CNS Infections EMERGENCY NEUROLOGY LECTURE SERIES

 

August 24, 2011

Dr. Abdullah Al-Salti R4

CNS Infections Case scenario

Bacterial meningitis . C.T before L.P Dexamethasone used Prophylaxes.

Viral encephalitis

L.P procedure.

CASE 1

A 21-year-old college student was found poorly responsive in her room. She had complained of a headache for about 4 days that was refractory to NSAIDs.

In the ER, temperature was 39.5°C, with BP 145/100 mmHg, HR of 112 per minute and RR of 18 per minute.

She partly responded to verbal commands, localized symmetrically to noxious stimuli, and moaned incoherently.

Neurological examination showed nuchal rigidity, and normal brainstem reflexes, with symmetric hyperreflexia and flexor plantar responses.

CASE 1

H.P.IONSET,

COURSE ,DURATION

CONSTITIUSIONAL SYMPTOMES.

SCREEN NUEROLOGICAL

SYSTEMS.

SYSTEMIC REVIEW.

WHAT IS SO FARE BEEN DONE ?

First thing to do

PMH.

SURGICAL HISTORY

MEDICATIONS.

FAMILY HISTORY.

HABITES.

SOCIAL .

Examination :1. Focal neurological deficitst .

2. Signs of meninegeal irritation.

3. Signs of raised ICP.

4. General systemic exam.

Ddx:?

Investigasion ?

Treatments?

CNS INFECTIONS

CNS INFECTIONSOverview

Life-threatening problems with high associated mortality and morbidity.

Presentation may be acute, subacute, or chronic.

Clinical findings determined by anatomic site(s) of involvement, infecting pathogen, and host response.

Vulnerability of CNS to the effects of inflammation & edema mandates prompt diagnosis with appropriate therapy if consequences to be minimized.

CNS InfectionsMeningitis

Bacterial, viral, fungal, chemical, carcinomatous

EncephalitisBacterial, viral

Meningoencephalitis

AbscessParenchymal, subdural, epidural

INFECTIONS 4 routes which infectious agents can enter the CNS

a) hematogenous spreadi) most common

- usually via arterial route- can enter retrogradely (veins)

b) direct implantationi) most often is traumaticii) iatrogenic (rare) via lumbar punctureiii) congenital (meningomyelocele)

c) local extension (secondary to established infections) i) most often from mastoid, frontal sinuses, infected

tooth, etc.d) PNS into CNS

i) viruses- rabies- herpes zoster

BACTERIAL MENINGITIS

Meningitis

refers to an inflammatory process of leptomeninges and CSF.

Meningoencephalitis

refers to inflammation to meninges and brain parenchyma.

Meningitis classified:

a) acute pyogenic i) usually bacterial meningitis

b) aseptici) usually acute viral meningitis

c) chronici) usually TB, spirochetes, cryptococcus.

Incidence of 3 cases/100,000 population/yr (~25,000 total cases).

COMMON BACTERIAL PATHOGENS BASED ON PREDISPOSING FACTOR IN PATIENTS WITH MENINGITIS

Predisposing Factor

Age

0-4 wK

4-12 wk

3 mo to 18 yr

18-50 yr

>50 yr

Common Bacterial Pathogens

Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella pneumoniae, Enterococcus spp., Salmonella spp.

S. agalactiae, E. coli, L. monocytogenes, Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis

H. influenzae, N. meningitidis, S. pneumoniae

S. pneumoniae, N. meningitidis

S. pneumoniae, N. meningitidis, L..monocytogenes, aerobic gram-negative bacilli

Clinical Features

Signs and symptoms:

rapid onset of fever

headache

photophobia

nuchal rigidity

lethargy, malaise

altered mentation

seizure

vomiting.

van de Beek D, de Gans J, Tunkel AR, et al. Community-acquired bacterial meningitisin adults. N Engl J Med 2006;354(1):44–53.

Clinical Features Study of 493 adult patients with bacterial meningitis,

the presence of the ‘‘classic triad’’ of

fever, neck stiffness, and altered mental status was present in two-thirds of patients.

fever WAS the most common element, in 95%.

(N Engl J Med 1993;328(1):21–8. )

Older patients with S. pneumoniae meningitis are more likely to have the classic triad.

Weisfelt M, van de Beek D, Spanjaard L, et al. Community-acquired bacterial meningitis in older people. J Am Geriatr Soc 2006;54(10):1500–7.

Physical examinationA careful neurological examination is important

to evaluate for :

focal deficits increased intracranial pressure (ICP).

Examination should include assessment for meningeal irritation Brudzinski’s sign Kernig’s sign

findings include purpura or petechia of the skin, which may occur with meningococcemia.

(straightening of the knee with a flexed hip resulting in back and neck pain)

(passive flexion of the neck resulting in flexion of the hips and knees)

Bacterial meningitis

Investigations

LPSingle most impt diagnostic test.

Mandatory, esp if bacterial meningitis suspected.

Tube #1 – glucose and protein

Tube #2 – cell count and differential

Tube #3 – gram stain and rountine culture, cyrptococcal antigen, AFB stain and culture

Tube #4 – VDRL, or viral studies (PCR)

CSF CharacteristicsBacterialBacterial ViralViral FungalFungal TBTB

Opening Opening PressurePressure

ElevatedElevated Slight Slight elevatedelevated

Normal Normal or Highor High

Usually Usually highhigh

GlcGlc LowLow NormalNormal LowLow LowLow

ProPro Very Very highhigh

NormalNormal HighHigh HighHigh

RbcsRbcs FewFew NoneNone NoneNone NoneNone

Wbcs Wbcs (c/mm3)(c/mm3)

>>200200 <<200200 <<5050 20-3020-30

DiffDiff PMNsPMNs MonoMono MonoMono MonoMono

CT Before LP in Patients with Suspected Meningitis

301 pts with suspected meningitis; 235 (78%) had CT prior to LP

CT abnormal in 56/235 (24%); 11 pts (5%) had evidence of mass effect

Features associated with abnl. CT were:

age >60, immunocompromise, H/O CNS dz, H/O seizure w/in 7d, & selected neuro abnls

Hasbun, NEJM 2001;345:1727

CT head Before LP(Cont.)

96/235 pts (41%) who underwent CT had none of features present at baseline

CT normal in 93 of these 96 pts (NPV 97%).

Of the 3 remaining patients, only 1 had mild mass effect on CT, and all 3 underwent lumbar puncture with no evidence of brain herniation

Hasbun, NEJM 2001;345:1727

Consideration for lumbar puncture without

neuroimagingDavid Somand, MDa,WilliamMeurer, MD

Department of Emergency Medicine, University of Michigan, Taubman Center B1354

SPC #5303, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5303, USA

Age less than 60.

Immunocompetent.

No history of CNS disease.

No recent seizure (less than 1 week).

Normal sensorium and cognition.

No papilledema.

No focal neurologic defecits.

BACTERIAL MENINGITIS

Managements

APPROACH TO THE PATIENT WITH SUSPECTED MENINGITIS

Decision-Making Within the First 30 Minutes

Clinical AssessmentClinical Assessment

Mode of presentationMode of presentation Acute (< 24 hrs)Acute (< 24 hrs) Subacute (< 7 days)Subacute (< 7 days) Chronic (> 4 wks)Chronic (> 4 wks)

Historical/physical exam cluesHistorical/physical exam clues Clinical status of the patient (ABCD)Clinical status of the patient (ABCD)

Integrity of host defensesIntegrity of host defenses

Management algorithm for adults with suspected bacterial meningitis.

Practice Guidelines for the Management of Bacterial Meningitis

BACTERIAL MENINGITISAntimicrobial Rx

Therapy is generally IV, high dose, & bolus.

Dosing intervals should be appropriate for drug being administered.

Utilize “cidal” therapy whenever possible.

Initiate therapy promptly (ie, within 30 mins)

THE THERAPY OF MENINGITISCNS Penetration

Good Diffusion Penicillins 3rd & 4th Gen Cephs Chloramphenicol Rifampin TSX

Poor Diffusion Early Gen Cephs Clindamycin AMGs Tetracyclines Macrolides

EMPIRIC THERAPY OF MENINGITIS IN THE ADULT

Clinical Setting Likely Pathogens Therapy

Community-acquired S. Pneumoniae

N. meningitidis

[Listeria]

[H. influenzae]

Ceftriaxone

2 gm

q12h

+

Vancomycin 1-2 gm

12h

+/_

Ampicillin 2 gm q4h

EMPIRIC THERAPY OF MENINGITIS IN THE ADULT

Closed head trauma S. pneumoniae Pen G 3-4 mu q4h

Streptococci +

Vancomycin 1-2 gm q12h

EMPIRIC THERAPY OF MENINGITIS IN THE ADULT

Clinical Setting Likely Pathogens Therapy

High risk patients S. aureus Vancomycin 2-3 gm/d

Compromised hosts Gram negative +

Neurosurgical bacilli Ceftazidime 2 gm q8h or

Open head injury Listeria Cefepime 2 gm q8h

Nosocomial [Ceftriaxone 2 gm q12h]

Elderly [Cefotaxime 2 gm q4h]

+/-

Ampicillin 2 gm q4h

BACTERIAL MENINGITISDuration of ATB Rx

Pathogen Duration of Rx (d)

H. influenzae 7

N. meningitidis 7

S. pneumoniae 10-14

L. monocytogenes 14-21

Group B strep 14-21

GNRs 21

NEJ1997;336:708

CORTICOSTEROIDS AND MENINGITIS

Recent European study in adults suggested that Rx with dexa associated with ↓ in risk of unfavorable outcome (25%→15%, RR 0.59) & in mortality (15%→7%, RR for death 0.48).

Benefit primarily pts w/S. pneumo.

Dose of dex was 10mg IV q6h X 4d; per protocol, dex given concurrent with or 15-20 mins before 1st dose of ATBs.

Acute bacterial meningitis Antibiotic prophylaxis

Is recommended for high-risk exposures to patients with Neisseria or Hib meningitis.(potentially share secretions).

Regimens include :Single-dose ciprofloxacin or ceftriaxone.Rifampin 600 mg every 12 hours for five doses.

There is no indication for prophylaxis for exposure to pneumococcal meningitis.

Quinolone resistance has been reported to Neisseria, and this class of antibiotics is no longer recommended for prophylaxis in parts of the United States.

PREDICTORS OF ADVERSE CLINICAL OUTCOMES IN PTS WITH COMMUNITY-

ACQUIRED BACTERIAL MENINGITIS Aronin et al, AIM1998;129:862

Retrospecitve study; 269 pts (84% culture +).

Adverse clinical outcome in 36% of pts(Death 27%, neuro deficit 9%).

↓BP, altered MS, and seizures on presentation all independently associated with adverse clinical outcome.

Adverse outcomes in 5% of low risk pts (0 features), 37% of intermediate risk pts (1 feature), and 63% of high risk pts (2-3 features).

Delay in administration of appropriate ATB Rx also associated with adverse clinical outcome.

Viral MeningitisVery common• clinical course is less fulminant compared to

bacterial

Often caused by enteroviruses

Polioviruses Coxsackieviruses Echoviruses

Treatment is supportive

VIRAL ENCEPHALITIS

IntroductionEncephalitis is an acute inflammatory process

affecting the brain

Viral infection is the most common and important cause, with over 100 viruses implicated worldwide

Symptoms Fever Headache Behavioral changes Altered level of consciousness Focal neurologic deficits Seizures

Incidence of 3.5-7.4 per 100,000 persons per year

VIRAL ENCEPHALITISEnteroviruses

Polioviruses

Coxsackieviruses

Echoviruses

Togaviruses

Eastern equine

Western equine

Venezuelan equine

St. Louis

Powasson

California

West Nile

Herpesviruses

Herpes simplex

Varicella-zoster

Epstein Barr

Cytomegalovirus

Myxo/paramyxoviruses

Influenza/parainfluenzae

Mumps

Measles

Miscellaneous

Adenoviruses

LCM

Rabies

HIV

Patient HistoryDetailed history critical to determine the likely cause of

encephalitis.

Prodromal illness, recent vaccination, development of few days → Acute Disseminated Encephalomyelitis (ADEM) .

Biphasic onset: systemic illness then CNS disease → Enterovirus encephalitis.

Abrupt onset, rapid progression over few days → HSE.

Recent travel and the geographical context: Africa → Cerebral malaria Asia → Japanese encephalitis High risk regions of Europe and USA → Lyme disease

Recent animal bites → Tick borne encephalitis or Rabies.

Occupation Forest worker, exposed to tick bites Medical personnel, possible exposure to infectious diseases.

History cont.Season

Japanese encephalitis is more common during the rainy season.

Arbovirus infections are more frequent during summer and fall.

Predisposing factors: Immunosuppression caused by disease and/or drug

treatment. Organ transplant → Opportunistic infections HIV → CNS infections HSV-2 encephalitis and Cytomegalovirus infection (CMV)

Drug ingestion and/or abuse

Trauma

Initial SignsHeadache

Malaise

Anorexia

Nausea and Vomiting

Abdominal pain

Developing SignsAltered LOC – mild lethargy to deep coma.

AMS – confused, delirious, disoriented.

Mental aberrations: hallucinationsagitationpersonality change behavioral disorders occasionally frank psychosis

Focal or general seizures in >50% severe cases.

Severe focused neurologic deficits.

Neurologic SignsVirtually every possible focal neurological

disturbance has been reported.

Most CommonAphasiaAtaxia Hemiparesis.Involuntary movementsCranial nerve deficits (ocular palsies, facial

weakness)

Other Causes of Encephalopathy

Anoxic/Ischemic conditions

Metabolic disorders

Nutritional deficiency

Toxic (Accidental & Intentional)

Systemic infections

Critical illness

Malignant hypertension

Mitochondrial cytopathy (Reye’s and MELAS syndromes)

Hashimoto’s encephalopathy

Traumatic brain injury

Epileptic (non-convulsive status)

CJD (Mad Cow)

Differential Diagnosis

Distinguish Etiology

(1) Bacterial infection and other infectious conditions (2) Parameningeal infections or partially treated

bacterial meningitis (3) Nonviral infectious meningitides where cultures may

be negative (e.g., fungal, tuberculous, parasitic, or syphilitic disease)

(4) Meningitis secondary to noninfectious inflammatory diseases

VIRAL ENCEPHALITIS

DIAGNOSIS.

LP:

CSF usually colorless

- slightly pressure

- initially a neutrophilic pleocytosis, which rapidly converts to lymphocytes

- proteins are

- glucose is normal

PCR for HSE and other viral infection is diagnostic .

VIRAL ENCEPHALITISDIAGNOSIS.

MRI:

May show temporal or orbitofrontal cortex enhancement or edema in HSE.

In most other acute viral encephalities , neuroimaging finding are nonspecific.

Can exclude subdural bleeds, tumor, and sinus thrombosis.

EEG: Non specific Diffuse slowing . Focal abnormalities in the temporal region . HSV

Treatment. Only HSV disease has specific therapy available. Acyclovir

is capable of improving patient outcome.

dose : 10 mg/kg intravenously every 8 hours. Duration 14-21 days.

ganciclovir can be used in CMV infections. pleconaril has shown promise in enteroviral.

Outcomes

Outcomes are variable depending on etiology.

EEE and St. Louis encephalitis generally have high mortality rates and Severe neurologic sequelae among survivors.

WNV is associated with significant morbidity and morality.

Mortality of HSV encephalitis before acyclovir was 60% to 70%, and with treatment approximately 30%.

Cognitive disability,seizures, and motor deficits are common sequelae seen among survivors