The fluctuating Connectome: Graph-Theoretical dissection of metabolic mimicry in Late-Onset ornithine transcarbamylase deficiency.

BACKGROUND

Rare metabolic epilepsies can clinically present as phenocopies of common focal or generalized syndromes. Graph-theoretical network analysis offers a non-invasive approach to characterising altered brain dynamics, but its application in late-onset metabolic encephalopathies remains largely unexplored.

METHODS

We conducted a proof-of-concept, single-case study evaluating longitudinal 19-channel scalp EEG functional connectivity in a patient with late-onset ornithine transcarbamylase (OTC) deficiency. Network metrics (global efficiency, characteristic path length, node degree) were derived during acute metabolic encephalopathy and following clinical stabilization. Statistical significance was evaluated using Crawford-Howell modified t-tests comparing the single patient against a normative reference cohort.

RESULTS

Preliminary findings demonstrated dynamic regional connectivity shifts in frontocentral sensor topologies during acute decompensation, which partially normalized following clinical management. Linear mixed-effects models accounting for epoch-level variability confirmed significant longitudinal trajectory alterations.

CONCLUSIONS

These preliminary, single-patient findings provide exploratory evidence that graph-theoretical metrics can track network shifts during metabolic decompensation in OTC deficiency. Given the single-case design, these observations cannot be generalized to metabolic phenocopies broadly and warrant future multi-center validation in larger metabolic cohorts.