The Effect of Hypocretin Replacement Therapy in a 3-Year-Old Weimaraner with Narcolepsy
Bibliographic record
Abstract
A 3-year-old male neutered Weimaraner dog presented to the Cornell University Hospital for Animals with a chief complaint of acute onset cataplectic attacks, triggered by emotional events such as playing or eating.a The diagnosis of narcolepsy and cataplexy was made based on clinical signs and evaluation of cerebrospinal fluid (CSF) that contained a dramatically decreased hypocretin-1 concentration (Ͻ100 pg/mL; normal reference range, 200-350 pg/ mL). 1 To evaluate clinical signs on a repetitive basis during the course of treatment, the dog was trained to conduct food-elicited cataplexy tests (FECTs).a Both the number of attacks (NA) and elapsed time in collapse (ET) were measured as an index of cataplexy severity.Further supporting the diagnosis of narcolepsy and cataplexy, we measured a dramatic response to IV yohimbine (Figs 1, 2; NA and ET with no treatment: median, 6 collapses and 50.5 seconds, respectively; NA and ET with 0.048 g/kg IV: median, 0.5 collapses [P ϭ .004]and 9.5 seconds [P ϭ .005,Wilcoxon rank sum test], respectively). 2 Narcolepsy in dogs has been shown to affect more than 17 breeds. 3,4Two forms of the disease exist.In Doberman Pinschers, Labrador Retrievers, and Dachshunds, a familial form with early onset (Յ6 months of age) and autosomal recessive transmission has been reported.The familial form is caused by mutations in the hypocretin-receptor-2 gene. 5,6n most other cases, the disease is sporadic, the age of onset is variable, and the disease is associated with a loss of the hypocretin ligand. 7This more common form of narcolepsy in dogs is particularly interesting because it may be an equivalent of the human disorder.In humans, most cases are sporadic, with onset around adolescence, and patients typically have low concentrations of hypocretin-1 in CSF. 1 The disease in humans is associated closely with human leukocyte antigen HLA-DQ, and autoimmune destruction of hypocretincontaining cells has been proposed as the cause of the disorder. 8Studies have yet to demonstrate a DLA-DQ association in sporadic cases of narcolepsy in dogs.
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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 | 0.001 | 0.001 |
| 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".