Coricobasal Syndrome: Clinical, Neuropsychological, Imaging, Genetic and Pathological Features
Bibliographic record
Abstract
Corticobasal Syndrome (CBS) is a rare movement and cognitive disorder. There is significant heterogeneity observed in it clinical presentation, neuroimaging, pathology and genetics. Understanding this heterogeneity is a priority and may help to shed light on underlying pathogenic mechanisms. We first demonstrated that truncating mutations in the progranulin gene (PGRN) can cause familial CBS associated with frontotemporal lobar degeneration (FTLD)-ubiquitin pathology. This study identified a mutation in PGRN (Intervening Sequence 7+1 guanine > adenine [IVS7+1G>A]) that segregated with CBS in a family. The mutation was predicted to result in a shortened messenger RNA (mRNA) sequence and the absence of the mutant PGRN allele was confirmed in the reverse transcriptase-polymerase chain reaction (RT-PCR) product, which supported the model of haploinsufficiency for PGRN-linked disease. In a second familial study, clinical, radiological, genetic, and pathological studies were performed to contrast clinical features of the affected members. Sequencing PGRN revealed a novel, heterozygous cytosine-adenine dinucleotide deletion in exon 11 (g.2988_2989delCA, P439_R440fsX6). The proband`s clinical diagnosis was frontotemporal dementia and parkinsonism (FTDP). The proband’s brother with the same mutation presented initially as a progressive non-fluent aphasia (PNFA), and later evolved into a CBS. Pathological analysis revealed Frontotemporal Lobar Degeneration-Ubiquitin (FTLD-U)/ TAR DNA-binding protein 43 (TDP43) positive pathology. The next studies shift away from pathogenic mechanisms to focus on brain-behavioural correlations and phenotypic heterogeneity in a prospective sample of 31 CBS cases. We provide the first direct correlative analysis between the severity of ideomotor apraxia, a common sign in CBS, and cerebral SPECT perfusion imaging. Reductions in perfusion within the left inferior parietal lobule (t=5.7, p=0.03, Family-Wise Error [FWE] corrected), including the left angular gyrus (t=5.7, p=0.02, FWE corrected), were associated with more severe ideomotor apraxia. We stratified the sample into CBS presenting with early motor features (CBS-M; n=9) or early dementia (CBS-D; n=22), which identified that CBS-M were more likely to have cortical sensory loss than CBS-D (p=0.005). In contrast, the presence of aphasia was found to be more common and severe in CBS-D compared to CBS-M (p=0.02). CBS-M patients had significantly reduced perfusion in the right supplementary and premotor areas compared to CBS-D (p<0.05).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.012 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".