J. Stephen Huff, MD

A case of altered mental statusA case of altered mental status

J. Stephen Huff, MDAssociate Professor

Emergency Medicine and Neurology

University of VirginiaCharlottesville, Virginia

J. Stephen Huff, MD

Let’s talk about a case...Let’s talk about a case...

• 52 year-old man brought to ED by EMS

• CC: Frontal headache +

J. Stephen Huff, MD

History of Present IllnessHistory of Present Illness

• 3 weeks of frontal headache

• Saw primary care physician 1 week ago

• Cranial CT obtained– no intracranial abnormalities

– right maxillary sinusitis

– started on an antibiotic • (amoxicillin / clavulanate)

J. Stephen Huff, MD

J. Stephen Huff, MD

J. Stephen Huff, MD

History of Present IllnessHistory of Present Illness1 day prior to ED visit1 day prior to ED visit

• Headache worsened

• Episodes blurred vision and confusion

• Seen again by primary care physician

• Switched antibiotic to moxifloxacin

J. Stephen Huff, MD

History of Present IllnessHistory of Present IllnessDay of ED visitDay of ED visit

• Awakened 6 AM severe headache

• Falls or syncope or seizures?

• Agitated, confused, hallucinating?

• Arrived ED 0840 by EMS

J. Stephen Huff, MD

Past Medical HistoryPast Medical History

• Psoriasis with vasculitis (digital ischemia)

• Non-insulin dependent diabetes

• Hypertension, coronary artery disease

• Current medications-– Prednisone, celecoxib, metformin, glipizide,

esomeprazole, candesartan, ASA, diltiazem, cyclobenzaprine, fluticasone / salmeterol inhaled

J. Stephen Huff, MD

Social historySocial history(after arrival of family later)(after arrival of family later)

• Works as truck driver

• Married, lives with family

• Past smoker > 40 pack-years

• Alcohol, drug use denied

J. Stephen Huff, MD

Physical examinationPhysical examination

• Restless, agitated

• 147/86, p 96, RR 16, Temp 36.9

• SaO2 99% (room air)

• Will follow simple commands

• Responds with name

• Looking off into space

J. Stephen Huff, MD

Physical examinationPhysical examination

• Difficult

• General examination unremarkable

• Digit amputations left hand

• Psoriatic plaques

• Chest clear; no murmurs

J. Stephen Huff, MD

Patient description...Patient description...

• Restless, agitated• Rolling back and forth• No consistent meaningful responses• Neurologic examination

– moves all extremities...– Pupils 4 mm, equal, reactive

J. Stephen Huff, MD

something not rightsomething not right

• Confusion

• Agitation

• Acute delirium

• Altered mental status

J. Stephen Huff, MD

Differential diagnosisDifferential diagnosisinitialinitial

• Withdrawal syndrome– alcohol

– benzodiazepines

• Intoxication– alcohol

– benzodiazepines

J. Stephen Huff, MD

Differential diagnosisDifferential diagnosis

• Seizures– post-ictal state

– non-convulsive status epilepticus

• CNS infection?

• CNS structural?

• Systemic infection?

• Metabolic disturbance

...may co-exist...

J. Stephen Huff, MD

Initial approachInitial approach

• IV access

• Rapid glucose determination

• Thiamine

• Laboratory and other blood tests

• Sedation for safety?

• More history?

J. Stephen Huff, MD

Sedate the patient?Sedate the patient?What is your choice?What is your choice?

a) midazolam (Versed) 4 mg IV

b) lorazepam (Ativan) 2 mg IV

c) haloperidol (Haldol) 5 mg IV

d) fentanyl mcg IV

e) avoid sedation if at all possible

J. Stephen Huff, MD

ED course....ED course....

• Family arrived-confirmed no history of drug or alcohol abuse pattern

• Family doubted ingestion

• Altered mental status worsening

J. Stephen Huff, MD

Laboratory resultsLaboratory results

• WBC 13,700 platelets 310, 000

• Na 132, bicarb 24. Cr 1.1 BUN 20

• Glucose 207 Lactate 1.6

• Urinalysis unremarkable

• Hepatic functions unremarkable

J. Stephen Huff, MD

Differential diagnosis revisitedDifferential diagnosis revisited

• Withdrawal syndrome• Intoxication• Seizures

– post-ictal state– non-convulsive status epilepticus

• CNS infection?• CNS structural?• Systemic infection?• Metabolic disturbance

J. Stephen Huff, MD

Differential diagnosis revisitedDifferential diagnosis revisited

• Withdrawal syndrome• Intoxication• Seizures

– post-ictal state– non-convulsive status epilepticus

• CNS infection?• CNS structural?• Systemic infection?• Metabolic disturbance

J. Stephen Huff, MD

Clinical EvidenceClinical Evidence

• Afebrile

• White blood cell count indeterminate

• Supple neck

• CT a week ago showed sinusitis

J. Stephen Huff, MD

a few words about Kernig et ala few words about Kernig et al

• Tests for neck rigidity and stiffness....

• What does supple mean, anyway?

J. Stephen Huff, MD

J. Stephen Huff, MD

J. Stephen Huff, MD

Jolt accentuation of headache Jolt accentuation of headache maneuvermaneuver

...bottom line... ...bottom line...

J. Stephen Huff, MD

Pre-test probabilities?Pre-test probabilities?balancing actbalancing act

• Acute bacterial meningitis?

• Other CNS infection?

• CNS structural lesion?– brain abscess?

– parameningeal infection?

J. Stephen Huff, MD

CNS Infection?CNS Infection?What is your choice for next step?What is your choice for next step?

a) empiric antibiotics

b) cranial CT

c) lumbar puncture

d) MRI

e) a, b, and c

J. Stephen Huff, MD

Working planWorking plan

• Presumed CNS infection....

• Concerned possibility of brain abscess....

• Did not want to delay medical therapy

J. Stephen Huff, MD

What medication(s) would you give this patient?What medication(s) would you give this patient?

a) ceftriaxone or other cephalosporin

b) vancomycin

c) acyclovir

d) dexamethasone

e) all of the above

J. Stephen Huff, MD

a) ceftriaxone - why?

b) vancomycin - why?

c) acyclovir - why?

d) dexamethasone - why?

J. Stephen Huff, MD

Empiric therapy for suspected Empiric therapy for suspected bacterial meningitisbacterial meningitis

• Laboratory-guided ?

• Age or risk-factor guided?

J. Stephen Huff, MD

Age-guided therapy for suspected Age-guided therapy for suspected bacterial meningitisbacterial meningitis

• Ceftriaxone* appropriate for all outside of neonatal period (>3 months)

• Vancomycin for possible resistant S. pneumoniae

• Listeria possible at extremes of age– add ampicillin if age less than 1-3

months or greater than 50 years

J. Stephen Huff, MD

Is encephalitis a possibility?Is encephalitis a possibility?Herpes simplex encephalitisHerpes simplex encephalitis

• What are probabilities?

• Is timing as important?

• Should further tests be run? What?

• Empiric acyclovir?

J. Stephen Huff, MD

Steroids?Steroids?

• Are steroids useful or important in acute bacterial meningitis?

• Dexamethasone studies...

J. Stephen Huff, MD

Steroids in acute bacterial meningitisSteroids in acute bacterial meningitis

• Conflicting studies through the years• Most recent - 301 adults with acute bacterial meningitis

– randomized– 10 mg dexamethasone 15-20 minutes before antibiotics– 10 mg every 6 hours for four days

• Reduction of adverse outcomes and death (26% v. 52%)• Greater benefit in most ill patients....

De Gans et al (NEJM 2002; 347:1549)

J. Stephen Huff, MD

What medication(s) would you give this patient?What medication(s) would you give this patient?

a) ceftriaxone or other cephalosporin

b) vancomycin

c) acyclovir

d) dexamethasone

e) all of the above

J. Stephen Huff, MD

CT first?CT first?

• Risk of deterioration after LP in presence of mass lesion?– pre-test probability?

– risk factors?

– adequate exam?

J. Stephen Huff, MD

J. Stephen Huff, MD

J. Stephen Huff, MD

J. Stephen Huff, MD

LPLP

• Lumbar puncture attempted

• Procedural sedation + restraints

• Initial attempts failed.....options?

J. Stephen Huff, MD

LP optionsLP options

• Fluoroscopy?

• Is it important now in this case?

– after all, broad antibiotic coverage...

a) acceptable to defer LP until later time?

b) go forward at all costs to get fluid?

c) defer for moment; revisit later?

J. Stephen Huff, MD

What we did....What we did....

• Ceftriaxone, Vancomycin (0915)

• Acyclovir

• Dexamethasone (1211)

• Invited consultants to be involved

• Sedation for protection and CT

• Procedural sedation and restraints

• With effort obtained clear, colorless CSF

J. Stephen Huff, MD

CSF resultsCSF results

• 117 red blood cells

• protein 119

• glucose 56

• 121 white cells– 22% segmented, 77% lymphocytes

J. Stephen Huff, MD

What type of CNS infection What type of CNS infection does this patient have?does this patient have?

a) bacterial meningitis

b) viral meningitis

c) encephalitis

d) another CNS infection

e) cannot tell with certainty

J. Stephen Huff, MD

Call from laboratory...Call from laboratory...

• Requesting India Ink test

• 3+ encapsulated yeast

J. Stephen Huff, MD

J. Stephen Huff, MD

Fungal meningitis...Fungal meningitis...

• Cryptococcus neoformans most common

• Amphotericin or other therapy?

J. Stephen Huff, MD

Fungal meningitis...Fungal meningitis...

• Induction with amphotericin B

• Longer term therapy with fluconazole

• Liposomal amphotericin

• CSF pressures....

J. Stephen Huff, MD

MRIMRI

• Additional imaging obtained....

• Rule out small masses

• Rule out parameningeal involvement

J. Stephen Huff, MD

J. Stephen Huff, MD

J. Stephen Huff, MD

Case ConclusionCase Conclusion

• Admitted to ICU

• Amphotericin given

• Others discontinued following studies

• Rapid improvement in confusion

• MRI- extensive sinusitis

J. Stephen Huff, MD

Case ConclusionCase Conclusion

• Repeat LP - OP 27-->11 cm H2O

• Home on intravenous amphotericin

• (then to fluconazole)

• Persistent headaches

J. Stephen Huff, MD

Case ConclusionCase Conclusion

• Headaches thought to be from ICP

• Improved following VP shunt

J. Stephen Huff, MD

Cryptococcus neoformansCryptococcus neoformans

• 1/100,000 in non-HIV infected population

• Chronic, sub-acute, or acute

• Encapsulated yeast

• Steroid use

J. Stephen Huff, MD

J. Stephen Huff, MD

J. Stephen Huff, MD

Final thoughtsFinal thoughts

• Empiric therapy just that, empiric

• Transition to definitive therapy

• Unusual presentation of unusual diseases...

• Correct diagnosis needed for correct therapy

J. Stephen Huff, MD

Final thoughtsFinal thoughts

• Think treatable causes

• Do not delay therapies of treatable causes for diagnostic tests....

• Empiric therapy for bacterial meningitis

• Dexamethasone

J. Stephen Huff, MD

Questions?Questions?

J. Stephen Huff, MD

jshuff@virginia.edu

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