Table e-1: Clinical and demographic in each subject group.
Patients groups / Number (M:F) / Mean age±SD
(median;range) / Mean time (months)
first symptom to MRI scan
±SD
(median, range) / MMSE
±SD
(median, range) / Barthel
±SD
(median, range) / PRNP Mutation / Diagnostic criteria
sCJD / 48
(23:25) / 63±11
(62, 40-81) / 8.5±7.6
(6.7, 0.4-36.5) / 13±10
(17, 0-28) / 56±32
(60) / 43/48 tested:
all negative / In 41 path-proven cases,e1 (codon 129 polymorphism: 26 MM,12 MV, 3 VV.
In 32 cases, prion type:
11 type 1, 17 type 2, 4 type 1 and 2)
In 7 non-pathology proven cases,aWHO criteria e2
fCJDb / 6 / 60±15
(52, 48-85) / 28.3±45
(10.3, 0.8-118.7) / 15±10
(13, 4-28) / 87±6
(90, 80-90) / 3 E200K
1 V180I
1 D178N (codon 129 VV)
1, 5-OPRI
GSSc / 7 / 43±15
(44, 23-64) / 35±10
(35.7, 12-50) / 17±10
(18, 5-27) / 60±33
(60, 20-100) / 1 P102L
4 A117V
2 F198S
npRPDd / 29 / 61±8
(61, 45-73) / 15±18
(9, 1-83) / 19±9
(22, 0-30) / 74±29
(80, 0-100) / 13/29
tested: all negative
a 5 probable sCJD subjects (WHO criteria) lived less than 9 months from first symptom. 2 subjects lived less than 2.5 years and had elevated CSF NSE (>35 ng/ml) and total-tau (> 1200 pg/ml) levels
b for fCJD, MMSE data for 5 subjects, Barthel for 3 subjects
c2 GSS subjects technically asymptomatic and their data not included in time to scan, MMSE and Barthel data. Barthel data from 4 subjects.
dfor npRPD subjects, MMSE data on 22, Barthel on 12, subjects
OPRI = octapeptide repeat insertion
e-References
e1.Kretzschmar HA, Ironside JW, DeArmond SJ, Tateishi J. Diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Arch Neurol 1996;53(9):913-920.
e2.WHO. Global surveillance, diagnosis and therapy of human transmissible spongiform encephalopathies: Report of a WHO consultation. In: World Health Organization: Emerging and other communicable diseases, surveillance and control; 1998 9-11 February; Geneva, 1998.
npRPD diagnostic groups / Specific diagnosis / Total(N=29) / Path-proven
(N = 14) / Serologically or genetic provena
(N=5)
Neurodegenerative dementiasb / Total / 12 / 5
Corticobasal degeneration / 3 / 1
Frontotemporal dementia / 3 / 2
Alzheimer’s disease / 2 / 2
Dementia with Lewy Bodies / 2
Parkinson’s disease / 1
Unknown dementia / 1
Autoimmune or paraneoplastic encephalopathy / Total / 9 / 5 / 4
Antibody-mediated neuro-autoimmune disorderc / 4 / 3 / 4
Hashimoto’s encephalopathyd / 2
Sarcoidosis / 1 / 1
metastatic non-CNS Hodgkin’s lymphoma / 1 / 1
Multiple sclerosise / 1
Vascular dementias / Strokesf / 2
Tumors / CNS lymphoma / 2 / 2
Infectious / Meningoencephalitisg / 2 / 2
Toxic- Metabolic / Total / 2 / 1
Alcoholic encephalopathyh / 1
MELASi / 1 / 1
a N.B. Three serologically-proven cases were also pathologically-proven (two paraneoplastic antibody subjects with lung cancer and a VGKC-associated encephalopathy with negative brain biopsy for prion disease).
b Non pathology-proven neurodegenerative conditions met accepted probable diagnostic criteria 1-4and survived longer than 3.5 years and/or improved with treatment (e.g., acetylcholinesterase inhibitors for DLB). Subject with unknown dementia had rapid onset of memory loss with partial seizures, but has stabilized with greater than 10 years (and no PRNP mutation). 4 of 6 neurodegenerative subjects were tested, and negative, for PRNP mutations.
cone patient each with anti-GAD65 Ab,5 VGKC Ab 6, or anti-CV2 Ab (SCLC)and one with both anti-AMPAR and Sox2 Abs,7. The VGKC subject had a negative brain biopsy for prion disease. The two paraneoplastic cases had pathology-proven lung cancers. All autoimmune subjects improved dramatically with treatment, except one (Anti-GAD) whom only stabilized.
d Had elevated anti-thyroperoxidase or anti-thyroglobulin antibodies and improved with immunosuppressive treatment8.
eSubject had MS cerebellitis with ataxia and behavioral problems and improved with treatment.
f subjects improved from embolic stroke and temporal lobe stroke
g One enterovirus 9 and the other unspecified, but non-prion by pathology
hImproved dramatically for a few years before declining
iGene mutation identified
Table e-2, supplemental data: Diagnostic data of control subjects with non-prion rapidly progressive dementia (npRPD)
e-References
1.Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, et al. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. Neurology 1997;48(1):119-125.
2.McKeith IG. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J Alzheimers Dis 2006;9(3 Suppl):417-423.
3.Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51(6):1546-1554.
4.McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34(7):939-944.
5.Chang CC, Eggers SD, Johnson JK, Haman A, Miller BL, Geschwind MD. Anti-GAD antibody cerebellar ataxia mimicking Creutzfeldt-Jakob disease. Clin Neurol Neurosurg 2007;109:54-57.
6.Geschwind MD, Tan KM, Lennon VA, Barajas RF, Jr., Haman A, Klein CJ, et al. Voltage-gated potassium channel autoimmunity mimicking Creutzfeldt-Jakob disease. Arch Neurol 2008;65(10):1341-1346.
7.Lai M, Hughes EG, Peng X, Zhou L, Gleichman AJ, Shu H, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009.
8.Chong JY, Rowland LP. What's in a NAIM? Hashimoto encephalopathy, steroid-responsive encephalopathy associated with autoimmune thyroiditis, or nonvasculitic autoimmune meningoencephalitis? Arch Neurol 2006;63(2):175-176.
9.Valcour V, Haman A, Cornes S, Lawall C, Parsa AT, Glaser C, et al. A case of enteroviral meningoencephalitis presenting as rapidly progressive dementia. Nat Clin Pract Neurol 2008;4(7):399-403.
Patterns of gray matter regions / Percent of cases / Percent of cases (grouped as in1)A / Neocortex + Limbic + Subcortical / 54 / 63
B / Limbic + Subcortical / 9
C / Neocortex + Limbic / 27 / 31
D / Neocortex / 4
E / Neocortex + Subcortical / 4 / 4
F / Subcortical / 2 / 2
Total / 100 / 100
Tablee-3, supplemental data: Percentage of sCJD patients presenting with each of six patterns of gray matter abnormalities
e-References
1.Young GS, Geschwind MD, Fischbein NJ, Martindale JL, Henry RG, Liu S, et al. Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt-Jakob disease: high sensitivity and specificity for diagnosis. AJNR Am J Neuroradiol 2005;26(6):1551-1562.