Novel neuropathological observations in an adult with Dravet syndrome
Bibliographic record
Abstract
Dravet syndrome (DS) is a developmental and epileptic encephalopathy associated with pathogenic variants in the SCN1A gene. The neuropathological features of adult DS remain poorly understood. We report the postmortem findings of a 55-year-old woman with DS due to a confirmed SCN1A pathogenic variant leading to Nav1.1 loss of function. Clinically, she developed pharmacoresistant seizures, intellectual disability, progressive ataxia, parkinsonism, and cognitive decline. Neuropathological examination revealed a striking excess and several layers of corpora amylacea (wasteosomes) covering the whole convexity of the brain. In addition, abundant p62-positive gray matter neuritic profiles were found mostly in limbic regions and in the white matter in neocortical regions. Pericellular TMEM106B-positive deposits and prominent immunoreactivity for aquaporin 4 were also observed. There was severe Purkinje cell loss in some lobes of the cerebellum together with variable neuronal loss in the substantia nigra, neocortex, and hippocampus. No α-synuclein, amyloid-β, or phospho-TDP-43 pathology was present. Immunostaining for phosphorylated tau revealed neurofibrillary pathology consistent with Braak stage I (left) -II (right). In summary, our study reveals pathological alterations suggestive of chronic glymphatic insufficiency, impaired autophagy, and some degree of neuronal loss without currently known misfolded protein deposits. These findings are suggestive of an accelerated aging and neurodegenerative process in this adult with DS.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".