Clinical Problem Solving June 22, 2016 Harry Hollander, MD Sam - - PowerPoint PPT Presentation

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Clinical Problem Solving June 22, 2016 Harry Hollander, MD Sam - - PowerPoint PPT Presentation

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6/22/2016 Chief Complaint Altered mental status Clinical Problem Solving June 22, 2016 Harry Hollander, MD Sam Brondfield, MD Thanks to Niraj Shanbhag for case and adapted slides. 2 History of Present Illness HPI continued 74 yo

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SLIDE 1

6/22/2016 1

Clinical Problem Solving

June 22, 2016

Thanks to Niraj Shanbhag for case and adapted slides.

Harry Hollander, MD Sam Brondfield, MD

Chief Complaint

  • Altered mental status

2

History of Present Illness

  • 74 yo Chinese woman presents with AMS.

– In preceding 4 weeks was admitted 3 times to

  • utside hospitals for AMS with intermittent fever

– 1st OSH admission: AMS + fever, discharged on azithromycin for presumed CAP

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HPI continued

  • 74 yo Chinese woman presents with AMS

– 2nd OSH admission: 2 weeks later c/o painless L eye vision loss – Diagnosed with endophthalmitis, treated with intravitreal vancomycin, ceftazidime, voriconazole – Negative vitreal and blood cultures, negative vitreous fluid PCR for HSV, CMV, and toxoplasmosis – Normal TTE – CT chest: LLL cavitary lesion – AFB smear neg x3 – Serum toxoplasma IgM 11.4 IU/mL (ref <7.9) – Treated with pyrimethamine, sulfadiazine, leucovorin, prednisone

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SLIDE 2

6/22/2016 2

Clinical Problem Solving

June 22, 2016

HPI continued

  • 74 yo Chinese woman presents with AMS.

– Called to return to hospital 24 hrs later due to incidental MRI brain finding: multifocal ischemia – TEE unrevealing – Telemetry: paroxysmal a-fib – Warfarin started for presumed cardioembolic strokes – Discharged with TB clinic appointment given history and CT findings, no improvement in vision – Exam documented as blind, word-finding difficulties, oriented to person and place

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HPI continued

  • 74 yo Chinese woman presents with AMS.

– At TB clinic f/u visit 2 days later (now 4 weeks after 1st OSH presentation), she was wheelchair bound and nonverbal, significantly worse than 2 days prior. – Sent to ED.

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Clinical Problem Solving

June 22, 2016

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SLIDE 3

6/22/2016 3

Other History

  • PMH: RA, HTN, GERD, glaucoma (blind OD)
  • Meds: Hydroxychloroquine, PPI, metoprolol, timolol

gtt

  • All: NKDA
  • FH: No FH autoimmune disease
  • SH: No substance use, independent in ADLs/IADLs,

immigrated to U.S. in 2006, traveled to Guangzhou in 2014.

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ED Physical Exam

VS: T 103, HR 111, BP 123/81, sat 93% RA Neuro: Moving all four extremities spontaneously, unable to follow commands or verbalize (GCS 6) Remainder of exam unremarkable except as previously noted. Intubated, admitted to ICU.

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Available Labs

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135 129 13.7 12.6 CSF analysis: 13 RBCs 347 WBCs (57% PMN, 11% mono, 31% lymph, 1% eos) Glucose 30 mg/dL Protein 71 mg/dL

Clinical Problem Solving

June 22, 2016

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SLIDE 4

6/22/2016 4

5 days prior Admission

MRI Brain MRI Brain

Innumerable ring-enhancing and diffusion-restricted supra- and infra-tentorial lesions, most consistent with abscesses as well as severe obstructive hydrocephalus

Clinical Problem Solving

June 22, 2016

Initial Treatment

  • Vancomycin, cefepime, metronidazole, ampicillin

(briefly), pyrimethamine, sulfadiazine, and leucovorin

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SLIDE 5

6/22/2016 5

Reassessment

  • Repeat examination

– Arousable to sternal rub – Not following commands, non-verbal – Pupils fixed bilaterally at 6 mm – +corneals, roving eye movements, withdrawal to pain in all 4 extremities

  • Continued to deteriorate with progressive loss of

motor activity and brainstem reflexes

17 18

Hospital course

  • A diagnostic test was performed…

19

Diagnostic Test:

  • A. Nerve conduction study
  • B. Electroencephalogram
  • C. Full body PET/CT
  • D. Brain biopsy
  • E. Retinal biopsy

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N e r v e c

  • n

d u c t i

  • n

s t u d y E l e c t r

  • e

n c e p h a l

  • g

r a m F u l l b

  • d

y P E T / C T B r a i n b i

  • p

s y R e t i n a l b i

  • p

s y

0% 4% 15% 67% 15%

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SLIDE 6

6/22/2016 6

Brain Biopsy

  • Brain biopsy from hospital day 4 returned

nondiagnostic revealing only mild gliosis and no inflammatory infiltrate or microorganisms.

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Brain Biopsy

Repeat Lumbar Puncture

  • On hospital day 10, repeat LP performed
  • Broad spectrum antibiotics were stopped and

anti-TB and amphotericin B were started.

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LP #1 13 RBC 347 WBC (57 N, 11 M, 31 L, 1 E) Glucose 30 Protein 71 LP #2 1 RBC 123 WBC (50 N, 17 M, 30 L, 3 E) Glucose 61 Protein 136

Brain Biopsy LP #1 LP #2 Abx stopped

Repeat MRI

  • Repeat brain MRI on hospital day 14 showed

increase in number and size of brain lesions and interval development of basilar meningitis.

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Brain Biopsy LP #1 LP #2 Abx stopped Repeat MRI

Clinical Problem Solving

June 22, 2016

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SLIDE 7

6/22/2016 7

Repeat Brain Biopsy

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Brain Biopsy #1 Brain Biopsy #2

Repeat Brain Biopsy

  • Repeat brain biopsy showed severe necrotizing

vasculitis of unclear etiology, with prominent eosinophils, chronic inflammatory cells, and neutrophils but without significant granulomatous component.

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Brain Biopsy LP #1 LP #2 Abx stopped Brain Biopsy #2

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Brain Biopsy Stains

  • PAS and GMS stains neg for fungal organisms
  • Gram stain neg
  • Steiner stain neg for spirochete organisms
  • Immunohistochemistry neg for toxoplasmosis
  • Immunostains for CD20 and CD3 showed a

mixed population of lymphocytes without a neoplastic population

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SLIDE 8

6/22/2016 8

Clinical Problem Solving

June 22, 2016

Diagnosis…

  • A. Bacterial infection
  • B. Fungal infection
  • C. Protozoal infection
  • D. Mycobacterial infection
  • E. Malignancy
  • F. Thromboembolic disease
  • G. Autoimmune vasculitis
  • H. Demyelinating disease

30 B a c t e r i a l i n f e c t i

  • n

F u n g a l i n f e c t i

  • n

P r

  • t
  • z
  • a

l i n f e c t i

  • n

M y c

  • b

a c t e r i a l i n f e c t i

  • n

M a l i g n a n c y T h r

  • m

b

  • e

m b

  • l

i c d i s e a s e A u t

  • i

m m u n e v a s c u l i t i s D e m y e l i n a t i n g d i s e a s e

4% 4% 13% 0% 25% 4% 0% 50%

Hospital course

  • A diagnostic test was performed…

31

Diagnostic Test

  • Serum Balamuthia mandrillaris IgG returned

borderline positive (1:32)

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SLIDE 9

6/22/2016 9

33

Courtesy of Dr. M. Kelly Keating, DVM Centers for Disease Control and Prevention

Clinical Problem Solving

June 22, 2016

Conclusion

  • Worsening cerebral edema was refractory to

management with hyperosmolar therapy and EVD placed during 2nd brain biopsy.

  • Became hemodynamically unstable likely due to

increased intracranial pressure, and required multiple vasopressors.

  • Family opted for comfort care and the patient

expired on day 17 of her hospitalization.

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FINAL DIAGNOSIS Granulomatous amoebic encephalitis due to Balamuthia mandrillaris

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SLIDE 10

6/22/2016 10

Clinical Problem Solving

June 22, 2016

Amoebic Encephalitis

– Primary amoebic meningoencephalitis

  • Naegleria fowleri

– Fresh water, recreational water activities (summer) – Affects immunocompetent and immunocompromised – Rapid progression (mean sx onset to death = 5 days)

– Granulomatous amoebic encephalitis

  • Acanthamoeba

– Soil, beach sand, brackish water, sewage, air, humidifiers – Largely immunocompromised – Weeks to months of worsening HA, fever, visual/neuro sx

  • Balamuthia mandrillaris

– Soil – Immunocompetent or immunocompromised – Symptoms progress over 2-12 weeks

– High mortality! (99% for Naegleria) – Tx: Ampho B, rifampin, fluconazole, miltefosine, azithromycin

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