1. Lawrence B. Schonberger, M.D., M.P.H
US-Diagnosed Variant Creutzfeldt-Jakob Disease in Two Patients Born and Raised in Saudi Arabia
Lawrence B. Schonberger, M.D., M.P.H
Prion and Public Health Office, Division of High-Consequence Pathogens & Pathology, National Center for Emerging & Zoonotic Diseases
National Center for Emerging and Zoonotic Infectious Diseases
Division of High-Consequence Pathogens & Pathology

2. Characteristics of the Two vCJD Patients
Birth Country (yr)
Saudi Arabia (1970)
Saudi Arabia (1983)
Citizenship
Saudi Arabia
Egypt
Social Class
“Professional”
Country of vCJD onset (yr)
Saudi Arabia (2003)
United States (2006)
Age at Onset
32.5 yrs.
22.8 yrs

3. Early Symptoms of the Two vCJD Patients
Increased irritability
Numbness & “heat” sensation in
Withdrawn
shoulders, legs, & thigh
Agitated
Paranoia
Insomnia
Altered sleep/wake cycle
Increased anxiety (diagnosed by psychiatrist)
Unsteady gait, scissor steps
Unsteady gait, ataxia
Slurring of speech
Emotionally labile, frequent crying
“Sensory symptoms”

4. Subsequent Dementia and Duration of the Two vCJD Illnesses
Patient 1
Patient 2
Within 10 months of onset:
Within 6 months of onset:
“Global cognitive impairment”
Severe dementia
Decreased verbal output
Non-ambulatory
Making incomprehensible sounds
Increased deep tendon reflexes, ankle and jaw clonus
Illness duration: years, mostly in
akinetic mute state; died in 2010.
Illness duration: 8.5 months; died in 2006

5. Diagnostic Test Results on the Two vCJD Patients
EEG
Non-specific slow wave activity; no periodic complexes
Diffuse slowing; no periodic complexes
MRI
Positive pulvinar sign
Positive pulvinar sign
PRNP Genetics
Genotype 129MM, no mutations
Adenoid Biopsy
Lymphoid follicles positive for PrPsc; vCJD staining pattern
Brain Biopsy
Immunopositive 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 Onset
Country*
Calendar Years
Age (yrs)
Intervals before Onset (yrs)
Saudi Arabia
1970- late 1997
United States
late 1997 – late 1998
5.25 – 4.2
late 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 Onset
Country*
Calendar Years
Age (yrs)
Intervals before Onset (yrs)
Saudi Arabia
0 - 16
23 - 7
Egypt
1999 – late 2005
16 – 22.5
7 – 0.3
United States
late 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. Acknowledgments
Pathologist Pierluigi Gambetti and his staff at the National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA
Professors Robert Will and Richard Knight and their staff at the UK CJD Surveillance Unit, Edinburgh, Scotland, UK
Neurologist Michael Geschwind and Pathologist Stephen DeArmond and their staff at the University of California, San Francisco, USA
State Epidemiologists and their staff at the Arizona, California, North Carolina and Virginia State Departments of Health, USA
Neurologists Shireen A. Qureshi, Saudi Arabia and Alireza Atri, USA
Pathologist Caterina Giannini, Mayo Clinic, Minnesota, USA
Dr. Imad A. Al Jahdall, Chief Preventive Medicine Services Division, Saudi Aramco Medical Services Organization, Dhahran, Saudi Arabia
Colleagues 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, 2004 A C B
H&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 Prevention
1600 Clifton Road NE, Atlanta, GA
Telephone: 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 Diseases
Division of High-Consequence Pathogens & Pathology

13. National Prion Disease Pathology Surveillance Center - Referrals, By Year of Death
Prion disease (total)
vCJD
1996 & earlier 51 33
1997
114 68
1998 87
1999
122 74
2000
146
103
2001
209
119
2002
248
149
2003
274
176
2004
325
186 1*
2005
344
194
2006
382
196 2*
2007
376
213
2008
396
232
2009
423
256
2010
403
251
Total
3900
2301 (59.5%) 3*
* Disease almost certainly acquired outside the US (UK or Saudi Arabia).