polyneuropathy distal painful sensory polyneuritis Muscle polymyositis and other myopathies

Perjalanan penyakit infeksi HIV

Infeksi virus (2-3 minggu) sindroma retro- viral akut (2-3 minggu) gejala menghilang + serokonversi infeksi kronis HIV asimpto matik (rata2 8 thn) infeksi HIV / AIDS simptomatik (rata2 1,3 thn) kematian. Window period masa dimana pemeriksa- an test serologis utk antibodi HIV masih negatif, tapi virus sdh ada dlm darah (sudah mampu menularkan kpd orang lain)

HIV dementia (AIDS Dementia Complex)

This progressive dementia occurs in AIDS, owing to a direct primary HIV infection of neurons or an indirect neurotoxicity induced by presence of the virus in the brain Pathology: the virus may be transported into the brain by infected peripheral monocytes (Trojan horse theory).

Manifestasi klinis demensia HIV: Cognititive disorders Gangguan kognitif, kesulitan konsentrasi, forgetfullness, cognitive slowing. Kadang2 agitasi, mania. Pd std awal sulit membedakan dgn keluhan psikiatri. Motor abnormalities: ataksia, hiperreflels. Babinski refleks srg muncul. Pada std lanjut : paraparese dgn inkontinansia urin et alvii Behavioural dysfunction : Apathy, altered personality, disorientasi. Std akhir Mutism

CEREBRAL TOXOPLASMOSIS
Reactivation of latent infection Toxo seroprevalence 12-46% (SA) IgG indicates past infection (FN <3-6%)

CD4 > 200 virtually excludes Toxo Over 80% have CD4 < 100
Typically multiple ring enhancing lesions on CT/MRI 27-43% have single lesions Up to 10% may have diffuse encephalitis without any visible focal lesions

The course of HIV/AIDS

Notes:

Skema-1. Algoritme Penatalaksanaan Keluhan Intraserebral bagi Penderita HIV-AIDS

Keluhan intrakranial

MRI

CT Scan

normal

Atrofi

Meningeal enhancement

hidrosefalus

SOL

Evaluasi LCS

Shunt (kalau perlu)

Positif

Negatif Lesi massa(-) Lesi massa (+)

Terapi sesuai

Observasi Skema 2

etiologi

Skema-2. Algoritme Penatalaksanaan Lesi massa Intrakranial pada penderita HIV-AIDS

Lesi massa intrakranial

Alert-lethargic stabil

Steroid ?

Stupor-koma Perburukan cepat, massa besar Dengan resiko herniasi

Lesi multipel

Lesi tunggal

Serologi toksoplasma Positif Negatif

Obat antitoksoplasmosis Perbaikan

Ancaman herniasi

Ya

Tidak

Biopsi stereotaktik

Terapi toksoplasmosis Seumur hidup

Terapi sesuai etiologi

Dekompresi dan biopsi terbuka

Toxoplasmosis Clinical Features

Usually subacute over weeks Headache Fever Behaviour changes Confusion Focal signs Seizures 50% 45% 40% 15-52% 24-29%

TREATMENT
Acute treatment : 3-6 weeks.
Induction : pyrimethamine 200 mg First line :
Pyrimethamin 75-100 mg/day + sulfadiazine + folinic acid or Pyrimethamin + clindamycin + folinic acid.

Second line :
Azithromycin, clarithromycin, or atovaquone can substitute for sulfadiazine.

Glucocorticoid life threatening condition.

TREATMENT
Maintenance :
Until the immune system has sufficiently reconstituted. Pyrimethamine and sulfadiazine or Pyrimethamine and clindamycin.

Stop :
Asymptomatik. CD4+ > 200/cmm until 6 months.

Fase akut (3-6 minggu)

Pilihan pertama Pyrimethamine oral 200 mg hari pertama, selanjutnya 50-75 mg/hr + leucovorin oral 10-20 mg/hr + sulfadiazine oral 1000-1500 mg/hr Pyrimethamine + leucovorin (dosis di atas) + clindamycin oral atau IV 4 x 600 mg

Pemeliharaan/rum atan
Pyrimethamine oral 25-50 mg/hr + leucovorin oral 10-20 mg/hr + sulfadiazine oral 500-1000 mg/hr.

Pilihan kedua Pyrimethamine + leucovorin (dosis di atas) + clindamycin oral 4 x 300 mg 450 mg Pyrimethamine + leucovorin (dosis di atas) + salah satu antibiotika tersebut dosis sama.

Pilihan ketiga

Pyrimethamine + leucovorin (dosis di atas) + salah satu : Atovaquone oral 2 x 1500 mg Azithromycin oral 1 x 900 1200 mg Clarithromycin oral 2 x 500 mg Dapson oral 1 x 100 mg Minocyclin oral 2 x 150-200 mg

107

CT - Multiple ring enhancing lesions

Toxo more likely Tuberculomas still possible

Differential Diagnosis
Toxoplasmosis
Location Number of lesion Enhancement pattern Edema T2-weighted image (lesion relative to white matter) Diffusion-weighted image Basal ganglia. Gray-white junction Multiple Ring Moderate to marked Hyperintense

P CNS L
Periventricular Solitary>multiple Heterogeneous or homogeneous. Variable Isointense to hyperintense. Often hyperintense (positive)

Usually hypointense

Differential Diagnosis
Toxoplasmosis
MR perfusion MR spectroscopy SPECT thallium (lesion relative to white matter) Decreased Markedly elevated lactate. Cold-no thallium uptake

P CNS L
Increased Markedly elevated choline Hot-increased thallium uptake.

Other

Toxoplasma IgG Ab EBV DNA amplified (+) (90% of patients) by PCR in CSF (most patients)

Malaria Serebral (MS)

MS adalah malaria dengan penurunan kesadaran ( dewasa GCS < 9 dan anak Blantyre coma score < 3) atau koma lebih dari 30 menit setelah serangan kejang yg tidak disebabkan oleh penyakit lain. MS komplikasi dari malaria falcifarum berat, dijumpai st ensefalopati difus dengan penurunan kesadaran dan berhubungan dengan sequestrasi mikrovaskuler serebral.

Blantyre coma scale(0-7)

Oculer response - Follow mothers facial reaction 1 - non reaction 0 Verbal response - Normal crying 2 - Whimpering 1 - no sound .. 0 Motoric response - Localize pain 2 - rettraction of limb ..1 - non reaction 0

Plasmodium falcifarum morphology in stained preparation

Ring form: vary in shape; double chromatin, double infection, accole Trophozoit: rare in peripheral blood after half grown

Plasmodium falciparum
Morphology of all stadiums

Patogenese
Ada 3 teori: 1. Teori mekanis : tjdnya penyumbatan pemb drh otak akibat tjdnya sitoadherens, sekuester, rosetting dan faktor rheologi. 2. Teori Toksik menghasilkan TNF 3. Teori Permeabilitas: tjdnya adhesi parasit pd endothel, vasculer serta banyak faktor toksik yg lepas serta radikal bebas terutama Nitric oxide (NO).

Diagnosa Malaria Serebral

Gjl Klinik : Trias malaria ( demam, menggigil, dan berkeringat), Sakit kepala, ggn mental, nyeri tengkuk, kaku otot dan kejang umum Sering dijumpai splenomegali dan hepatomegali Ggn kesadaran atau koma ( biasanya 24-72 jam) Pemr darah (thin/thick smear) dijumpai bentuk aseksual P. Falcifarum Tidak ditemukan infeksi lain Lain-lain:hipoglicaemia, hiponatremia, hipofosfatemia, pleocytosis sampai 80 cel/ micron kubik, limfosit sampai 15 cel/ mikron kubik CT/ MRI: edema serebri.

Laboratorium
Pemeriksaan dengan mikroskop - sediaan darah tebal dan tipis Test diagnostik lain - Metode immunokromatografi - Analisa cairan Serebrospinal pd Malaria serebral didapti peningkatan limfosit > 15/ul. - CT dan MRI: edema serebral

Comparison of diagnosis method

Clinical diagnosis Sensitivity 60-75% Microscopic 60-95% RDTs 44-100% 95% (only for Pf or Pv or Pan)

Specificity

30-40%

75-95%

Infrastructure needed Skill needed Cost

Minimal

High

Moderate

Minimal Cheap

High Moderate

Moderate Expensive

Pengobatan Malaria Tanpa Komplikasi

Malaria Falsiparum Lini pertama = Artesunat + Amodiakuin + Primakuin

Lini kedua = Kina + Doksisiklin atau Tetrasiklin + Primakuin

Pengobatan lini kedua diberikan jika pengobatan lini pertama tidak efektif, dimana 28 hari setelah pemberian obat : Gejala klinis memburuk dan parasit aseksual positif, atau
Gejala klinis tidak memburuk tetapi parasit aseksual tidak berkurang (persisten) atau timbul kembali (rekurensi)

Neurocisticercosis (NCC)
Def: cysticercosis cellulosa is the larval stage of development of the cestode Taenia solium (pork tapeworm). More than 60 million people are infected with T. saginata world wide and about 4 million are infected with T. solium

In Indonesia
North Sumatra West Kalimantan North Sulawesi

Irian Jaya

Lampung Jakarta Bali Flores

East Timor

Fig. I. Geographic distribution of in Indonesia until 1995. Areas endemic with taeniasis are indicated in colour. ( Modified from the unpublished report CDC & EH. Ministry of Health, Indonesia, 1983 1996 )

Pathology :3 Form cysticercosis in CNS 1. A cystic form involving the ventricles and brain parenchyma 2. A racemose form involving the meninges 3. A miliary form that is common in children

PATOGENESIS
Human NCC : ingest food contaminated with T.solium egg Parasite survive over period of year It secretes protease inhibitor, taeniastatin that inhibit complement activation, neutrophyl, lymphocyte and cytokine production. Minimal inflammation around viable cyst Inflammatory respons attacks the parasite, leads to degeneration and calcification

CLINICAL MANIFESTATION Number of the cysts Location (parenchimal/spinal) Parasite activity Immune respons of the host

DIAGNOSIS
Definitive Present of the scolex on histologic examination or on CT scan/MRI

MRI
More sensitif for detect parenchymal cyst, intraventricular and subarachnoid cyst

MANAGEMENT NCC Anti parasitic drug Symptomatic and antiinflamatory Surgery

ANTI PARASITIC DRUG

Praziquantel : 50mg/kg/day, two weeks. Albendazol : 15mg/kg/day, one month.

SYMPTOMATIC/ ANTIINFLAMMATION

Corticosteroid :
Dexamethasone 4,5 12 mg/day, or Prednisone 1mg/kg/day. Decrease neurological symptoms due to the death of the parasite. Manitol 2g/kg/day, for acute intracranial hypertension. First line antiepileptic

SURGERY
For excision of large cysts or cyst in the ventricles