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 Chinese woman presents with AMS • 74 yo Chinese woman presents with AMS. – 2 nd OSH admission: 2 weeks later c/o painless L eye – In preceding 4 weeks was admitted 3 times to vision loss outside hospitals for AMS with intermittent fever – Diagnosed with endophthalmitis, treated with intravitreal – 1 st OSH admission: AMS + fever, discharged on vancomycin, ceftazidime, voriconazole azithromycin for presumed CAP – 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 3 4 1
6/22/2016 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 Clinical Problem – Telemetry: paroxysmal a-fib Solving – Warfarin started for presumed cardioembolic strokes – Discharged with TB clinic appointment given June 22, 2016 history and CT findings, no improvement in vision – Exam documented as blind, word-finding difficulties, oriented to person and place 6 HPI continued • 74 yo Chinese woman presents with AMS. – At TB clinic f/u visit 2 days later (now 4 weeks after 1 st OSH presentation), she was wheelchair bound and nonverbal, significantly worse than 2 Clinical Problem days prior. Solving – Sent to ED. June 22, 2016 7 2
6/22/2016 Other History ED Physical Exam • PMH: RA, HTN, GERD, glaucoma (blind OD) VS: T 103, HR 111, BP 123/81, sat 93% RA • Meds: Hydroxychloroquine, PPI, metoprolol, timolol Neuro: Moving all four extremities spontaneously, gtt unable to follow commands or verbalize (GCS 6) • All: NKDA Remainder of exam unremarkable except as previously noted. • FH: No FH autoimmune disease • SH: No substance use, independent in ADLs/IADLs, immigrated to U.S. in 2006, traveled to Guangzhou in Intubated, admitted to ICU. 2014. 9 10 Available Labs 129 13.7 135 12.6 Clinical Problem Solving CSF analysis: 13 RBCs 347 WBCs (57% PMN, 11% mono, 31% lymph, 1% eos) June 22, 2016 Glucose 30 mg/dL Protein 71 mg/dL 11 3
6/22/2016 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 5 days prior Admission Initial Treatment • Vancomycin, cefepime, metronidazole, ampicillin (briefly), pyrimethamine, sulfadiazine, and leucovorin Clinical Problem Solving June 22, 2016 16 4
6/22/2016 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 Diagnostic Test: A. Nerve conduction study • A diagnostic test was performed… B. Electroencephalogram 67% C. Full body PET/CT D. Brain biopsy E. Retinal biopsy 15% 15% 4% 0% m T y y y s d C s a / p p u r T o o t g E i s b i b o P l n a n l o y a h d a i n i t p o r i c B t e b e u c d R n l l n u e o o F c r t e c v e r e E l N 19 20 5
6/22/2016 Brain Biopsy Repeat Lumbar Puncture • Brain biopsy from hospital day 4 returned • On hospital day 10, repeat LP performed nondiagnostic revealing only mild gliosis and LP #1 LP #2 no inflammatory infiltrate or microorganisms. 13 RBC 1 RBC 347 WBC (57 N, 11 M, 31 L, 1 E) 123 WBC (50 N, 17 M, 30 L, 3 E) Glucose 30 Glucose 61 Protein 71 Protein 136 • Broad spectrum antibiotics were stopped and anti-TB and amphotericin B were started. Brain Biopsy LP #2 Brain Biopsy LP #1 Abx stopped 21 22 Repeat MRI • Repeat brain MRI on hospital day 14 showed increase in number and size of brain lesions and interval development of basilar meningitis. Clinical Problem Solving June 22, 2016 Brain Biopsy LP #1 Repeat MRI LP #2 Abx stopped 23 6
6/22/2016 Repeat Brain Biopsy Repeat Brain Biopsy • Repeat brain biopsy showed severe necrotizing Brain Biopsy #1 Brain Biopsy #2 vasculitis of unclear etiology, with prominent eosinophils, chronic inflammatory cells, and neutrophils but without significant granulomatous component. LP #1 Brain Biopsy LP #2 Brain Biopsy #2 Abx stopped 26 25 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 27 28 7
6/22/2016 Diagnosis… A. Bacterial infection B. Fungal infection 50% C. Protozoal infection D. Mycobacterial infection Clinical Problem E. Malignancy Solving F. Thromboembolic disease 25% G. Autoimmune vasculitis 13% H. Demyelinating disease June 22, 2016 4% 4% 4% 0% 0% y n n n n c e s e o o o o n s t i s i i i a i a t t i t t a e l e c c c c n s u s e e e e g i c i f f f f i d s d n n n n l a i i i i a c v g l l l l M i n a a a a o l e i g o i n t i r n r b u a e z e m n t u o t m c F t c e l i a o a o m e B r b b y P o i m m o c t e y o u D M r A h T 30 Hospital course Diagnostic Test • Serum Balamuthia mandrillaris IgG returned borderline positive (1:32) • A diagnostic test was performed… 31 32 8
6/22/2016 Clinical Problem Solving June 22, 2016 Courtesy of Dr. M. Kelly Keating, DVM Centers for Disease Control and Prevention 33 Conclusion FINAL DIAGNOSIS • Worsening cerebral edema was refractory to Granulomatous amoebic encephalitis management with hyperosmolar therapy and due to Balamuthia mandrillaris EVD placed during 2 nd 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. 35 36 9
6/22/2016 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) Clinical Problem – Granulomatous amoebic encephalitis • Acanthamoeba Solving – Soil, beach sand, brackish water, sewage, air, humidifiers – Largely immunocompromised – Weeks to months of worsening HA, fever, visual/neuro sx • Balamuthia mandrillaris June 22, 2016 – Soil – Immunocompetent or immunocompromised – Symptoms progress over 2-12 weeks – High mortality! (99% for Naegleria ) – Tx: Ampho B, rifampin, fluconazole, miltefosine, azithromycin 38 10
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