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 9 CRP 123 Electrolytes normal MSU: wcc 32 Next…..

Case 1 CT brain normal LP: – 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 positive MRI 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 normal Febrile T 38.4 when returns from CT LP: – wcc % PMN, 30% lymphocytes – rcc 4 – Protein 0.48 g/l – Glucose 3.2

Case 2 Diagnosis?

Case 2 No antibiotics given Admitted for analgesia, hydration Recovered quickly, home Monday morning Enterovirus PCR negative

Case 3 16yo boy Presents 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 8 LFT, U+E normal CRP 300

Case 3 Differential diagnosis? What next?

Case 3 Sent home with analgesia, GP letter 36 hrs later bld cultures flagged positive for GPC What to do?

Case 3 Patients parents called. Instructed to present to GP GP referred back to ED On arrival still headache, oriented CRP 330 Referred to medical team ?LP CT 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 Admitted CT changed to report sphenoid sinusitis Antibiotics with-held ? Viral 24 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 presentation Onset of illness – Patients often feel very unwell early and present within hours of onset Average time to presentation <24hrs Severe myalgias indicate bacterial sepsis More unwell than patients with viral meningitis: drowsy, pale, hypotension, tachycardia.

Bacterial meningitis - diagnosis CSFBacterial meningitis Viral meningitis Cell count (<4 LØ/mL) >1000<500 Differential>90% PMNLØ predom (may be PMN early) Protein ( g/L) > Glucose (2/3 of serum) DecreasedNormal

Aetiology Neisseria meningitidis – Children and young adults Streptococcus pneumoniae – All ages Listeria monocytogenes – Infants and elderly Haemophilus influenzae type B

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: SENSINTRES ≤0.51≥2 mcg/mL Ceftriaxone levels approx in CSF

Listeria meningitis 2nd most common cause of bacterial meningitis in adults >50 Even more common if immunosuppressed Can produce meningoENCEPHALITIS Can be culture negative Resistant to cephalosporins, sensitive to penicillin

Listeria meningoencepalitis

Management of possible bacterial meningitis Focus is ensuring rapid administration of treatment whilst attempting diagnosis – Lumbar puncture – Antibiotics – Corticosteroids – CT brain

Management of possible bacterial meningitis Delay 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 meningitis Factors 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 meningitis Is 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: Immunosuppressed Age >60 Focal 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 meningitis Sequence of management either: 1. LP then abx OR 2. Abx then CT then LP NOT CT then LP then abx

Management of possible bacterial meningitis Corticosteroids? – 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 meningitis Empiric antibiotics – Ceftriaxone 2g 12 hourly (S.pneumo, N.meningitidis) – Benzylpenicillin 2.4g 4 hourly (listeria) – Vancomycin (high dose, aim levels ) (ceftriaxone/pen resistant S.pneumo) – Other Moxifloxacin? Rifampicin?

Viral meningitis

Enteroviruses Not as unwell (no hypotension, no decreased conscious state) Self limited But it does hurt! CSF Enterovirus PCR

Viral meningitis CSFBacterial meningitis Viral meningitis Cell count (<4 LØ/mL) >1000<500 Differential>90% PMNLØ predom (may be PMN early) Protein ( g/L) > Glucose (2/3 of serum) DecreasedNormal

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

Result from sinusitis – Mastoid, frontal most common – Sphenoid and ethmoid more difficult to diagnose Osteomyelitis -> epidural -> subdural - > brain abscess Suspect when history of sinus symptoms then worsening headache

Cranial parameningeal infections Diagnose with imaging – Need MRI for ethmoid/sphenoid sinuses CSF variable. Increased wcc 15- to >1000 Management: – Broad spectrum abx covering S.aureus, Strep, anaerobes – Urgent surgical referral

Encephalitis

Focal neurological signs, seizure, confusion, decreased conscious state Can be some headache but this isn’t the primary symptom +/- fever

Encephalitis HSV-1 Wide-spectrum of other viruses and microorganisms – MVE, West-Nile, Nipah Listeria Many go undiagnosed

CSF with encephalitis CSFEncephalitisBacterial meningitis Viral meningitis Cell count (<4 LØ/mL) <100>1000<500 DifferentialLØ predom>90% PMNLØ predom (may be PMN early) Protein ( g/L) Normal to slight incr >1Normal to slight incr (<1) Glucose (2/3 of serum) NormalDecreasedNormal

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

HSV encephalitis iv aciclovir Prognosis 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