P1‐134: Neurobehavioral characterization of adult‐onset alexander's disease: A family study
Bibliographic record
Abstract
Differentiating neurodegenerative disorders with prominent frontal impairment can be challenging. Alexander's disease is a clinically heterogenous condition associated with GFAP gene mutations that cause dysfunction of intermediate filaments, astrocytes, and neurons. In the adult-onset form of Alexander's disease (AoAD), there is brainstem degeneration with characteristic MRI features. The neurobehavioral changes in AoAD have not yet been clearly delineated. We present the neurobehavioral features of three siblings with suspected AoAD from a kindred with three affected generations. Descriptive clinical phenotypic study of a family with AoAD. An initial index case was identified, followed by neurobehavioral assessment of three siblings and family history documentation. Each of the affected siblings had MRI evidence of significant brainstem and cervical cord atrophy, consistent with AoAD. Sibling 1 (male, 58) presented with progressive ataxia and nystagmus at 47. Described changes in his behavior included withdrawal and apathy. He had predominant frontal executive dysfunction: impairment of set-shifting and mental flexibility; perseveration; flat affect; and anosagnosia. Other findings included verbal memory difficulties partially improved with cuing and ideomotor apraxia. He met diagnostic criteria for mild cognitive impairment (MCI) associated with AoAD. Sibling 2 (male, 53) presented with prominent mood and personality disturbances in his early 40s affecting his social and work function; his initial diagnosis was depression. He had primarily frontal dysfunction: impairments in concept formation and set-shifting; perseveration; abstraction; apathy; flat affect; and anosagnosia. Additionally, he had deficits in visual and verbal memory and temporal orientation, meeting criteria for dementia due to AoAD. Sibling 3 (female, 51) presented with mild ataxia at age 49, without behavioral complaints. She was noted on assessment to have inefficiency in working memory, attention, and memory retrieval, meeting criteria for MCI due to AoAD. We characterized AoAD in this family as including both cognitive impairment with frontal dysexecutive features, as well as significant early behavioral changes with frontal features, in the context of brainstem symptoms, including ataxia. The presenting neurobehavioral features raise consideration of frontotemporal dementia. Awareness of the phenotypic features of AoAD allows for more timely diagnoses, care, and genetic counseling for affected individuals and family members.
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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) | 0.000 | 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) | 0.000 | 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".