Teaching LLMs to Recommend and Defer in Underrepresented Epilepsy Care
Authors: Shreyas Rajesh, Kartik Sharma, Tonmoy Monsoor, Mehmet Yigit Turali, Richard Idro, Juliana Kayaga, Robert Sebunya, Tracy Tushabe Namata, +3 more
Abstract
Specialist epilepsy expertise is scarce in resource-constrained settings, making LLM-based decision support attractive for frontline clinicians managing longitudinal treatment. Such systems must adapt to local prescribing practice and know when to defer. We study this problem in Ugandan pediatric epilepsy care, predicting anti-seizure medication regimens from longitudinal unstructured clinic notes. Standard prompting achieves non-trivial agreement with physician prescriptions, but neurologist review shows that many errors reflect distribution-miscalibrated prescribing defaults rather than failures to parse the local record. We introduce MANANA, a non-parametric prompt-learning framework that learns local prescribing guidance from a small patient-level training set. MANANA converts observed prescription errors into auditable prompt memories, instantiated in single-agent and multi-agent variants, and improves over classical ML models, direct LLM prompting, and prompt-optimization baselines across two independently collected Ugandan cohorts. We further propose Bayesian prompt averaging, which converts the learned prompt trajectory into prescription likelihoods and an uncertainty-based deferral signal. On the independently collected held-out cohort, this improves visit-level top-3 prescription accuracy by 4-8 percentage points over prompt-optimization baselines and enables selective prediction: the system can auto-handle the most confident half of cases at 95% precision, or the most confident quarter at 99% precision, while deferring lower-confidence cases for specialist review.
Inpatient medication recommendation requires clinicians to repeatedly select specific medications, doses, and routes as a patient's condition evolves. Existing benchmarks formulate this task as admission-level prediction over coarse drug codes with multi-hot diagnostic and procedure code inputs, failing to capture the per-timepoint, information-rich nature of real prescribing. We propose RxEval, a prescription-level benchmark that evaluates LLM prescribing capability by multiple-choice questions: each question presents a detailed patient profile and time-ordered clinical trajectory, requiring selection of specific medication-dose-route triples from real prescriptions and patient-specific distractors generated via reasoning-chain perturbation. RxEval comprises 1,547 questions spanning 584 patients, 18 diagnostic categories, and 969 unique medications. Evaluation of 16 LLMs shows that RxEval is both challenging and discriminative: F1 ranges from 45.18 to 77.10 across models, and the best Exact Match is only 46.10%. Error analysis reveals that even frontier models may overlook stated patient information and fail to derive clinical conclusions.
Epilepsy diagnosis and treatment require evidence-intensive reasoning across heterogeneous clinical knowledge, including biosignal patterns, genetic mechanisms, pharmacogenomics, treatment strategies, and patient outcomes. In this work, we present \textsc{EpiGraph}, a large-scale epilepsy knowledge graph and benchmark for evaluating knowledge-augmented clinical reasoning. \textsc{EpiGraph} integrates 48,166 peer-reviewed papers and seven clinical resources into a heterogeneous graph containing 24,324 entities and 32,009 evidence-grounded triplets across five clinical layers. Built upon this graph, \textsc{EpiBench} defines five clinically motivated tasks spanning clinical decision-making, EEG report generation, pharmacogenomic precision medicine, treatment recommendation, and deep research planning. We evaluate six LLMs under both standard and Graph-RAG settings. Results show that integrating \textsc{EpiGraph} consistently improves performance across all tasks, with the largest gains observed in pharmacogenomic reasoning (+30--41%). Our findings demonstrate that structured epilepsy knowledge substantially enhances evidence-grounded clinical reasoning and provides a practical benchmark framework for evaluating knowledge-augmented LLMs in real-world neurological settings. Our code is available at: https://github.com/LabRAI/EEG-KG.
Drug recommendation requires a deep understanding of individual patient context, especially for complex conditions like Parkinson's disease. While LLMs possess broad medical knowledge, they fail to capture the subtle nuances of actual prescribing patterns. Existing RAG methods also struggle with these complexities because guideline-based retrieval remains too generic and similar-patient retrieval often replicates majority patterns without accounting for the unique clinical nuances of individual patients. To bridge this gap, we propose PACE-RAG (Patient-Aware Contextual and Evidence-Constrained RAG). Rather than directly copying frequent medications from retrieved patients, PACE-RAG personalizes recommendations by first extracting patient-specific clinical features, retrieving cases around these features, and then refining the final prescription using the patient's current symptoms, active medication history, and focus-specific prescribing tendencies. By analyzing treatment patterns tailored to specific clinical features, PACE-RAG generates patient-specific medication recommendations along with an explainable clinical summary. PACE-RAG achieved the strongest performance among the evaluated inference-only LLM-based methods, reaching F1 scores of 80.84% and 47.22% on the Parkinson's disease and MIMIC-IV cohorts, respectively. Our code is available at: https://github.com/ChaeYoungHuh/PACE-RAG.