Presentation on theme: "Lawrence B. Schonberger, M.D., M.P.H"— Presentation transcript:
1 Lawrence B. Schonberger, M.D., M.P.H US-Diagnosed Variant Creutzfeldt-Jakob Disease in Two Patients Born and Raised in Saudi ArabiaLawrence B. Schonberger, M.D., M.P.HPrion and Public Health Office, Division of High-Consequence Pathogens & Pathology, National Center for Emerging & Zoonotic DiseasesNational Center for Emerging and Zoonotic Infectious DiseasesDivision of High-Consequence Pathogens & Pathology
2 Characteristics of the Two vCJD Patients Birth Country (yr)Saudi Arabia (1970)Saudi Arabia (1983)CitizenshipSaudi ArabiaEgyptSocial Class“Professional”Country of vCJD onset (yr)Saudi Arabia (2003)United States (2006)Age at Onset32.5 yrs.22.8 yrs
3 Early Symptoms of the Two vCJD Patients Increased irritabilityNumbness & “heat” sensation inWithdrawnshoulders, legs, & thighAgitatedParanoiaInsomniaAltered sleep/wake cycleIncreased anxiety (diagnosed by psychiatrist)Unsteady gait, scissor stepsUnsteady gait, ataxiaSlurring of speechEmotionally labile, frequent crying“Sensory symptoms”
4 Subsequent Dementia and Duration of the Two vCJD Illnesses Patient 1Patient 2Within 10 months of onset:Within 6 months of onset:“Global cognitive impairment”Severe dementiaDecreased verbal outputNon-ambulatoryMaking incomprehensible soundsIncreased deep tendon reflexes, ankle and jaw clonusIllness duration: years, mostly inakinetic mute state; died in 2010.Illness duration: 8.5 months; died in 2006
5 Diagnostic Test Results on the Two vCJD Patients EEGNon-specific slow wave activity; no periodic complexesDiffuse slowing; no periodic complexesMRIPositive pulvinar signPositive pulvinar signPRNP GeneticsGenotype 129MM, no mutationsAdenoid BiopsyLymphoid follicles positive for PrPsc; vCJD staining patternBrain BiopsyImmunopositive for PrPsc;“Florid plaques”Intense immunopositive deposits of PrPsc; Pericellular “encrustations” of stellate-shaped cells with PrPsc
6 Intervals before Onset (yrs) Countries of Residence of 1st US-Diagnosed vCJD Patient by Calendar Years, Age, and Time Intervals Before vCJD OnsetCountry*Calendar YearsAge (yrs)Intervals before Onset (yrs)Saudi Arabia1970- late 1997United Stateslate 1997 – late 19985.25 – 4.2late 1998 – early (onset)*Visited United Kingdom for 4 days in late 1997 and France for 1 and/or 2 weeks in 1995 and/or 1996 (Maximum interval before vCJD onset, 8.1 years)
7 Intervals before Onset (yrs) Countries of Residence of 2nd US-Diagnosed vCJD Patient by Calendar Years, Age, and Time Intervals Before vCJD OnsetCountry*Calendar YearsAge (yrs)Intervals before Onset (yrs)Saudi Arabia0 - 1623 - 7Egypt1999 – late 200516 – 22.57 – 0.3United Stateslate 2005 – early 2006 (onset)22.5 – 22.8*Visited the United States for 1½ months in 1989 and since 2001, occasionally during vacations each year for up to about 3 months at a time.
8 AcknowledgmentsPathologist Pierluigi Gambetti and his staff at the National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USAProfessors Robert Will and Richard Knight and their staff at the UK CJD Surveillance Unit, Edinburgh, Scotland, UKNeurologist Michael Geschwind and Pathologist Stephen DeArmond and their staff at the University of California, San Francisco, USAState Epidemiologists and their staff at the Arizona, California, North Carolina and Virginia State Departments of Health, USANeurologists Shireen A. Qureshi, Saudi Arabia and Alireza Atri, USAPathologist Caterina Giannini, Mayo Clinic, Minnesota, USADr. Imad A. Al Jahdall, Chief Preventive Medicine Services Division, Saudi Aramco Medical Services Organization, Dhahran, Saudi ArabiaColleagues at the Centers for Disease Control and Prevention, Atlanta, Georgia, USA, particularly members of the Prion and Public Health Office, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases.
9 MRI on Saudi vCJD Patient T2 & Fluid-Attenuated Inversion-Recovery, FLAIR“Pulvinar Sign”
10 Histopathological and Immunohistochemical Findings on Brain Biopsy of First Saudi vCJD Case compared to sCJD, 2004ACBH&E of a florid plaque in the present case.Immunostaining showing florid plaques.Immunostaining of sCJDMM1 (B and C Mab 3F4).
11 B: magnification 40X – US Patient PrP IHC Plaque-like and spider-like formations; HE of the location of the plaque-like formations is unremarkable (mAb 3F4)
12 Thank You!For more information please contact Centers for Disease Control and Prevention1600 Clifton Road NE, Atlanta, GATelephone: CDC-INFO ( )/TTY:Web:The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.National Center for Emerging and Zoonotic Infectious DiseasesDivision of High-Consequence Pathogens & Pathology
13 National Prion Disease Pathology Surveillance Center - Referrals, By Year of Death Prion disease (total)vCJD1996 & earlier5133199711468199887199912274200014610320012091192002248149200327417620043251861*200534419420063821962*2007376213200839623220094232562010403251Total39002301 (59.5%)3** Disease almost certainly acquired outside the US (UK or Saudi Arabia).