Introduction
Methods
Patients and database
CSF tests
Statistical analyses
Results
General description
Forms of gTSE | Number of cases total (female gender) | Percentage of neuropatho-logically confirmed cases (n) | Age at onset, years, median (range) | Clinical duration, months, median (range) | Codon 129 polymorphism | PrP type I | ||
---|---|---|---|---|---|---|---|---|
MM % (n) | MV % (n) | VV % (n) | ||||||
gCJD | 124 (68) | |||||||
E200K | 64 (37) | 54.7 (35) | 59 (29–86) | 6 (0.43–34) | 63.5 (33) | 36.5 (19) | 0.0 (0) | 4/4 |
V210I | 40 (19) | 47.5 (19) | 56.5 (43–87) | 4 (1–31) | 67.5 (27) | 32.5 (13) | 0.0 (0) | 5/5 |
Other | 20 (12) | 28.6 (6) | 65 (32–77) | 6.5 (2–12) | 37.5 (6) | 31.3 (5) | 31.3 (5) | 3/3 |
FFI | 23 (5) | 87 (20) | 56 (24–83) | 12.5 (1–97) | 60.9 (14) | 39.1 (9) | 0.0 (0) | |
GSS | 10 (4) | 22 (2) | 50 (25–70) | 80.5 (54–87) | 30.0 (3) | 60.0 (6) | 10.0 (1) | |
A117V | 1 | |||||||
P102L | 8 | |||||||
P105L | 1 | |||||||
Insert gTSE | 17 (11) | 52.9 (9) | 63 (36–77) | 11 (3–19) | 46.7 (7) | 33.3 (5) | 20.0 (3) | 1/1 |
Quantitative levels of brain-derived proteins
Abnormal cerebrospinal fluid findings in gTSEs
14-3-3
14-3-3 | Tau | S100b | NSE | |
---|---|---|---|---|
gCJD | 83.0 (97/117) | 86.4 (38/44) | 87.0 (20/23) | 64.3 (18/28) |
E200K | 80.3 (49/61) | 75.0 (15/20) | 92.9 (13/14) | 45.4 (5/11) |
V210I | 85.0 (34/40) | 100 (13/13) | 100 (4/4) | 75.0 (6/8) |
D178N-Val | 33.3 (1/3) | 100 (1/1) | 0.0 (0/1) | 100.0 (1/1) |
R208H | 100 (3/3) | 100 (2/2) | 100.0 (1/1) | |
V203I | 100 (2/2) | |||
E211Q | 100 (2/2) | 100 (2/2) | 100 (1/1) | 100 (1/1) |
E196K | 100 (2/2) | 100 (3/3) | 100 (2/2) | 100 (3/3) |
T188K | 100 (2/2) | 100 (1/1) | 50.0 (1/2) | |
G114V | 0.0 (0/1) | 0.0 (0/1) | 0.0 (0/1) | 0.0 (0/1) |
R148H | 100 (1/1) | 100 (1/1) | ||
Insert gTSE | 68.8 (11/16) | 80.0 (12/15) | 77.8 (7/9) | 50.0 (4/8) |
GSS | 10.0 (1/10) | 40.0 (2/5) | 50.0 (2/4) | 0.0 (0/2) |
A117V | 0.0 (0/1) | 0.0 (0/1) | 0.0 (0/1) | |
P102L | 12.5 (1/8) | 66.7 (2/3) | 100 (2/2) | 0.0 (0/2) |
P105L | 0.0 (0/1) | 0.0 (0/1) | 0.0 (0/1) | |
FFI | 13.0 (3/23) | 7.1 (1/14) | 20.0 (2/10) | 0.0 (0/12) |
Stratification by codon 129 genotype | ||||
E200K | ||||
MM | 78.1 (25/32) | |||
MV | 88.2 (15/17) | |||
VV | 0.0 (0/0) | |||
V210I | ||||
MM | 77.8 (21/27) | p = 0.06 | ||
MV | 100.0 (13/13) | |||
VV | 0.0 (0/0) | |||
Others | ||||
MM | 100.0 (6/6) | |||
MV | 80.0 (4/5) | |||
VV | 50.0 (2/4) |
Tau
S100b
NSE
Effect of octapeptide repeats
Effects of patient characteristics on abnormal findings
Characteristics | Number of 14-3-3 positive patients/total | Number of tau positive patients/total | Number of S100b positive patients/total | Number of NSE positive patients/total |
---|---|---|---|---|
Age at onset | ||||
<40 | 1/4 | 1/1 | 1/1 | 1/1 |
40–60 | 47/57 | 18/19 | 9/11 | 11/15 |
60–80 | 46/53 | 18/21 | 9/9 | 6/11 |
>80 | 2/2 | 1/1 | – | – |
p-value | 0.016 | 0.76 | 0.34 | 0.47 |
Codon 129 | ||||
MM | 52/65 | 22/22 | 7/8 | 9/12 |
MV | 32/35 | 11/14 | 9/10 | 6/12 |
VV | 2/4 | 2/2 | 1/1 | 2/2 |
p value | 0.075 | 0.06 | 0.93 | 0.25 |
Disease duration | ||||
> median | 22/26 | 10/11 | 5/5 | 7/9 |
< median | 48/55 | 21/21 | 9/10 | 8/12 |
p value | 0.74 | 0.16 | 0.46 | 0.58 |
Time point of LP during diseasea
| ||||
Early stage | 8/8 | 1/1 | 1/1 | 0/1 |
Middle stage | 23/26 | 7/7 | 3/3 | 3/3 |
Advanced stage | 28/34 | 7/7 | 3/3 | 2/2 |
p value | 0.40 | – | – | 0.17 |
Author | Journal | Mutation |
n
| 14-3-3 | tau | nse | S100b |
---|---|---|---|---|---|---|---|
E200K | |||||||
Rosenmann [18] | Neurology 1999 | E200K | 16 | 94% | |||
Cataldi [4] | Neurol Sci 2000 | E200K | 1 | + | |||
Kovacs [11] | Hum Gen 2005 | E200K | 62 | 89% | |||
Sanchez-Valle [23] | Eur J Neurol 2004 | E200K | 5 | 100% | |||
Ladogana [15] | Neurology 2005 | E200K V210I | 95 | 81% in MM, 95% in MV + in VV | |||
V210I | |||||||
Kovacs [11] | Hum Gen 2005 | V210I | 35 | 100% | |||
Huang [7] | Arq neuropsiquiatr 2001 | V210I | 1 | – | |||
D178N | |||||||
Zerr [30] | Neurology 1998 | D178N-129M | 8 | – | |||
Sanchez-Valle [23] | Eur J Neurol 2004 | D178N-129M | 2 | 0% | |||
Kovacs [11] | Hum Gen 2005 | D178N 129V | 22 | 10% | |||
Rosenmann [18] | Neurology 1999 | D178N 129V | 1 | + | |||
Zarranz [29] | JNNP 2005 | D178N | 4 | 0% 50% | |||
129MM | 2 | ||||||
D178N +MV | |||||||
Rosenmann [19] | Acta Neurol Scand 1998 | D178N-129V | 2 | + | |||
P102L | |||||||
Imaiso [8] | Rinsho Shinkeigaku 1998 | P102L | 1 | + | Elevated | ||
Kovacs [11] | Hum Gen 2005 | P102L | 7 | 57% | |||
Others | |||||||
Krebs [13] | Neurogenetics 2005 | R148H | 1 | + | |||
Iwaski [9] | Rinsho Shinkeigaku. 1999 | V180I | 1 | Not done | 30 | ||
Collins [5] | Arch Neurol 2000 | T188A | 1 | + | |||
Kotta [10] | BMC Infect dis 2006 | T193I | 1 | + | |||
Tumani [25] | DMW 2002 | E196K | 1 | + | Elevated | Elevated | |
Capellari [3] | Neurology 2005 | R208H | 1 | + | |||
Roeber [17] | Acta Neuropathol 2005 | R208H | 1 | + | |||
Ladogana [14] | Am J Med Gen 2001 | E211Q | 1 | + | |||
Sanchez-Vallez [22] | JNNP 2008 | 9OPRI | 1 | − |