CNS Infec*ons. Leonard Sowah, MBChB, MPH, FACP

Transcription

1 CNS Infec*ons Leonard Sowah, MBChB, MPH, FACP

2 Overview Epidemiology and risk factors of CNS infec*ons Diagnosis and clinical evalua*on, treatment and sequelae of common CNS infec*ons, meningi*s, encephali*s Two cases of CNS infec*ons Cerebrospinal Fluid Analysis

3 CNS Infec*ons Infec&on of the central nervous system is classified by loca&on. Meningi*s Encephali*s Cerebral Abscess

4 Meningi*s Defini&on Meningi&s is an inflamma&on of the meninges. This inflamma&on is usually caused by an infec&on of the CSF.

5 Epidemiology A study done between suggests 4100 cases of bacterial meningi*s annually Mortality rate based on that data was 13% Of the deaths 70.7% of the cases were Strep. pneumoniae Rates of bacterial meningi*s caused by H. influenzae, S. pneumoniae, Group B Strep, Listeria monocytogenes and N. meningi*dis decreased in the past decade. Thigpen MC et al. N Engl J Med 2011;364:

6 Risk Factors Age >60 years Diabetes mellitus Chronic kidney disease Immunosuppression HIV infec*on Ins*tu*onal living ENT or Dental infec*on Intravenous (IV) drug abuse Bacterial endocardi*s VP shunt Malignancy Alcoholism and cirrhosis Splenectomy and sickle cell disease

7 Anatomy of Brain

8 Classifica*on of Meningi*s Bacterial (pyogenic) Tuberculosis Fungal Granulomatous Asep*c

9 Common Pathogens All ages Haemophilus influenzae - 7 % Strep. pneumoniae - 61 % Neisseria meningi*dis 19% Strep Group B - 3% Listeria monocytegenes 2% Other bacteria - 15%! 1 yr - Strep Group B, Listeria and E. coli! 2mths 4 yrs Neisseria meningi*dia, Strep. Pnemoniae! 5 29 yrs Neisseria meningi*dis! Strep pneumoniae (37%)! > 60 yrs - Strep pneumoniae (48%), Listeria monocytegenes (14%) CLINICAL MICROBIOLOGY REVIEWS, July 2010, p

10 Pathophysiology CLINICAL MICROBIOLOGY REVIEWS, Apr. 1993, p

11 Blood brain barrier in Meningi*s

12 Proportions of the 1670 Cases of Bacterial Meningitis Reported in Caused by Each Pathogen, According to Age Group. Thigpen MC et al. N Engl J Med 2011;364:

13 Symptoms and signs Fever - 77% Headache - 87 % A s*ff neck (usually) - 83% Altered Mental Status - 69% Photosensi*vity Seizures Nausea Bruzinski sign Kernigs sign hhps:// N Engl J Med 2004;351(18):

14 Evalua*on of a pa*ent with suspected CNS infec*on Full history and physical exam Dura*on of symptoms is important CNS exam Cranial Nerves, Motor & MMSE Evalua*on must be focused on looking for signs of increased intracranial pressure ENT exam important to look for primary source Hearing tes*ng to get baseline Extra-ocular movement and visual acuity

15 CT scan Useful if concerning for increased intracranial pressure May be considered if there is focal neurologic deficit to rule out abscess and other space occupying lesions

16 CSF Analysis Normal CSF Characteris*s " Color Clear " Opening Pressure 9-18 cm H 2 O " ph " Glucose mg/dl " Proteins mg/dl " Proteins may be higher in infants " LDH 0 50U/L " WBC - < 10/mm3 Color Cloudy, milky and turbid suggest infec*on Xanthochromic suggest hemorrhage, increased bilirubin Clot May suggest increased protein or TB meningi*s Opening Pressure Increased in fungal and TB meningi*s

17 CSF Analysis Biochemistry Low glucose sugges*ve of bacterial infec*on, fungal and TB( normally % of serum glucose) LDH Elevated in bacterial, TB and fungal meningi*s Protein High in bacterial, fungal and TB and normal or high in viral meningi*s? Trauma*c tap? 1.1 mg/dl for every 1000 RBCs IgG index Oligoclonal bands

18 CSF Analysis CSF for Culture CSF for AFBs if TB is suspected and Indian ink stain if Cryptococcus is suspected Blood Cultures PCR for CMV, HSV and VZV must be done in specific pa*ents CSF Opening pressure measurement

19 CSF Indices in different dx states Medscape- Cerebrospinal Fluid AnalysisUpdated; Author: Alina G Sofronescu, PhD; Chief Editor: Thomas M Wheeler, MD

20 Ques*on 1 A 39 yr old female is evaluated for 1 week hx of painless blurred vision in the right eye. Her only other visual symptoms has been an increased number of floaters in the right eye for about 3 mths. She has no photophobia, pain with reading, trauma, or recent illness. She has hx of IV drug use but has been clean for 6 yrs. She has no other medical problems and takes no medica*ons. On physical exam T 98.2 F, HR -72, RR 14, BP 126/72 mmhg. There is no conjunc*val injec*on, pupils react to light and accommoda*on. Visual acuity in the right eye is 20/30 and 20/20 in the let eye. Fundoscopy shows fluff yellow re*nal lesions with some associated hemorrhage consistent with CMV re*ni*s.

21 Ques*on 1 Which of the following is the most likely underlying disease? A. Endocardi*s B. Hepa**s C C. HIV infec*on D. Mul*ple sclerosis

22 Empiric therapy for Bacterial Meningi&s Am Fam Physician. 2010;82(12):

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24 Steroids or no Steroids? Reduces morbidity and mortality* Give before or at the same *me as the first dose of an*bio*cs Doses studied Dexamethazone 0.3 mg/kg/day x 7 days *Only shown for pneumococcal and Tuberculous meningi*s meningi*s in adults and Haemophilus meningi*s in children Girgis, Nabil I., et al. "Dexamethasone adjunc*ve treatment for tuberculous meningi*s." The Pediatric infec*ous disease journal 10.3 (1991):

25 Complica&ons and Sequelae Ventriculi*s Empyema Cerebri*s Abscess forma*on Hearing impairments Seizures Cranial Nerve Palsies Hydrocephalus

26 Preven&on Immuniza*on Meningococcal vaccine Meiningococcal Conjugate Vaccine (Menomune) Meningococcal Polysacchride Vaccine (Menactra) Meningococcal b strain vaccine (Trumenba) H. influenza conjugate vaccine Pneumovax 23 vaccine* Prevnar 13 vaccine Chemoprophylaxis Oral Rifampin or Ciprofloxacin

27 Risk Stra&fica&on for Meningococcal Ages 11 to 12 years Booster at age 16 vaccine College students if they have not already been vaccinated Military recruits if they have not already been vaccinated Travelers to endemic areas Muslim Pilgrims to the Hajj

28 Epidemic Meningi&s Belt

29 Case 2 45-year-old female presents to the ED with fever and headaches, a condi*on she has been experiencing for the past two days. Physical exam reveals neck s*ffness concerning for meningi*s. Lumbar puncture is performed and cerbrospinal fluid (CSF) studies are obtained. Opening pressure is noted at 30 cmh2o. CSF analysis reveals: 2,000 WBCs/µL, PMN predominance, no RBCs, glucose 24mg/dL and protein 106mg/dL. Serum glucose is 86mg/dL. Which of the following is the most likely diagnosis? A. HIV encephali*s B. HSV encephali*s C. Early bacterial meningi*s D. West Nile virus encephali*s E. Late bacterial meningi*s

30 Asep*c meningi*s It is a term used to mean non-pyogenic bacterial meningi*s It describes a spinal fluid formula that typically has: A low number of WBC (usu lymphocy*c) A minimally elevated protein A normal glucose It does not always mean viral meningi*s.

31 Causes of asep*c meningi*s/encephali*s syndrome? Infec*ous HSV 1 and 2 Syphilis Listeria (occasionally) Tuberculosis Cryptococcus Leptospirosis Cerebral malaria African *ck typhus Lyme disease Non-Infec*ous Carcinomatous Sarcoidosis Vasculi*s Dural venous sinus thrombosis Migraine Drug Co-trimoxazole IVIG NSAIDS

32 AIDS- associated cryptococcal meningi*s Usually occurs in advanced HIV CD4 < 100 Sub-acute onset: fever, headache S*ff neck is rare Mortality with treatment is about 10 30% Predictors of death Altered Mental status Low CSF WBC count High CSF cryptococcal an*gen *ter (> 1:1024) Bicanic T, Harrison T; Br Med Bull (2004) 72 (1):

33 AIDS- associated cryptococcal meningi*s CSF findings Elevated pressure is the usual (>70%) Rest of CSF findings are oten unimpressive WBC <50 Glucose: normal or slightly low Protein: normal or slightly elevated 25% have normal WBC, glucose and protein CSF cryptococcal an*gen: % sensi*ve

34 Meningi&s? Which of the following are true statements? a. Early viral meningi*s can have a predominance of polys b. Some viral meningi*s can have low CSF glucose c. Listeria meningi*s can have predominance of mononuclear cells rather than polys d. All of the above

35 Tuberculous Meningi*s Onset is usually sub-acute (2-3 weeks) Usually has prodrome with non specific symptoms, fa*gue, malaise, myalgia, and fever Mental status changes more common Neck s*ffness is rare

36 Encephali*s Encephali*s presents as diffuse or focal neuropsychological dysfunc*on. Although it primarily involves the brain, it oten involves the meninges as well (meningoencephali*s) hhp://emedicine.medscape.com/ar*cle/ overview

37 Symptoms Fever, headache, nausea and vomi*ng, lethargy, and myalgias Behavioral and personality changes Decreased level of consciousness Neck pain, s*ffness Photophobia Lethargy Generalized or focal seizure Flaccid paralysis

38 Diagnos*c tes*ng Complete blood count (CBC) Serum electrolytes and glucose levels Urine or serum toxicology screening Lumbar Puncture for CSF HSV cultures of suspicious lesions and a Tzanck smear Viral cultures of CSF, including HSV Blood cultures for bacterial pathogens Heterophile an*body and cold agglu*nin tes*ng for EBV Serologic tests for Toxoplasma

39 Imaging CT MRI EEG

40 Cerebral Abscess Usually spread from con*guous areas, mastoids, sinuses and ears Hematogenous spread from endocardi*s Commoner in older pa*ents, alcoholics and immunosuppressed High mortality up to 80%

41 Summary CNS infec*ons are cause significant morbidity and mortality All cases need quick evalua*on and treatment Management in most cases is empiric based on pa*ent age and risk factors Have a high index of suspicion for raised intracranial pressure

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