CNS Infections. Philip Gothard Consultant in Infectious Diseases Hospital for Tropical Diseases, London. Hammersmith Acute Medicine 2011

Transcription

1 CNS Infections Philip Gothard Consultant in Infectious Diseases Hospital for Tropical Diseases, London Hammersmith Acute Medicine 2011

2 Case 1 HISTORY 27y man Unwell 3 days Fever Headache Photophobia Previously well No travel No head injury

3 Case 1 HISTORY 27y man Unwell 3 days Fever Headache Photophobia Previously well No travel No head injury EXAMINATION T 38.2 P 96 R 18 BP 110/60 GCS 15 Kernig s positive No lateralising signs No rash Normal ENT

4 Q1 What is the next step in your management? 1 CT head 2 Lumbar puncture 3 Antibiotics

5 When is an LP without a CT scan safe? 1959 Neurology 15/129 with RICP signs had bad outcome 2001 Prospective single centre study 301 adults with suspected meningitis 81 had meningitis on LP Risk factors: old or immunosuppressed or abnormal neurology Normal CT Abnormal CT No risk factor or more risk factors Time to antibiotics delayed 3.8 v 2.9 hours, p = 0.09 Hasbun R et al NEJM 2001;345:

6 Q2 What is the most likely pathogen? 1 Enterovirus 2 Haemophilus influenzae 3 Herpes simplex virus 4 Neisseria meningitidis 5 Streptococcus pneumoniae

7 Meningitis: epidemiology UK adult cases N meningitidis 900 S pneumoniae 300 S aureus 40 L monocytogenes 20 M tuberculosis 70 E coli 10 S pyogenes 10 H influenzae 2 Early clinical features do not distinguish viral from bacterial Enterovirus ~10000

8 Meningitis: clinical features 132 Icelandic adults with proven bacterial meningitis Temperature > 38 97% Neck stiffness 82% Abnormal mentation 66% Rash 51% Seizure 10% Papilloedema 4% Sigurdardottir B et al Arch Intern Med 1997;157:425-30

9 Meningitis: pre-hospital antibiotics 47/53 (88%) of patients given pre-hospital antibiotics still had positive CSF +/- blood cultures Wylie PAF et al BMJ 1997;315:774-9 Pre-hospital antibiotics reduced blood culture positives but did not change nasopharyngeal culture rates Sorensen HT et al BMJ 1992:305:774 PCR remains positive for 48 hours after antibiotics but culture negative so no antibiotic sensitivities

10 Meningitis: diagnostic samples Yield Throat swab for urgent Gram s stain 1/2 Rash scraping for urgent Gram s stain 2/3 Urine for pneumococcal antigen 1/3 CSF for urgent Gram s stain 2/3 Blood Cultures 1/2 EDTA (FBC) tube for PCR 9/10 Serum for acute & convalescent serology

11 Q3 Which of the following is not a contra-indication to LP? 1 VII nerve palsy 2 GCS 12 3 BP 80/50 4 INR > 2 5 Purpuric rash

12 Lumbar puncture written consent platelets > 80; INR <2 500 ml total CSF 100 ml - daily production 10 ml measure OP & CP send for urgent Gram s stain (3/4 positive) GIVE ANTIBIOTICS IF MORE THAN 30 MINUTE DELAY

13 Q4 In severe penicillin allergy which antibiotic is used? 1 Ceftriaxone 2 Ciprofloxacin 3 Meropenem 4 Tazocin 5 Vancomycin

14 Q5 If the patient s conscious level deteriorates 1 Urgent CT head 2 Activated Protein C 3 Mannitol 4 Add Chloramphenicol

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16 Meningitis: what is the prognosis? Bad signs Age > 60 Bleeding Multi-organ failure Focal neurological signs Falling GCS In 100 patients with any form of meningitis GCS > 12 GCS < 8 90% good outcome 90% bad outcome Schutte CM et al J Infect 1998;37:112-5

17 Q6 Dexamethasone improves survival in bacterial meningitis and should be given with the first dose of antibiotic. 1 True 2 False

18 Steroids in bacterial meningitis multi-centre RCT 301 patients Dexamethasone 10mg QDS with first dose antibiotic morbidity mortality RR 0.59 (CI ) p=0.03 RR 0.48 (CI ) p= /58 v 26/50 NNT = 4 (p=0.006) reduction in systemic deaths in Pneumococcal group de Gans-J et al NEJM (2002);347:

19 Steroids in bacterial meningitis European study (NEJM 2002) Vietnam study (NEJM 2009) Malawi study (NEJM 2009) Yes Possibly No British Infection Society guidelines Consider Meta-analysis (Lancet Neurology 2010) No

20 Case 2 History 48y black man BIBA Found semi-conscious on bed Surrounded by beer cans No further info available Examination Dehydrated T 34.6 P 110 R 20 BP 92/60

21 Q7 what is the most important test? 1Blood alcohol level 2Blood culture 3Blood film (for malaria) 4Blood glucose 5Blood lactate

22 Case 2: initial management Assessment Cachectic GCS 10; otherwise normal neurology No stigmata of chronic liver disease Bronchial breathing R lung base Management IV fluids Bear hugger Urinary catheter Antibiotics

23 Q8 What is the most likely diagnosis? 1 Advanced HIV infection 2 Bacterial meningitis 3 Disseminated tuberculosis 4 Hepatic encephalopathy 5 HSV encephalitis

24 Case 2: more information... History From Mozambique Long history of binge drinking Usually high intellectual function Tests Urea 15 Hb 17.4 Cr 128 WCC 10.7 Na 146 Plts 72 K 3.4 CRP 30 venous lactate 5.6 CXR: R lower lobe pneumonia

25 Case 2: more information Unenhanced CT Normal Treatment Ceftriaxone 2g BD LP OP 22 cmh 2 O Protein 0.56 g/dl Glucose 2.2 mmol/l (blood 4.6) Red cells 98 /ml White cells 13 /ml (mononuclear)

26 Q9 which diagnosis is excluded now? 1 Advanced HIV infection 2 Bacterial meningitis 3 Disseminated tuberculosis 4 Hepatic encephalopathy 5 HSV encephalitis

27 Differential is still wide: what next? CSF samples India Ink stain PCR for Herpes & Enterovirus PCR and culture for TB Culture for bacteria Extra-neural clues CXR Urine antigens Respiratory viruses (influenza) Epidemiological info HIV status Recent travel and activities

28 Encephalitis: causes Causes California Project Viral culture Unknown Enterovirus HSV West Nile (US) Other herpes viruses Long list of very very rare (Rabies) extensive investigation 2/3 no diagnosis (208/334) 1/20 positive (of 22,394 samples) 98% enterovirus Glaser ClD 2003 & Polage CID 2006

29 Encephalitis: MRI scan HSV Enterovirus temporal lobe brainstem ADEM multi-focal (cf encephalitis) enhancing lesions (cf PMLE) white and grey matter (cf multiple sclerosis) Note MRI diffusion-weighted best early EEG non-specific; discordant with clinical

30 HSV encephalitis Rare Diagnosis Outcome Poor prognosis Treatment UK 100 cases / y PCR 97%+ sensitivity & specificity repeat if suspicious 25% mortality with treatment older age low GCS prolonged symptoms 2 3 weeks continue if PCR+ at 21d

31 Q10: HIV+. What is the most likely diagnosis? 1.Cryptococcal meningitis 2.HSV encephalitis 3.Pneumococcal meningitis 4.TB meningitis 5.Toxoplasmosis

32 CNS Infections: summary 1. Most fever and headache is not meningitis 2. Most meningitis is not bacterial 3. Most viral meningitis is not HSV 4. No evidence for steroids in bacterial meningitis 5. Encephalitis is not meningitis 6. Detailed risk history is important 7. HSV is rare, serious and treatable 8. All patients should be offered an HIV test 9. TB meningitis is often missed

33 Post-exposure prophylaxis Phone CCDC yourself and make a list of contacts In first 24 hours give Rifampicin or Ciprofloxacin to 1 week household and kissing contacts Staff at high risk Patient Warn contacts highest risk (1000x) in first week but < 1/200 absolute risk increased risk for 6 /12 despite prophylaxis inform GP Consider vaccination