Epilepsy affects an estimated ~3.4 million people in the United States and roughly 50 million worldwide. Unlike the morbidity-framed conditions in this atlas, epilepsy carries a genuine mortality endpoint: SUDEP — sudden unexpected death in epilepsy — the leading cause of epilepsy-related death, driven overwhelmingly by convulsive (generalised/bilateral tonic-clonic) seizures. This oracle estimates the causal reduction in SUDEP risk across pharmacological, surgical, neuromodulation and peri-ictal-rescue options, using effect sizes from named trials. For education, not individual medical advice.
Tick the interventions to combine. Each shows its trial effect estimate, 95% confidence interval (CI), E-value, mechanism, and citation. ★ = in the current Pareto effective set but not yet ticked.
Headline is the front-door estimate: shared GTCS overlap removed via dose-response saturation; residual direct-effect overlap removed via the eigenvalue model at ρ̄.
Under monotonicity + exogeneity (E-value bounds the exogeneity assumption).
Faithful causal directed acyclic graph (DAG). Seizure-suppression therapies act through the shared mediator convulsive (GTCS) seizure burden, which drives the peri-ictal cardio-respiratory collapse that terminates in SUDEP (Y). Nocturnal supervision and detection devices act independently of seizure frequency — they shorten time-to-rescue on the collapse→death transition. Named confounders — syndrome, drug-resistance severity, intellectual disability — open back-door paths (adjusted). Mediator cascade: interventions attach to the node they act on (anti-seizure → surgery / → adherence /), which converge on the disease state and thence the endpoint — drawing the intermediate mediators explicitly is what exposes d-separation and per-channel saturation.
Eigenvalue diagnostics for the selected interventions under an equicorrelation matrix (off-diagonal ρ̄). A large λmax relative to k signals redundancy; n_eff is the effective number of independent interventions actually contributing.
On mechanistic grounds ρ̄ ≈ 0.30 is defensible: the drug/surgery/neuromodulation options overwhelmingly share one final common pathway — reducing convulsive-seizure burden toward freedom — so stacking two seizure-suppression modalities is partly redundant. ρ̄ is user-adjustable because a rescue device shares essentially no mechanism with a seizure medication. Most of the overlap is now handled structurally by the mediator nodes (same-node substitutes saturate); ρ̄ governs only the residual correlation among direct effects.
Minimum-effective-set analysis. Set a target combined risk reduction; the model finds the smallest set of interventions — accounting for front-door mediator overlap — that reaches it, and highlights them. If the target exceeds what all interventions together can achieve, the full set is shown (never an empty one). "Apply" ticks exactly that set.
Monte Carlo propagation. Each selected intervention's log-effect is sampled from a normal distribution implied by its 95% CI; samples are combined with the same eigenvalue overlap discount. 5,000 draws.
Intervening on the selected set S with Pearl's do-operator (setting the interventions, not merely observing them). Contrast against do(∅) = no intervention.
For each intervention: "if not for this one, the combined front-door effect would be…". Isolates each intervention's marginal causal contribution after mediator-overlap removal, so shared-pathway agents are not double-credited.
| If not for… | RR without it | RR with full set | marginal RRR lost |
|---|
One-at-a-time sensitivity. Each intervention's effect is swung across its 95% confidence interval (others held at point estimate); the bar is the resulting swing in the combined front-door effect. A long bar means the combined estimate leans heavily on that single trial's precision.
Front-door (mediation) decomposition. Seizure-suppression therapies act through one shared mediator — convulsive (GTCS) seizure burden. Each log-effect is split into a convulsive-burden-mediated (indirect) and a frequency-independent (direct) part. Indirect parts are pooled through the mediator with dose-response saturation, removing the mediator cross-correlation; direct parts keep the residual eigenvalue correlation at ρ̄. Nocturnal supervision and detection devices, which avert death without reducing seizures, are NOT discounted against the seizure-suppression options. Here mediated effects are pooled WITHIN each cascade node (dose-response saturation of substitutes) and composed in SERIES across nodes (d-separated channels), with the per-node reductions reported so the channel structure is visible.
| Intervention | RR | %GTCS | med-frac | indirect log | direct log |
|---|
Which % of cross-correlation is appropriate? Not one number. The mediator overlap is fixed empirically by the GTCS saturation (currently removing — of the summed mediated effect when interventions are stacked). Note a domain caveat: seizure-suppression options are partly redundant (shared freedom pathway), whereas rescue interventions are additive because they act on a different step. Convulsive-burden mediated fractions are transparent, adjustable priors.
Front-door caveat (antithesis): the endpoint is SUDEP — driven by convulsive seizures only, so for focal-only epilepsy the mediator carries almost no mortality signal (OR ~1.15). SUDEP is rare in absolute terms, VNS survival benefit is contested (CI crosses 1), and the surgical effect is candidate-selected and attenuates after ~10 years.
Select interventions to generate a plain-language summary.