1. Approach to the Patient with Altered Mental Status…and Fever

2. Infectious diseases of the nervous system

3. Case 1  20 y/o female college student brought in by her roommate  12 hrs of progressive HA, fevers, chills, and emesis x1  Transient cough and sore throat a couple of weeks before, but has otherwise been healthy  Prior migraine, but “ never like this ”  Brought to ER because she became confused

4. Case 1 Exam  VS 40.1 C, 90/60, 120  Gen: tachycardic, diaphoretic and rigors  Skin: no rash  Neuro: lethargic, no coherent speech, not cooperative with exam, moves all 4 extremities, nuchal rigidity, positive Brudzinski and Kernig ’ s signs

5. Case 1 What could this be?

6. Case 1 LP  Head CT – No mass lesions and no signs of herniation.  Opening Pressure - 40 cm H2O  Cell Count - 3500 WBCs, 78% PMNs  Protein - 260 mg/dL  Glucose - < 30

7. Case 1 Work Up  Non-contrast HCT: Get a stat head CT if there are focal findings or concern for raised ICP prior to LP  Lumbar puncture:  When there is a delay in the LP, do NOT delay treatment:  Get blood cx x2 first  Start dexamethasone and broad spectrum Abx (Vanc + cefe +/- ampicillin) +/- acyclovir  LP as soon as possible–keeping in mind that a retrospective study determined that third-generation cephalosporins sterilize CSF of meningococcus (i.e. no growth on culture) in one-third patients within 1 hour and in all patients by 2 hours, and it sterilized CSF of pnemococcus within 4-10 hours.

8. Bacterial Meningitis When do you perform a lumbar puncture? Have a low suspicion! In the Dutch Meningitis Cohort Study, at least 2 of the 4 hallmark symptoms of meningitis (headache, neck stiffness, fever, and altered mental status) were present in 95% of bacterial meningitis patients. Other clinical features include: photophobia, nausea, vomiting, seizures, rash, and focal neurologic deficits

9. Bacterial Meningitis  CSF findings  Increased opening pressure (20-50 cm H2O)  Increased protein (100-500 mg/dL)  Decreased glucose (< 40 % serum glucose)  Marked Pleocytosis (100-10,000 WBCs/uL)  PMN predominant  Positive Gram Stain in ~60% or higher  Positive CSF Cx in ~75%  Blood Cultures  Useful especially if LP is delayed. Get PRIOR to Abx.  Positive in 50-90% of bacterial meningitis

10. Bacterial Meningitis: Empiric Treatment  Adult (community)  Ceftriaxone 2 g IV q 12 hrs, Vancomycin 15 mg/kg q12 (nl GFR)  Elderly (>50)/Immunocompromised/Pregnant/Alcoholic  Ceftriaxone 2 g IV q 12 hrs, Vancomycin (adjust according to GFR), Ampicillin 2 g IV q 4 hrs (adjust according to GFR)  Acyclovir as clinically indicated  Narrow antibiotics after gram stain, culture  Dexamethasone – 10 mg q6h as adjuvant for bacterial meningitis  Start prior to or with the initial dose of antibiotics.

11. Case 2  42 y/o female  Arrives via EMS after “ shaking all over ”  Received Valium 5 mg per EMS  Husband states she has been “ acting crazy and talking to people who aren ’ t there today ”  PMH: HTN

12. Case 2 Exam  T 39.0  No meningismus  Somnolent, but withdraws 4 ext to deep stimulation, and localizes to central stimulation  Work Up  WBC 18.1 (Lymph predominant)  Serum/UDS neg

13. Case 2 Workup  HCT: nl  CSF  Opening Pressure 28  TC 1500; 350 nucs (100% lymphocytes)  Positive xanthochromia  Gram stain: no organisms  Protein 80  Glucose 65

14. Case 2 EEG

15. What could this be?

16. HSV Encephalitis  Accounts for 10-15% of viral encephalitis in the US  Mortality  Untreated: 70%  Treated: 20%  Morbidity  Even with treatment, 25%-33% of survivors required long term supportive care.  50% returned to normal life.

17. HSV Encephalitis: Presentation  In over 90% of cases, HSV presents with the typical triad:  Headache  Fever  Alteration in mental status  Frank psycosis, somnolence, stupor or coma  Seizures: focal or generalized  Visual field defects  Aphasia: when the dominant hemisphere is involved (stroke mimic)  Hemiparesis/hemisensory loss/ataxia

18. HSV Encephalitis  CSF  OP elevated  Lymphocytic pleocytosis (10-1000/uL)  Occasionally NORMAL  +/- RBCs or xanthochromia  Protein - moderate elevation  Glucose NL  HSV PCR  100% specific  ~90-95% sensitive  If high clinical suspicion and initial PCR (-), repeat

19. HSV Encephalitis  EEG  Generalized slowing, PLEDs, or temporal sharp waves  HCT  Normal or subtle edema, +/- blood  MRI  Frontotemporal increased signal on T2/FLAIR. +/- contrast enhancement, +/- blood products

20. HSV Treatment  Acyclovir  10 mg/kg IV Q8 hrs x 14-21 d  Adjust for renal function; ARF and crystal nephropathy are risks of this medication  Decrease risk with maintenance IVF  Monitor renal function