Lawrence B. Schonberger, M.D., M.P.HPrion and Public Health Office,

Division of High-Consequence Pathogens & Pathology, National Center for Emerging &

Zoonotic Diseases

US-Diagnosed Variant Creutzfeldt-Jakob Disease in Two Patients Born and

Raised in Saudi Arabia

Division of High-Consequence Pathogens & Pathology

National Center for Emerging and Zoonotic Infectious Diseases

Characteristics of the Two vCJD Patients

Patient 1 Patient 2

Birth Country (yr) Saudi Arabia (1970) Saudi Arabia (1983)

Citizenship Saudi Arabia Egypt

Social Class “Professional” “Professional”

Country of vCJD onset (yr)

Saudi Arabia (2003) United States (2006)

Age at Onset 32.5 yrs. 22.8 yrs

Early Symptoms of the Two vCJD Patients

Patient 1 Patient 2

Increased irritability Numbness & “heat” sensation in

Withdrawn shoulders, legs, & thigh

Agitated Withdrawn

Paranoia Insomnia

Altered sleep/wake cycleIncreased anxiety (diagnosed by

psychiatrist)

Unsteady gait, scissor steps Unsteady gait, ataxia

Slurring of speech Emotionally labile, frequent crying

“Sensory symptoms”

Subsequent Dementia and Duration ofthe 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 soundsIncreased deep tendon reflexes,

ankle and jaw clonus

Illness duration: 6.9 years, mostly in

akinetic mute state; died in 2010.

Illness duration: 8.5 months; died in 2006

Diagnostic Test Results on the Two vCJD Patients

Test Patient 1 Patient 2

EEGNon-specific slow wave activity;

no periodic complexesDiffuse slowing;

no periodic complexes

MRI Positive pulvinar sign Positive pulvinar sign

PRNP GeneticsGenotype 129MM,

no mutationsGenotype 129MM,

no mutations

Adenoid BiopsyLymphoid follicles positive for

PrPsc; vCJD staining pattern

Brain BiopsyImmunopositive for PrPsc;

“Florid plaques”

Intense immunopositive deposits of PrPsc; Pericellular “encrustations” of stellate-

shaped cells with PrPsc

Results

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 0 - 27.25 32.5 - 5.25

United States

late 1997 – late 1998 27.25 - 28.3 5.25 – 4.2

Saudi Arabia

late 1998 – early 2003 (onset)

28.3 - 32.5 4.2 - 0

*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)

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

1983 - 1999 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 0.3 - 0

*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.

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.

Acknowledgments

T2 & Fluid-Attenuated Inversion-Recovery, FLAIR

“Pulvinar Sign”

MRI on Saudi vCJD Patient

Histopathological and Immunohistochemical Findings on Brain Biopsy of First Saudi vCJD Case compared to sCJD, 2004

A CB

A. H&E of a florid plaque in the present case. B. Immunostaining showing florid plaques.

C. Immunostaining of sCJDMM1 (B and C Mab 3F4).

50 µm

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)

Thank You!

For more information please contact Centers for Disease Control and Prevention

1600 Clifton Road NE, Atlanta, GA 30333Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348E-mail: cdcinfo@cdc.gov Web: http://www.cdc.gov

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

National Prion Disease Pathology Surveillance Center - Referrals, By Year of

Death

* Disease almost certainly acquired outside the US (UK or Saudi Arabia).

Year Referrals Prion disease (total) vCJD1996 & earlier 51 33 0

1997 114 68 0

1998 87 51 0

1999 122 74 0

2000 146 103 0

2001 209 119 0

2002 248 149 0

2003 274 176 0

2004 325 186 1*

2005 344 194 02006 382 196 2*2007 376 213 02008 396 232 02009 423 256 02010 403 251 0

Total 3900 2301 (59.5%) 3*