Abstracts

Rationale: Many patients with the most common form of 15q duplication syndrome (dup15q syndrome), isodicentric or pseudoisodicentric dup15q syndrome, present with developmental and epileptic encephalopathy (DEE). Outcomes of epilepsy treatment in this population remain highly variable, and further investigation to determine effective therapeutic options is necessary. We present 3 patients with DEE associated with dup15q syndrome effectively treated with neurostimulation devices.


Methods: Institutional records were reviewed for current patients with dup15q syndrome diagnoses. Three patients were identified. Demographics, seizure history, and treatment outcomes were reported and analyzed.


Results: Demographics, seizure types & severity, ASMs and responses to neuromodulations are summarized in Table 1. All three patients were referred to neurology initially for global developmental delay - hypotonia, inability to sit or walk independently and minimal to no words. They subsequently developed explosive onset at ages 2-5 years of multiple daily seizures or status epilepticus evolving to Lennox-Gastaut Syndrome with tonic seizures refractory to numerous antiseizure medications (ASMs). Number of ASMs tried in each patient were 4, 6, and 7; while the current number of ASMs is 3, 4, and 3 + ketogenic diet. Cannabidiol (CBD,15mg/kg/day) was helpful in all 3 patients, while rufinamide (RUF, 40mg/kg/day) and lamotrigine (LTG, 5-8mg/kg/day) were helpful in reducing seizures in two patients. Two patients received vagal nerve stimulation (VNS) and one patient, responsive neurostimulation (RNS) at age 3, the youngest reported case of central medial thalamic nucleus (CMT) RNS. All reported significant benefit from placement of the device; they had over 90% reduction in their seizures. Two patients subsequently were able to discontinue two ASMs without increased seizure burden. All became more alert, responsive and interactive and were able to stand or walk with assistance.


Conclusions: We present 3 patients with severe DEE related to dup15q syndrome effectively treated with neurostimulation. All experienced significant improvement of their epileptic encephalopathy. To our knowledge, a dramatic response to neuromodulation in dup15q syndrome has not been previously reported. A positive response to LTG and RUF is consistent with prior literature, but CBD has not been previously identified as a consistently effective ASM in this population. The developmental progression observed with effective therapy particularly emphasizes the critical importance of early and aggressive intervention. While further research is needed to identify which antiseizure therapies are consistently most effective in dup15q syndrome, this case series suggests that early initiation of presurgical evaluation and neurostimulation may be beneficial in this population.


Funding: None