Table 1
Clinical and Demographic Features of Human Prionopathies in the Published Literature
| 164 | 23 | 12 | 45 | 30 | 50 | ||
|---|---|---|---|---|---|---|---|
| Age at onset (y), median (IQR) | 62 (54, 69) | 36 (26, 41) | 45.5 (37, 52.5) | 60 (46, 68) | 45 (34, 53) | 48 (37, 56) | <0.001 |
| Disease duration (m), median (IQR) | 7 (4, 15.5) | 17 (10, 18) | 9.5 (6.5, 12) | 5 (4, 16) | 11 (9, 13) | 58.5 (30, 96) | <0.001 |
| Cognitive/Behavioral | <0.001 | ||||||
| Onset | 95 (57.9%) | 18 (78.3%) | 8 (66.7%) | 34 (75.6%) | 10 (33.3%) | 29 (58%) | |
| Later in course | 38 (23.2%) | 4 (17.4%) | 4 (33.3%) | 9 (20%) | 18 (60%) | 16 (32%) | |
| Not reported | 31 (18.9%) | 1 (4.3%) | 0 (0%) | 2 (4.4%) | 2 (6.7%) | 5 (10%) | |
| Movement Disorders | <0.001 | ||||||
| Onset | 89 (54.3%) | 6 (26.1%) | 8 (66.7%) | 14 (31.1%) | 10 (33.3%) | 30 (60%) | |
| Later in course | 73 (44.5%) | 17 (73.9%) | 4 (33.3%) | 30 (66.7%) | 20 (46.7%) | 18 (36%) | |
| Not reported | 2 (1.2%) | 0 (0%) | 0 (0%) | 1 (2.2%) | 0 (0%) | 2 (4%) | |
| Dysautonomia | <0.001 | ||||||
| Onset | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 5 (16.7%) | 0 (0%) | |
| Later in course | 1 (0.6%) | 0 (0%) | 1 (8.3%) | 7 (15.6%) | 16 (53.3%) | 0 (0%) | |
| Not reported | 163 (99.4%) | 23 (100%) | 11 (91.7%) | 38 (84.4%) | 9 (30%) | 50 (100%) | |
| Sleep disorder | <0.001 | ||||||
| Onset | 2 (1.2%) | 0 (0%) | 1 (8.3%) | 7 (15.7%) | 19 (63.3%) | 0 (0%) | |
| Later in course | 1 (0.6%) | 0 (0%) | 0 (0%) | 5 (10%) | 8 (26.6%) | 0 (0%) | |
| Not reported | 161 (98.2%) | 23 (100%) | 11 (91.7%) | 33 (73.3%) | 3 (10%) | 50 (100%) |
[i] Abbreviations: FFI, Fatal Familial Insomnia; gCJD, Genetic Creutzfeldt–Jakob Disease; GSS, Gerstmann–Sträussler–Scheinker Disease; iCJD, Iatrogenic Creutzfeldt–Jakob Disease; IQR, Interquartile Range; p-value, Wilcoxon rank sum test for continuous data and chi-square test for categorical data; sCJD, Sporadic Creutzfeldt–Jakob Disease; vCJD, Variant Creutzfeldt–Jakob Disease.
Table 2
Prevalence of Movement Disorders in Human Prionopathies
| 164 | 23 | 12 | 45 | 30 | 50 | ||
|---|---|---|---|---|---|---|---|
| Gait ataxia | 103 (62.8%) | 21 (91.3%) | 9 (75%) | 30 (66.7%) | 17 (56.7%) | 37 (74%) | 0.051 |
| Limb ataxia | 66 (40.2%) | 9 (39.1%) | 7 (58.3%) | 24 (53.3%) | 8 (26.7%) | 10 (20%) | 0.012 |
| Myoclonus | 96 (58.5%) | 13 (56.5%) | 8 (66.7%) | 32 (71.1%) | 20 (66.7%) | 12 (24%) | <0.001 |
| Tremor | 8 (4.9%) | 2 (8.7%) | 1 (8.3%) | 3 (6.7%) | 4 (13.3%) | 4 (8%) | 0.47 |
| Parkinsonism | 12 (7.3%) | 2 (8.7%) | 1 (8.3%) | 7 (15.6%) | 4 (13.3%) | 9 (18%) | 0.24 |
| Rigidity | 72 (43.9%) | 7 (30.4%) | 3 (25%) | 26 (57.8%) | 7 (23.3%) | 20 (40%) | 0.037 |
| Chorea | 6 (3.7%) | 7 (30.4%) | 0 (0%) | 0 (0%) | 0 (0%) | 2 (4%) | <0.001 |
| Dystonia | 15 (9.1%) | 2 (8.7%) | 0 (0%) | 1 (2.2%) | 0 (0%) | 2 (4%) | 0.28 |
| Gaze palsy | 18 (11%) | 3 (13%) | 1 (8.3%) | 1 (2.2%) | 0 (0%) | 0 (0%) | 0.011 |
[i] Abbreviations: FFI, Fatal Familial Insomnia; gCJD, Genetic Creutzfeldt–Jakob Disease; GSS, Gerstmann–Sträussler–Scheinker Disease; iCJD, Iatrogenic Creutzfeldt–Jakob Disease; p-value, Fisher’s exact test; sCJD, Sporadic Creutzfeldt–Jakob Disease; vCJD, Variant Creutzfeldt–Jakob Disease.
Table 3
Time (Months) from Movement Disorder Onset until Death
| sCJD | vCJD | iCJD | gCJD | FFI | GSS | p-value | |
|---|---|---|---|---|---|---|---|
| Gait ataxia, median (IQR) | 5 (2, 12) | 8 (6, 18) | 7 (6, 8) | 4.5 (4, 10) | 9 (5, 12) | 56 (13, 84) | <0.001 |
| Limb ataxia, median (IQR) | 4 (2, 12) | 7 (6, 18) | 6 (4, 13) | 5 (3, 9.5) | 5.5 (3.5, 18.5) | 58.5 (48, 72) | 0.017 |
| Myoclonus, median (IQR) | 2 (2, 4.5) | 6 (3, 12) | 4.5 (2, 9) | 4 (2, 10) | 5 (3, 8) | 5.5 (2.5, 71) | 0.025 |
| Tremor, median (IQR) | 3 (1.5, 7) | 23.5 (12, 35) | 10 (10, 10) | 4 (4, 60) | 9.5 (5, 13) | 31.5 (2, 84) | 0.57 |
| Parkinsonism, median (IQR) | 3 (3, 13.5) | 4.5 (1, 8) | 10 (10, 10) | 18 (16, 90) | 8.5 (5.5, 18) | 36 (24, 65) | 0.100 |
| Rigidity, median (IQR) | 5.5 (2, 12.5) | 17 (7, 18) | 13 (8, 13) | 5 (4, 16) | 9 (5, 17) | 42 (9.5, 102) | 0.002 |
| Chorea, median (IQR) | 14 (4, 27) | 3 (2, 8) | - | - | - | 2. (2, 3) | 0.12 |
| Dystonia, median (IQR) | 2 (2, 6) | 14.5 (11, 18) | - | 3 (3, 3) | - | 60.5 (1, 120) | 0.48 |
| Gaze palsy, median (IQR) | 8.5 (2, 14) | 8 (7, 14) | 13 (13, 13) | 16 (16, 16) | - | - | 0.71 |
[i] Abbreviations: FFI, Fatal Familial Insomnia; gCJD, Genetic Creutzfeldt–Jakob Disease; GSS, Gerstmann–Sträussler–Scheinker Disease; iCJD, Iatrogenic Creutzfeldt–Jakob Disease; IQR, Interquartile Range; p-value, Wilcoxon rank sum test; sCJD, Sporadic CJD; vCJD, Variant Creutzfeldt–Jakob Disease.
Table 4
Difference in Clinical Features in gCJD with and without E200K Mutation
| gCJD E200K+(n = 19) | gCJD E200K-(n = 26) | p-value | |
|---|---|---|---|
| Age at presentation (years), median (IQR) | 54 (46, 64) | 60.5 (47, 73) | 0.32 |
| Total disease duration (months), median (IQR) | 4 (2, 5) | 12 (4, 22) | <0.001 |
| Cognitive/Behavioral | 0.15 | ||
| Initial presentation, N (%) | 12 (63%) | 22 (85%) | |
| Later in course, N (%) | 6 (32%) | 3 (11%) | |
| Not reported, N (%) | 1 (5%) | 1 (4%) | |
| Movement Disorders | 0.35 | ||
| Initial presentation, N (%) | 8 (42%) | 6 (23%) | |
| Later in course, N (%) | 11 (58%) | 19 (73%) | |
| Not reported, N (%) | 0 (0%) | 1 (4%) | |
| Dysautonomia | 0.015 | ||
| Initial presentation, N (%) | 0 (0%) | 0 (0%) | |
| Later in course, N (%) | 4 (21%) | 2 (8%) | |
| Not reported, N (%) | 15 (79%) | 24 (92%) | |
| Sleep disorder | 0.019 | ||
| Initial presentation, N (%) | 6 (32%) | 1 (4%) | |
| Later in course, N (%) | 0 (0%) | 3 (11%) | |
| Not reported, N (%) | 13 (68%) | 22 (85%) | |
| Presence of movement disorders | |||
| Gait ataxia, N (%) | 18 (95%) | 12 (46%) | <0.001 |
| Limb ataxia, N (%) | 16 (84%) | 8 (31%) | <0.001 |
| Myoclonus, N (%) | 14 (74%) | 18 (69%) | 1.00 |
| Tremor, N (%) | 0 (0%) | 3 (11%) | 0.25 |
| Parkinsonism, N (%) | 0 (0%) | 7 (27%) | 0.016 |
| Rigidity, N (%) | 13 (68%) | 13 (50%) | 0.24 |
| Chorea, N (%) | 0 (0%) | 0 (0%) | |
| Dystonia, N (%) | 1 (5%) | 0 (0%) | 0.42 |
| Gaze palsy, N (%) | 0 (0%) | 1 (4%) | 1.00 |
[i] Abbreviations: gCJD, Genetic Creutzfeldt–Jakob Disease; IQR, Interquartile Range; p-value, Wilcoxon rank sum test for continuous data and Fisher’s exact test for categorical data.
E200K- group included the following mutations to the PRNP gene, E196K; D178N/129V; G114K; M232R; P105T; R208H; T183A; T188R and V180I.
Table 5
Difference in Clinical Features in GSS with and without P102L Mutation
| GSS P102L+(n = 33) | GSS P102L-(n = 17) | p-value | |
|---|---|---|---|
| Age at presentation (y), mean (IQR) | 50 (38, 56) | 47 (37, 60) | 0.67 |
| Total disease duration ( s), mean (IQR) | 56 (30, 84) | 72 (30, 120) | 0.47 |
| Cognitive/Behavioral | 0.059 | ||
| Initial presentation, N (%) | 16 (49%) | 13 (76%) | |
| Later in course, N (%) | 13 (39%) | 3 (18%) | |
| Not reported, N (%) | 4 (12%) | 1 (6%) | |
| Movement Disorders | 0.047 | ||
| Initial presentation, N (%) | 23 (70%) | 7 (41%) | |
| Later in course, N (%) | 8 (24%) | 10 (59%) | |
| Not reported, N (%) | 2 (6%) | 0 (0%) | |
| Dysautonomia | |||
| Not reported N (%) | 33 (100%) | 17 (100%) | |
| Sleep disorder | |||
| Not Reported N (%) | 33 (100%) | 17 (100%) | |
| Movement disorders | |||
| Gait ataxia, N (%) | 26 (79%) | 11 (65%) | 0.32 |
| Limb ataxia, N (%) | 6 (18%) | 4 (24%) | 0.72 |
| Myoclonus, N (%) | 5 (15%) | 7 (41%) | 0.077 |
| Tremor, N (%) | 2 (6%) | 2 (12%) | 0.60 |
| Parkinsonism, N (%) | 2 (6%) | 7 (41%) | 0.004 |
| Rigidity, N (%) | 11 (33%) | 9 (53%) | 0.23 |
| Chorea, N (%) | 1 (3%) | 1 (6%) | 1.00 |
| Dystonia, N (%) | 0 (0%) | 2 (12%) | 0.11 |
| Gaze palsy, N (%) | 0 (0%) | 0 (0%) |
[i] Abbreviations: GSS, Gerstmann–Sträussler–Scheinker Disease; IQR, Interquartile Range; p-value, Wilcoxon rank sum test for continuous data and Fisher’s exact test for categorical data.
P102L-group included the following mutations to the PRNP gene: A117V, D202N, G131V, H187R, P84S, Q212P, Q217R, 6 and 7 octapeptide repeat insertions.
Table 6
Subtypes of Sporadic Creutzfeldt–Jakob Disease
| Subtype* (frequency) | Age of onset Years (range) | Duration Months (range) | Presentation | Movement disorders | Regions predominantly affected |
|---|---|---|---|---|---|
| MM1/MV1(65%) | 68 (31–86) | 5 (1–24) | Cognitive/behavioral, visual changes | Ataxia Myoclonus | Neocortex (particularly occipital lobe), subcortical nuclei and cerebellum |
| VV2(20%) | 64 (40–83) | 6.5 (3–18) | Cerebellar dysfunction. Later, cognitive/behavioral changes | Gait and limb ataxia Oculomotor abnormalities | Cerebellum and subcortical nuclei |
| MV2(10%) | 65 (36–83) | 17 (4–48) | Cognitive/behavioral or motor | Ataxia Parkinsonism Myoclonus | Cerebellum and subcortical nuclei. Less cortical involvement |
| MM2 (Thalamic)(<5%) | 52 (26–71) | 16 (8–36) | Insomnia, cognitive | Ataxia Myoclonus | Thalamus and inferior olive |
| MM2 (Cortical)(<5%) | 64 (49–77) | 16 (9–36) | Cognitive, apraxia, aphasia | Myoclonus | Neocortex |
| VV1(1%) | 44 (19–55) | 21 (17–42) | Cognitive/behavioral | Ataxia Parkinsonism | Cortex and striatum |
* Subtypes are based on the combination of methionine/valine polymorphism at codon 129 in the PRNP (MV, MM, VV) and the electrophoresis pattern of PrP after the exposure of prion protein to proteinase K digestion (classified as 1 or 2).
Frequency, age of onset, and duration values for this table were obtained from literature review.