Apparent Cerebellar Volumetric Stabilization and Emergent Cortical Hyperexcitability During Long-Acting Injectable Aripiprazole Maintenance in Adolescent Bipolar Disorder

Background and Clinical Significance: This report investigates the complex intersection of macrostructural neuroprotection and cortical hyperexcitability during long-acting atypical antipsychotic maintenance. We present a novel clinical case demonstrating an apparent absence of detectable cerebellar vermis atrophy progression during long-acting injectable (LAI) aripiprazole maintenance, which temporally coincided with the emergence of a potential epileptogenic risk in an adolescent with bipolar disorder (BD) and cannabis use disorder. Beyond motor precision, the vermis modulates emotional-cognitive networks; deficits in these circuits impair impulse control, frequently driving comorbid substance use in youth. Case Presentation: A 16-year-old female with BD and cannabis use disorder presented with pronounced cerebellar and vermis atrophy on brain CT during an acute behavioral crisis. Following diagnostic reformulation, maintenance therapy was initiated via off-label monthly LAI aripiprazole (400 mg) alongside lithium. At 9-month follow-up, psychiatric relapses and cannabis use remitted completely. Repeat CT suggested macrostructural stability with zero apparent atrophy progression. However, during the 9th month, she abruptly developed daily generalized myoclonus. An awake electroencephalogram (EEG) revealed intense cortical hyperexcitability, documenting frequent interictal and ictal epileptiform discharges with generalized 3–4 Hz spike-wave complexes synchronized with the clinical myoclonus. Introduction of levetiracetam (500 mg BID) and cessation of adjunct methylphenidate led to complete clinical and neurophysiological remission. Conclusions: LAI aripiprazole may favorably influence the macrostructural trajectory of the cerebellum/vermis in adolescent BD, suggesting volume stabilization. However, clinicians must monitor for a drug-induced lowering of the seizure threshold, where macrostructural volume preservation coexists with microstructural electrical destabilization.