Clinical Case Conference February 27, 2006

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Clinical Case ConferenceFebruary 27, 2006

• Robin Trotman, D.O.

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DisclosuresSection of Infectious Diseases

• Kevin High, M.D.
• Grant/Research Support Cubist Pharmaceuticals,
  Astellas Pharma US, Inc.
• Consultant Merck Co., Inc.
• Speakers Bureau Pfizer Pharmaceuticals
• James Peacock, M.D.
• Ownership in Common Stock Pfizer
  Pharmaceuticals
• Sam Pegram, M.D.
• Grant/Research Support Roche, Bristol-Myers
  Squibb, Gilead, Schering-Plough, Tibotec
  Pharmaceuticals
• Consultant Abbott Laboratories,
  GlaxoSmithKline, Boehringer Ingelheim, Gilead,
  Roche
• Speakers Bureau Abbott Laboratories,
  GlaxoSmithKline, Boehringer Ingelheim, Merck,
  Pfizer Pharmaceuticals

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DisclosuresSection of Infectious Diseases

• Aimee Wilkin, M.D.
• Grant/Research Support Abbott Laboratories,
  GlaxoSmithKline, Tibotec Pharmaceuticals,
  Bristol-Myers Squibb Company, Gilead
• Christopher Ohl, M.D.
• Grant/Research Support Cubist Pharmaceuticals,
  Gene-Ohm Sciences, Merck Pharmaceuticals
• Speakers Bureau/Consultant Ortho-McNeil
  Pharmaceuticals, Cubist Pharmaceuticals,
  Sanofi-Aventis Pharmaceuticals, Pfizer
  Pharmaceuticals, Bayer Pharmaceuticals

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DisclosuresSection of Infectious Diseases

• Tobi Karchmer, M.D.
• Grant/Research Support Gene-Ohm Sciences
• Speakers Bureau Pfizer Pharmaceuticals, Cubist
  Pharmaceuticals, Cepheid,
• Gene-Ohm Sciences
• Consultant C.R. Bard
• Robin Trotman, D.O.
• Speakers Bureau Pfizer Pharmaceuticals

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Case 1-Cont. from last CCC

• 71yo wm with ICM, CKD, PVD, COPD, and other
  comorbidities was admitted to FMC 11/11/05 for
  dyspnea and edema.
• Initial complaints were c/w decompensated CHF.
• He also described a fall 10 weeks ago and left
  elbow swelling.

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Case 1

• At an outside clinic he underwent aspiration of
  his Olecranon bursa and was given a script for
  prednisone.
• He was admitted several days later via the ED
  with c/o dyspnea, increased abdominal girth, left
  elbow pain, and back pain.

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Case 1

• Admitted for diuresis and pain control.
• T12 compression frx. was seen on plain film.
• On further questioning on HD2, he described
  intermittent fevers.
• Of note, right IJ Hickman catheter was placed
  5/23/05. He had no complaints regarding the
  catheter.

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Case 1

• ROS As above, otherwise negative. He denied any
  redness or drainage from his left elbow.
• PMH Need an entire slide for this!!!
• Again, Resiliency!!!!

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Case 1

• RAS-s/p renal a. stent in 1985 with
  intraoperative cardiac arrest
• PVD-s/p R axillo-bifemoral graft, with subsequent
  thrombosis in 2001 and R to L femoral graft.
  Multiple subsequent thromboses.
• COPD- FEV1
• DM2
• CAD-s/p CABG 11/2002 with PTCI X2
• GI hemorrhage
• BiV PM/AICD placed in 4/2004
• Hickman catheter place 5/05 for Natrecor
  infusions
• TIA with 95 L ICA and 75 R ICA stenosis
• On 9/30/05 he was admitted for GI hemorrhage,
  vasc surg recommended leaving the HC in place.

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Case 1

• MEDS Vancomycin, etc.., etc..,
• ALL Only antibiotics are included here PCN,
  doxycycline, tetracycline, erythromycin,
  macrodantin, sulfa, prednisone?, antihistamine,
  and many more!!
• SOC HX previous smoker, no pets, lives in WS
  with his wife, disabled

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Case 1

• P/E Initially, T 98, 154/71 _at_ 86, 20, SpO2 88
  on 2L NC.
• Chronically ill appearing, appears dyspneic
• Decreased BS in b/l bases with rales, JVD, edema.
• Ascites
• Fluid _at_ L olecranon bursa without erythema or
  induration. Point tenderness at T spine.
• Otherwise, nonfocal exam.
• Very pleasant, spunky, ready to go home. Today!!!

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Case 1

• Initial labs
• WBC 12.6, 80 PMN, Hgb 10, PLTs 328K
• BUN/Cr 52/2.9, BNP 2,5000
• CXR showed signs of CHF

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Case 1 Hospital course

• On HD2, temp 100.3 and BCX from admit were
  resulted as 2/2 with MSCoNS and third BCX
  obtained was also positive.
• Vanco started, vasc surg consult with the
  impressions that the pos. BCX were false BCX.
  Leave Hickman Cath in and consult ID.
• ID consult 11/14-cath needs to come out and
  repeat BCX, rx vanco, echo

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Case 1 Hospital course

• CoNS was susceptible to erythro, clinda,
  cefazolin, gent, naf, PCN, rif, tetracycline,
  vanco2.0, and res to TMP/SMX.
• 11/21 TEE

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Case 1 Hospital course

• Echo findings
• Moderate size cyst like structure attached by a
  stalk to the TV. The coronary sinus wire has
  solid lesion with central lucency c/w a
  vegetation.
• Too large to remove percutaneously.

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Case 1 Hospital course

• Would need thoracotomy to remove wires.
• 11/22 Hickman removed and f/u Bcx negative. PICC
  placed.
• 11/22 BUN/Cr 79/2.4
• Current Mgt was vancomycin, retention of PM/AICD,
  and d/c to home.
• New ID consultant on service the weekend of Nov.
  11/26

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Case 1 Questions

• What do you think that the new ID consultant
  said?
• Medical mgt. of MSCoNS IE with retained AICD?
  Can the lead be safely removed percutaneously?
  And does it matter what the ID doc thinks about
  this question?
• What do you tell the patient, his family, and the
  PCP for his chance of cure?
• Abx. and duration recs.? v
• Any need to use vancomycin instead of nafcillin? v

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Case 1 Hospital course

• Any credence to the concept of heterogenous
  populations of MSCoNS and the emergence of
  resistance? Small Colony Variants? v
• My rationale was that the infection will not be
  cured with med. mgt. alone, if he fails due to
  the emergence of resistance, then switch. In the
  meantime, give him the best opportunity at cure
  with the most cidal drug.

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PM I.E. with MS CoNS

• 1. Microbiology of CoNS resistance v
• 2. Concept of heterogenous populations of CoNS
  and emergence of methicillin resistance. Small
  Colony Variants? v
• 3. Pacemaker/AICD I.E. and medical mgt. alone.
  Brief review of the numbers-percent chance of
  cure with med. mgt. vs surgical vs perc. removal
  (how big of a veggie can be removed
  percutaneously?)
• Does everyone know how a BiV PM/AICD in placed?

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PM/AICD I.E. with MSCoNSHeterogeneous
population.

• Summary
• If CoNS Ox MICMR phenotype.
• May be able to be transformed in vivo, but
  inherent resistance genes are not present.
• No clinical failures in humans with beta-lactam
  treatment of MSCoNS due to emergence of meth
  resistance.

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PM/AICD I.E. with MSCoNSPM I.E.-Objectives

• 1. Background
• 2. Methods of PM/AICD removal
• 3. Data and prognosis on treatment options for
  PM/AICD I.E.
• 4. Provide this patient a prognosis. (To afford
  the patient an informed decision whether to
  undergo thoracotomy or med mgt. Alone)

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PM/AICD I.E. with MSCoNSPM I.E. Background

• Infection of the device pouch and wire occurs at
  1-7 (0.5-12)
• Infectious Disease Clinics. June 200216477-505.
• PM and AICD (Cardiac Devices CDs) Transvenous
  only.
• TEE required to evaluate the entire system (SVC
  to RV). Increase in sensitivity from 25 to 95,
  except in TV IE.
• BCX are in 80 of CD I.E. and cx of the wires
  reveals the causative agent.

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PM/AICD I.E. with MSCoNSPM I.E. Background

• CD IE occurs in 3 scenarios with equal frequency
  50 of cases of IE in PM recipients involved a
  valve regardless of lead involvement. (CID
  20043968-74)
• 1. IE exclusively on leads
• 2. Combo of lead and valve IE
• 3. Isolated valve inf. independent of leads
• Incidence 400 cases of IE per million CD
  recipients. (.04)(French CID 20043968-74)
  Midway between native valve and prosthetic valve
  IE incidence in the general population.

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PM/AICD I.E. with MSCoNSPM I.E. Background

• Early implantation. Infectious Disease Clinics NA. June
  200216477-505.
• LateCoNS (1-12mo late, 12mo delayed)-25,
  33, 48 of cases
• Both early and late infections are from local
  contamination during implantation.
• Hematogenous seeding of CD conducting system
  during the course of bacteremia is
  rare-neoendothelium and fibrous coating. Chest
  20031241451-9, IDCNA 200216477.
• Exception is S aureus. 29 chance of CD infxn
  following S aureus BSI _at_ 1 yr. Circulation
  20011041029-33.

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PM/AICD I.E. with MSCoNSAHA Scientific
Statement Circulation. 20031082015-2031

• Recent review of the literature and evidence
  based expert opinion
• Great bibliography
• From where many of the stats were taken

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PM/AICD I.E. with MSCoNSChest 20031241451-9

• 31 cases of PM IE. 4,228 devices implanted.
• Prospectively identified all cases of CD
  infection over 10 years.
• 0.6 incidence of IE on CDs. C/w other series
• 7/31 patients with medical mgt alone. All
  relapsed and one died. 1.6 relapses per pt.
  before surgery
• 24 underwent surgical removal (5 sternotomy/19
  perc) 1 relapse, 3 died after surgery, 20 were
  cured at 389 months.
• Only prognostic factor for treatment was absence
  of surgery (P

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PM/AICD I.E. with MSCoNSAnn Int Med
2000133604-8

• 123 CD infections and 117 underwent complete
  device removal with only one relapse (varying
  methods of abx therapy)
• Of the 6 with incomplete removal, 3 had relapse.

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PM/AICD I.E. with MSCoNSAm J Cardiol
199882480-4

• 190 pts with PM IE
• Med Mgt alone-41 mortality rate
• Removal of entire apparatus-19 Mor Rate.
• All cause MR. ie. MR associated with thoracotomy
  was also included.

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PM/AICD I.E. with MSCoNSPercutaneous Removal

• Percutaneous removal has been performed on leads
  with veggies up to 23mm and 100 months following
  implantation. Chest 20031241451-9.
• Within 12 mos, perc. traction can be done.
• Chest 20031241451-9.
• Data showing that wires not amenable to traction
  are often able to be removed with laser sheath.
  Inf Disc Clin NA 200216477.

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PM/AICD I.E. with MSCoNSPercutaneous Removal

• Leads with vegetations 10mm can be safely
  removed without PE complications. Circulation
  1997952095-2107.
• Transvenous removal of leads with vegetations
  from 10-38mm. Am Heart J 2003146339-44
• Dilator sheaths, transfemoral snares, retrieval
  baskets, needles eye snare, laser assisted
  All with some rate of major complication.
• Loosely coined Less-invasive surgical approach
  to percutaneous lead removal. Chang el al. Ann
  Thorac Surg 2005791250-4. True Cowboy surgery!!

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PM/AICD I.E. with MSCoNSPercutaneous
Removal-Complications

• PE may occur following lead extraction in the
  presence of infected vegetations, but their
  sequelae have not been severe, and mortality does
  not change.
• AICD leads are harder to remove
• However, vegetations seem to remain adherent to
  the endocardial surface of the heart after
  removal.
• Perc. removal even with large veggies is the
  goal, unless the PE would be catastrophic
• Complication rate2-2.5, major0.5 no data on
  coronary sinus lead extraction-BUT seem easier to
  dc.
• Current opinions in cardiology 20041919-22

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PM/AICD I.E. with MSCoNSAnn Int Med
2000133604-8

• Successful Medical Mgt See Karchmers chapter in
  Infectious Disease Clinics of North America. June
  200216477-505.
• Anecdotes
• Extensive ID with local instillation of abx
• Indefinite systemic abx.

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PM/AICD I.E. with MSCoNS

• Difficulty of medical mgt is the fibrous matrix
  of dense layers of endotheliazed fibrous tissue
  surrounding the generator and leads.
• Gene ica encodes polysaccharide intercellular
  adhesin responsible for cellular aggregation.
• Poor antibiotic penetration.
• Proven higher mortality.

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PM/AICD I.E. MGT Summary

• Complete explantation-percutaneously at expert
  center, modified perc. approach in China, open if
  needed (rarely).
• Size of veggie and length of time
  post-implantation are relative contraindications
  and not well defined.
• Partial removal (only if infection is clearly
  limited to the removed component)
• Optimize/prolong abx. regimen if medical mgt. is
  the only course.
• Would advise this pt. that cure is not possible.
  Success rate including some prolonged duration of
  suppressive therapy would be between 0-30
  without surgery

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PM/AICD I.E. MGT Summary

• Questions?
• On to next case.

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Case 2

• 69yo WM with htn, djd, and dysrhythmia (s/p PM
  2000) admitted 1/27/06 for difficulty with
  language
• Described as having a stroke in 12/2005 with
  worsening of symptoms

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Time Line

• 12/11/05-Wife noticed first symptom of memory
  loss-words to church songs
• 12/13/05-Developed expressive aphasia and
  difficulty with ADLs, ie. computer
• 12/19-Sx culminated and now with diff. with word
  finding-Taken to ED

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Time Line

• In Forsyth EDc/o dyspnea and bifrontal HA and
  wife described not himself, fogets simple
  tasks, penmanship is different, not able to find
  words and pt. Becomes tearful with frustration
• With hesitance he is oriented X4, neuro exam
  grossly nml, old OD ptosis, otherwise
  unremarkable PE.
• Head CT nml, basic labs nml
• Dx with Word finding difficulty, possible
  localized to left temporofrontal region-ischemic
  vs. partial complex seizure. Admit to stroke
  pathway

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Time Line

• 12/19 Admit Continued nml carotid duplex, nml
  EEG, nml CTA, minimal improvement in sx and d/cd
  with plan for outpt therapy and further w/u.
• 12/25 Barely able to drive
• 1/1/06 Not able to walk
• 1/14 Cortical and functional status decreased?
• 1/18 Returns to neurologist, affect has changed,
  declining speech therapy.
• 1/20 PETDiffuse relative decreased activity
  throughout left cerebral hemisphere, dec.
  activity in the rt cerebellar hemisphere.
  Suggestive of decreased blood flow ie. Carotid
  stenosis, rather than stroke. Cerebellar
  findings suggest cerebellar diaschisis.

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Time Line

• 1/27 Admitted for Angiogram that was normal and
  LP which required IR the following weekday.
• 1/30 LPW1, R237, P96, G123, OP nml
• 2/1 Stable per PT and sent to inpatient rehab
• 2/2 seizure
• 2/3 seizure and sent to IMC under Neurology
• 2/3 EEG with random and irregular 6 cycle theta
  from all electrodes at left hemisphere.
  Generalized encephalopathic and left sharp form
  phase reversal complex.
• 2/3 LPW3, R1000, P127, G80
• Encephalopathy worsens

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Time Line

• 2/11 New ID consultant
• 2/12 Dev. resp.distress requiring ET intubation
• 2/12 Extubated and moved to palliative care.

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Case 2-ROS

• Previous occ. he had transient monocular
  blindness and past hx of syncope, but no symptoms
  at time of first admit.
• Denied ever having meningitis
• Other than new bi-frontal HA described on 12/19,
  his ROS was negative.

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Case 2-PMH

• s/p CVA 12/2005?
• s/p b/l TKA 1994 and R THA 2004
• s/p PM 2000 for syncope-Afib?
• Hx of transient 7th nerve palsy
• s/p L2-L5 hemilaminectomy 12/2000
• Hx of Ank Spon.
• OSA on CPAP

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Case 2-PMH

• 1998 Transient monocular blindness
• 1998 Transient 7th nerve pasly
• 2000 Syncope with PM for a-fib
• 2000 LP done, why?-W3, R1425, P285, no diff
• 2001 LP- Not sure why- Ank Spon?-W-103 84
  segs, R-0, P-378, G-?

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Case 2-Soc Hx

• Retired software engineer, married, occ. Cigar
  smoker, no EtOH, no drugs
• Deer hunter in the N.E. US-Penn in Oct
• Pheasant hunting in SD 12/2005- was not the same
  then
• No other travel, no pets at home.
• Son is ED doc, no fam hx of CNS diseases
• Musician who plays a goat hide bongo drum
  purchased in Haiti.

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Case 2-MEDS PE

• MEDS at the time of admit to neurorehab
• Phenytoin, Lexapro, Altace, enoxaparin, ASA
• P/E Afebrile during the entire hosp course
• On 12/19 his neuro exam was nml other than long
  term memory lapse and writing difficulty.
  Specifically his motor was 5/5 bl ue and le, nml
  tone, decreased vib sensory at ankles only, nml
  cerebellar exam, nml gait

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Case 2-LABS

• CMP WNL
• CBC WBC8.2-S63,L23, M8, E4, B2, otherwise nml
• ESR 2

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FDG PET scan
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Case 2-Sumary?

• Rapidly progressive neurological decline in a 69M
  without clear etiology at this time.
• Vascular causes seemingly ruled out, MRI not
  feasible, EEG and PET grossly abnormal.
• Anyone care to offer up a DDX?
• Any further studies?

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Case 2-Sumary?

• Further studies
• CSF micro all final negative
• IPPD NR
• HSV PCR negative X 2
• EEG with sharpened discharges with a tendency to
  phase reverse over the mid left hemisphere.
• Repeat LP on 2/3 Prot 127 3WBC, 1000RBC
• Meningoencephalitis and WNV serologies neg.

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Case 2-Sumary?

• CSF sent for 14-3-3 protein repeatedly positive
• New thoughts?
• Is the diagnosis nailed down?

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Case 2-Creutzfield-Jakob disease

• 1. Prion disease intro
• -History
• -Types
• -Diseases and definitions
• -Epi
• -Microbiology and pathophysiology
• 2. CJD clinical characteristics
• 3. CJD Diagnosis-MRI, EEG, PET, CSF, BX
• 4. Infection Control Measures

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Case 2-Creutzfield-Jakob diseaseHistory

• 250 y.a. Scrapie was described in sheep and
  goats.
• 1920 H.G. Creutzfeldt described what is now sCJD
• 1921 Jacob also described the same disease with
  pathologic diagnoses
• 1957 Gajdusek described Kuru-Nobel Prize 1976
• 1960s sCJD was described as a slow virus and Kuru
  was described as a similar syndrome but was
  clustered. Hadlow described Kuru and Scrapie
  similarities in histopath severe neuronal
  degeneration and intense reactive astrogliosis
  without inflammation

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Case 2-Creutzfield-Jakob diseaseHistory

• 1966 Alper, Haig, Clarke hypothesized that the
  unit of TSE was an aberrantly folded variant of
  host protein.
• 1967 Griffin suggested that the agent of BSE in
  Europe, Scrapie in Europe, and KURU may be a
  protein as it was resistant to UV rad and
  nucleases.
• Gerstmann-Straussler-Scheinker ds.(GSS), fatal
  familial insomnia, and fCJD were shown to be
  clinically and pathologically similar to sCJD,
  but demonstrated auto-dom.

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Case 2-Creutzfield-Jakob diseaseHistory

• 1982 Prusiner isolated a protease resistant
  glycoprotein and designated it prion
  protein(PrP). Major constituent of infected
  fractions from homogenized brains-- LACK NUCLEIC
  ACID PrionProteinaceous infectious
  particle-Nobel Prize in 1997.
• 1985 BSE discovered and later up to 2 million
  cattle were infected in the UK.
• 1995 First case of vCJD reported, described in
  Brittish adolescents in 1996.
• Recent discovery of Saccharomyces prions

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Case 2-Creutzfield-Jakob diseasePreface

• Research on the fatal TSEs has opened a new
  field of biology over the past 25 years, one that
  is both fascinating and confusing, even to the
  most noted prion researchers.
• Pediatr Infect Dis J 200524371-2.

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Case 2-Creutzfield-Jakob diseaseHuman Diseases

• Creutzfeldt-Jakob disease (CJD)
• -iCJD, sCJD, fCJD
• Fatal Familial Insomnia (FFI)
• Gerstmann-Sträussler-Scheinker (GSS) syndrome
• Kuru
• Variant CJD (nvCJD or vCJD)

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Case 2-Creutzfield-Jakob diseasePrion Intro

• Definitions Vary according to author.
• PrP wild type expressed by host cells and in
  normally folded statePrPsen, PrPc
• PrP in the disease associated isoformPrPSc,
  PrPres. PrPTSE
• The basic concept is that prions are normal host
  proteins that undergo transitions to cause
  neurodegenerative diseases.
• The aa sequences of PrPc and PrPTSE are the
  same, but secondary tertiary structures are
  different. Does not apply to fCJD and GSS.

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Case 2-Creutzfield-Jakob diseasePrion Intro

• All prion diseases show aberrant metabolism of
  the PrPc.
• This is a highly conserved cell surface protein
  and is highly expressed in neurons (but not
  solely).
• Does not jump species. Possibly sheep Scrapie to
  cattle BSE.

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Case 2-Creutzfield-Jakob diseasePathophys
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Case 2-Creutzfield-Jakob diseasePathophys
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Case 2-Creutzfield-Jakob diseasePathophys

• Kuru and vCJD
• Nml host produces nml PrPsen
• Infection-like acquisition of abnormally folded
  protein (PrPres) from external source.
• This induces PrPsen to fold aberrantly into
  PrPres.
• This is then self propogating

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Case 2-Creutzfield-Jakob diseasePathophys

• fCJD and GSS disease
• fCJD-Chromosome mutation results in abnormally
  folded proteinase K-resistant PrPPrPres.
• GSS-Genetic mutation in position 102 of PrP
  results into single aa switch and altered protein
  folding.
• Many other loci have been identified and
  implicated in the multiple diseases.

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Case 2-Creutzfield-Jakob diseasePathophys

• Sporadic CJD
• Most CJD is sporadic and not truly an ID.
• Familial form is Auto Dom with variable
  penetrance
• Fam Hx of CJDOR of 19 (Mandell 6th ed.)
• Mouse model genetics exist for sCJD

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Species jumping rare
71
Women and children eat brains of deceased patients
250 cases
Almost 300 cases
Exception to the species jumping rule
Exception to the species jumping rule

• GSS is longer duration and slower progression
• FFI is progressive untreatable insomnia,
  dysautonomia, thalamic degeneration
• Iatrogenic
• Intracerebral or optic innoculation will behave
  like classic the CJD
• Peripheral innoculation ie. pituitary growth
  hormone may present like Kuru with progressive
  ataxia, mood and personality changes

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Case 2-Creutzfield-Jakob diseaseClinical

• sCJD mcc of prion ds in humans
• sCJD accounts for 90 of CJD
• 1/1,000,000 persons/year
• Rapidly progressive dementia with mean age of 60
  and death in 4-5 months.
• Dementia followed by myoclonus, cerebellar
  ataxia, akinetic mutism, cortical blindness, and
  extrapyramidal features.

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Case 2-Creutzfield-Jakob diseaseDiagnosis-EEG

• Classic EEG pattern is slow background with
  characteristic 1-2Hz sharp wave discharges.
• Sensitivity 65-70
• Key word is PSWCs-Periodic Sharp Wave Complexes

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Case 2-Creutzfield-Jakob diseaseCSF Findings

• CJD CSF Acellular, nml glucose, nml or slightly
  elevated protein.
• Pleocytosis or hypoglycorrhachia favor another
  diagnosis
• 14-3-3 protein, S100, enolase, tau protein nml
  eukaryotic proteins found in CSF of about any CNS
  disease.

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Case 2-Creutzfield-Jakob diseaseCSF Findings

• 14-3-3 is found in the cytoplasm in large
  quantities in cerebral tissue - involved in
  cellular functions like apoptosis
• Therefore, the presence of this protein the CSF
  probably reflect cell destruction, from any
  cause.
• 14-3-3 is the only one of these proteins with
  sufficient enough diagnostic accuracy to make the
  WHO criteria for probable cases of sCJD
• Serial CSF exams will enhance specificity,
  because a false positive from eg. HSV will turn
  negative over time.
• 10 false positive if done in all pts with
  rapidly progressive dementia. Neurology
  200361354

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Case 2-Creutzfield-Jakob diseaseCSF Findings
14-3-3 protein

• Natl. Prion Disease Pathology Surveillance Center
• www.cjdsurveillance.com
• Quantitative better than qualitative
• Sensitivity of 14-3-3 based on cutoff. 8 has
  been reported to be nearly 100 vs 4 with approx
  50 sensitivity
• However, the tests sensitivity is subtype
  specific.
• MM1 and MV1-most common subtypes. Here
  sensitivity approximates 100
• In the non-classical subtypes ie MV2, sensitivity
  is down to 77

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Case 2-Creutzfield-Jakob diseaseCSF Findings
14-3-3 protein

• 14-3-3 Appears to be a very sensitive test for
  the most classic forms of sporadic CJD
• However, the atypical forms (MV2) demonstrate
  basal ganglia hyperintensity
• Take Home DWI MRI with attn. to BG read by
  experienced neuroradiologist and nml 14-3-3 can
  r/o sCJD.
• Neurology 200463410-11 Editorial reviewing the
  most recent data.

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Case 2-Creutzfield-Jakob diseaseDiagnosis-MRI
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Case 2-Creutzfield-Jakob diseaseDiagnosis MRI

• MRI protocol should be T2 and proton density
  axial images at 3-mm cuts and DWI and fluid
  attenuated inversion recovery images (FLAIR).
• Most common findings are increased T2 signals in
  the striatum
• Increased signal in the BG has 70 sens and 90
  specificity for sCJD.
• Abnormalities increase in size and inteisity over
  time
• PET may be helpful but lacks validated data
  supporting its use.

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Case 2-Creutzfield-Jakob diseaseDiagnosis
Putting it all together

• Combined yield of characteristic MRI, EEG,
  Clinical, and CSF findings Can r/o sCJD, can
  also serially re-evaluate and be fairly certain
  of the diagnosis if all the findings are present.
• Neurology Assoc Diagnostic guidelines for
  Probable/Likely

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Case 2-Creutzfield-Jakob disease

• The only way to make definitive diagnosis is by
  histopath.

Neuronal loss and gliosis, spongiform changes,
amyloid plaques, and positive Immunoblot for
PrPTSE.
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Case 2-Creutzfield-Jakob diseaseInfection
Control Issues

• No reported cases of transmission from pleural
  fluid, sputum, tears, semen, milk, blood
  transfusion (Mandell 6th ed.).
• Person to person transmission not reported
• Little evidence that oral ingestion is involved
  in sCJD.

84
Case 2-Creutzfield-Jakob diseaseInfection
Control Issues

• American Neurologic Assoc.
• WHO Inf Cont Guidelines for TSEs www.who.int ,
• CID 2001321348-56

85
Case 2-Creutzfield-Jakob diseaseInfection
Control Issues

• Rutala WA, Weber DJ. CID 200439702-9.
• Disinfection and Sterilization in Health Care
  facilities What Clinicians Should Know.
• Only critical devices and semicritical devices
  contaminated with high-risk material like brain
  or eye tissue require prion processing.
• Combo of NaOH 1N for 1h, remove and rinse in H2O,
  autoclave _at_ 132 C, not more than 134 C.
• Discard objects that will be rendered unusable
• Clean surfaces with 110 dilution of
  Hypochlorite soln.
• Guanidine thiocyanate _at_ 4M

86
Case 2-Creutzfield-Jakob diseaseTreatment

• Universally fatal
• Quinacrinine sCJD-slowed progression transiently
• Congo OrangeAnion-Delay ds in rodents
• Doxycycline In vitro Scrapie brain homogenate
  incubated with Doxy, slows infectivity and
  increases survival time when hamster is
  transfected.

87
Case 2-Creutzfield-Jakob diseaseSummary

• 1. sCJD most common Prion disease, etio?
• 2. Rapidly fatal, non-infectious disease
• 3. Diagnosis of probable sCJD via characteristic
  MRI, EEG, anc clinical findings.
• 4. In appropriate clinical setting with high
  pre-test prob., CSF 14-3-3 has good sensitivity
  and good PPV.
• 5. Not person to person contagious. Inf control
  measures entail disposable instruments and
  universal precautions, and when necessary
  guideline driven sterilization/innactivation.