Central nervous system infections

3 quick cases….

Case 1

67 yo woman Past history

– Type 2 DM– HT

Presented to ED via ambulance– called by daughter (who lives in Frankston)

Difficult historian– On questioning says has had headaches for 2

days– Lethargy, anorexia

Case 1

On examination– Drowsy but eye opens to voice– Disoriented to time but not place– Febrile T 37.8– Chest clear– FWT leucocyte, nitrite positive

Case 1

Differential diagnosis?

Case 1

Daughter noticed patient to be ‘vague’ and saying strange things over the phone last 4 days

Didn’t mention to daughter about headache

Telephoned her at 3.30 am that morning asking her where her cat was

Case 1

FBE: wbc 12, PMN 9CRP 123Electrolytes normalMSU: wcc 32

Next…..

Case 1

CT brain normalLP:

– wcc 15, 100% lymphocytes– rcc 3– Protein 0.35 g/l– Glucose normal

Case 1

Diagnosis?

Case 1

After d/w ID started on iv aciclovir and benzylpenicillin

2 days later HSV PCR on CSF positiveMRI brain:

HSV encephalitis

Case 2

27 yo female Brought in to ED 10pm Saturday night by

boyfriend Complaining of severe headache, present 2

days. Supposed to go to Sydney for the weekend but cancelled Friday because ‘felt like crap’. Assoc nausea, lethargy.

Feeling hot and flushed

Case 2

Examination– Lying curled up in dark cubicle– Not opening her eyes when talking to you

but able to answer all questions– Got up to go to toilet just after seen– T 36.8– Pulse 88, BP 115/80– Warm, well perfused

Case 2

Differential diagnosis?What next?

Case 2

CT brain normalFebrile T 38.4 when returns from CTLP:

– wcc 32070% PMN, 30% lymphocytes

– rcc 4– Protein 0.48 g/l– Glucose 3.2

Case 2

Diagnosis?

Case 2

No antibiotics givenAdmitted for analgesia, hydrationRecovered quickly, home Monday

morningEnterovirus PCR negative

Case 3

16yo boyPresents with 5 day history of

headaches, fevers‘Bad’ headaches. Some relief with

paracetamol but getting worse so presented to ED

URTI week prior but this resolved mostly

Case 3

On examination alert and oriented, no neck stiffness. No neuro signs. Febrile T38.1

FBE: wbc 11, PMN 8LFT, U+E normalCRP 300

Case 3

Differential diagnosis?What next?

Case 3

Sent home with analgesia, GP letter36 hrs later bld cultures flagged

positive for GPCWhat to do?

Case 3

Patients parents called. Instructed to present to GP

GP referred back to EDOn arrival still headache, orientedCRP 330Referred to medical team ?LPCT brain performed, reported as

normal

Case 3

LP– wcc 8

100% PMN– rcc 1– Prot 0.38– Gluc normal

Case 3

Significance of this result?

Case 3

AdmittedCT changed to report sphenoid

sinusitisAntibiotics with-held ? Viral24 hours after admission:

– decreased conscious state– ARDS– ICU

Bld cultures: Strep milleri

Case 3

Despite broad-spectrum antibiotics and ENT surgery pt deteriorated

CNS infections

Headache– Meningitis– Para-meningeal infection

Confusion/seizure/focal signs– Encephalitis– Brain abscess

**History of symptoms at beginning of illness and duration crucial in differential diagnosis

Meningitis

Acute meningitis– Bacterial– Viral

‘Chronic’ meningitis– Tuberculosis– Fungal (Cryptococcal)– Non-infectious (malignant, sarcoid)

Acute bacterial meningitis

Bacterial meningitis clinical presentation HEADACHE

– Severe– Can be sudden onset– Rapidly worsens

Fever– Sometimes afebrile/hypothermia– History of fever (v’s making diagnosis based on

temperature on arrival in ED) Neck stiffness common but not sensitive

enough to exclude dgx

Bacterial meningitis clinical presentationOnset of illness

– Patients often feel very unwell early and present within hours of onsetAverage time to presentation <24hrs

Severe myalgias indicate bacterial sepsis

More unwell than patients with viral meningitis: drowsy, pale, hypotension, tachycardia.

Bacterial meningitis - diagnosis

CSF Bacterial meningitis

Viral meningitis

Cell count(<4 LØ/mL)

>1000 <500

Differential >90% PMN LØ predom (may be PMN early)

Protein (0.2-0.4g/L)

>1 0.4-1

Glucose (2/3 of serum)

Decreased Normal

Aetiology

Neisseria meningitidis– Children and young adults

Streptococcus pneumoniae– All ages

Listeria monocytogenes– Infants and elderly

Haemophilus influenzae type B

N.meningitidis

0

100

200

300

400

500

600

700

1999 2001 2003 2005 2007

meningoccocalnotifications australia

N.meningitidis

S.pneumoniae – CSF and blood culture isolate penicillin sens

Beta-lactam resistant S.pneumoniae Penicillin MIC:

SENS RES≤0.06 ≥0.12 mcg/mL

Penicillin levels approx 0.5 in CSF

Ceftriaxone MIC:SENS INT RES ≤0.5 1 ≥2 mcg/mL

Ceftriaxone levels approx 0.5-4 in CSF

Listeria meningitis

2nd most common cause of bacterial meningitis in adults >50

Even more common if immunosuppressed

Can produce meningoENCEPHALITISCan be culture negativeResistant to cephalosporins, sensitive

to penicillin

Listeria meningoencepalitis

Management of possible bacterial meningitisFocus is ensuring rapid administration

of treatment whilst attempting diagnosis– Lumbar puncture– Antibiotics– Corticosteroids– CT brain

Management of possible bacterial meningitisDelay in antibiotics leads to greater

mortality and worse neurological outcome– Delay >3hrs from time of arrival: mortality

OR 14 (Auburtin et al, Crit Care Med. 2006)

Management of possible bacterial meningitisFactors associated with delay in

antibiotics– Afebrile at presentation– Triage to physician time– Time from LP to abx– CT brain!!

Sequence of CT then LP then abx

Management of possible bacterial meningitisIs a CT brain required before LP in

adults with suspected meningitis?– 5% of patients will have mass effect– All of those with significant mass effect:

ImmunosuppressedAge >60Focal neuro/seizures/decreased

consciousness/papilloedema– In the absence of these features safe to

perform LP without CT brain(Hasbun NEJM 2001)

Management of possible bacterial meningitisSequence of management either:

1. LP then abxOR2. Abx then CT then LP

NOT CT then LP then abx

Management of possible bacterial meningitisCorticosteroids?

– Dexamethasone 10mg 6hrly 4 days– Started just prior to abx– Possibly not effective if started later– Reduction in mortality from 34% to 14%

Mostly from S.pneumoniae group(de Gans et al NEJM 2002)

Management of possible bacterial meningitisEmpiric antibiotics

– Ceftriaxone 2g 12 hourly (S.pneumo, N.meningitidis)

– Benzylpenicillin 2.4g 4 hourly (listeria)– Vancomycin (high dose, aim levels 20-

30) (ceftriaxone/pen resistant S.pneumo)

– Other Moxifloxacin? Rifampicin?

Viral meningitis

Viral meningitis

EnterovirusesNot as unwell (no hypotension, no

decreased conscious state)Self limitedBut it does hurt!CSF Enterovirus PCR

Viral meningitis

CSF Bacterial meningitis

Viral meningitis

Cell count(<4 LØ/mL)

>1000 <500

Differential >90% PMN LØ predom (may be PMN early)

Protein (0.2-0.4g/L)

>1 0.4-1

Glucose (2/3 of serum)

Decreased Normal

Viral meningitis

There is a differential diagnosis of ‘sterile’ meningitis with acute presentation– Tb, cryptococcal– Parameningeal infections– HIV, mumps, rat-lungworm

Measure pressure and get plenty of CSF (most people can tolerate 10-20ml). Lots of tests to do!

Cranial parameningeal infections

Cranial parameningeal infectionsResult from sinusitis

– Mastoid, frontal most common– Sphenoid and ethmoid more difficult to

diagnoseOsteomyelitis -> epidural -> subdural -

> brain abscessSuspect when history of sinus

symptoms then worsening headache

Cranial parameningeal infectionsDiagnose with imaging

– Need MRI for ethmoid/sphenoid sinusesCSF variable. Increased wcc 15- to

>1000 Management:

– Broad spectrum abx covering S.aureus, Strep, anaerobes

– Urgent surgical referral

Encephalitis

Encephalitis

Focal neurological signs, seizure, confusion, decreased conscious state

Can be some headache but this isn’t the primary symptom

+/- fever

Encephalitis

HSV-1Wide-spectrum of other viruses and

microorganisms– MVE, West-Nile, Nipah

ListeriaMany go undiagnosed

CSF with encephalitis

CSF Encephalitis Bacterial meningitis

Viral meningitis

Cell count(<4 LØ/mL)

<100 >1000 <500

Differential LØ predom >90% PMN LØ predom (may be PMN early)

Protein (0.2-0.4g/L)

Normal to slight incr

>1 Normal to slight incr (<1)

Glucose (2/3 of serum)

Normal Decreased Normal

HSV Encephalitis

HSV PCR very sensitive and specific. Can be negative early in course of disease

HSV encephalitis

iv aciclovirPrognosis depends on degree of

impairment at presentation

Brain abscess

Focal signs, fever and headache Presentation often more prolonged

– Days to weeks– But can present with eg seizure in previously well

person Source

– Contiguous– Haematogenous: lung abscess, dental

Strep milleri group, S.aureus

Management: surgery and prolonged abx

Central nervous system infections Precise history essential to diagnosis CSF findings very helpful in confirming

diagnosis Medical (or surgical) emergency

– Prioritise patients and act quickly– When suspect bacterial meningitis don’t let

imaging delay therapy Don’t forget steroids and vanc for bacterial

meningitis Call ID team!!

Ms IN

Cellulitis RCT at TNH

Trial of iv abx versus oral abx for cellulitis at The Northern.

Refer any patient in whom you would consider iv abx (even 1 dose or even if you aren’t sure)– Can be planned for inpatient stay or ready for

discharge– Don’t try to look for inclusion or exclusion

criteria yourself.– If patient accepted then we take over

management