Rationale: Lissencephaly type 1 is characterized by a smooth cerebral cortex, profound developmental delay, and intractable epilepsy. Historically, patients with lissencephaly have been excluded from surgical consideration due to poor localizability and the potential for adverse outcomes[1]. However, the emergence of minimally invasive techniques has begun to challenge this traditional perspective. We present a case of a 19-year-old female with lissencephaly type 1 and Lennox-Gastaut syndrome (LGS) who achieved seizure freedom following a complete laser callosotomy. Remarkably, the procedure resulted in no neurological deficits, alongside notable improvements in mood and overall health.
Methods:
The patient had a history of severe epilepsy since birth, with seizures that were refractory to multiple antiseizure medications, vagus nerve stimulation (VNS), and the ketogenic diet. Preoperative evaluation included a comprehensive seizure history, electroencephalography (EEG), and neuroimaging, which confirmed the diagnosis of lissencephaly type 1. Prior to surgery, the patient experienced over 200 tonic seizures per day, severely disrupting her sleep-wake cycle. This led to significant weight loss, increased susceptibility to infections, and frequent hospitalizations. Given the failure of medical therapies and the severity of her epilepsy, the patient underwent a minimally invasive complete laser callosotomy.
Results:
Postoperatively, the patient experienced complete seizure freedom, along with restoration of her sleep-wake cycle and a level of alertness and positive affect that, according to her parents, had never been observed before. She has remained seizure-free and has not required hospitalization since the procedure. There were no new neurological deficits or decline in function relative to her preoperative baseline. Interestingly, the therapeutic effect was not immediate, but evolved gradually over weeks, suggesting a delayed mechanism of action.
Conclusions:
This case challenges the longstanding view against surgical intervention in patients with lissencephaly type 1 and refractory epilepsy. The achievement of complete seizure freedom, coupled with the absence of new neurological deficits following a minimally invasive laser callosotomy, supports reconsideration of surgical candidacy in this traditionally excluded population. The delayed therapeutic response prompts important questions about the underlying mechanisms. One hypothesis is that partial yet sufficient disconnection of transhemispheric fibers initiates Wallerian degeneration, which may gradually disrupt pathological network synchrony and diminish interhemispheric epileptogenicity. Further research is warranted to delineate the subsets of patients with lissencephaly who may benefit from such interventions. This case highlights that with modern, minimally invasive techniques, the traditional paradigm of surgical exclusion may no longer be applicable—and that transformative outcomes are possible in carefully selected individuals.
References:
1.Sakakibara-Berger E, et al. Total callosotomy ameliorates epileptic activity and improves cognitive function in a patient with Miller-Dieker syndrome. Cell Rep Med. 2024;5(5):101361.
Funding: N/A