Long-term Outcome of Resective Epilepsy Surgery in Patients With Lennox-Gastaut Syndrome

Kang, Joon Won; Eom, Soyong; Hong, William; Kwon, Hye Eun; Park, Soyoung; Ko, Ara; Kang, Hoon Chul; Lee, Joon Soo; Lee, Young Mock; Kim, Do Kyung; Kim, Heung Dong

doi:10.1542/peds.2018-0449

Cited by 26 publications

(45 citation statements)

References 24 publications

(18 reference statements)

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“…The finding that cortical involvement precedes thalamic participation in GPFA is consistent with our recent DCM analysis of EEG‐fMRI in LGS, 4 which found that GPFA was more likely to be initiated by prefrontal cortex than either thalamus or brain stem. It is also consistent with our prior single photon emission computed tomography study of tonic seizures showing early blood flow changes in prefrontal cortex and the pontine region of the brain stem, 16 and the known phenomenon that cortical lesions can cause LGS, whereas their removal can abolish seizures 5,17 . Given our findings of widespread scalp EEG changes at GPFA onset, prior to thalamic involvement, it appears that mechanisms apart from the thalamus may be responsible for initiating epileptic activity across diffuse cortical regions.…”

Section: Discussionsupporting

confidence: 91%

“…It is also consistent with our prior single photon emission computed tomography study of tonic seizures showing early blood flow changes in prefrontal cortex and the pontine region of the brain stem, 16 and the known phenomenon that cortical lesions can cause LGS, whereas their removal can abolish seizures. 5,17 Given our findings of We did not find an effect of "pathway" (ie, different pairs of scalp and thalamic electrode contacts) on PTE values, nor an interaction between brain state and pathway.…”

Section: Discussionmentioning

confidence: 50%

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Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox‐Gastaut syndrome

et al. 2020

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We aimed to assess the roles of the cortex and thalamus (centromedian nucleus [CM]) during epileptic activity in Lennox-Gastaut syndrome (LGS) patients undergoing deep brain stimulation (DBS) surgery as part of the ESTEL (Electrical Stimulation of the Thalamus for Epilepsy of Lennox-Gastaut Phenotype) trial. Methods: Twelve LGS patients (mean age = 26.8 years) underwent bilateral CM-DBS implantation. Intraoperatively, simultaneous electroencephalogram (EEG) was recorded (range = 10-34 minutes) from scalp electrodes and bilateral thalamic DBS electrodes. Temporal onsets of epileptic discharges (generalized paroxysmal fast activity [GPFA] and slow spike-and-wave [SSW]) were manually marked on recordings from scalp (ie, "cortex") and thalamus (ie, CM-DBS electrodes). Phase transfer entropy (PTE) analysis quantified the degree of information transfer from cortex to thalamus within different frequency bands around GPFA events. Results: GPFA was captured in eight of 12 patients (total event number across patients = 168, cumulative duration = 358 seconds). Eighty-six percent of GPFA events were seen in both scalp and thalamic recordings. In most events (83%), onset occurred first at scalp, with thalamic onset lagging by a median of 98 milliseconds (interquartile range = 78.5 milliseconds). Results for SSW were more variable and seen in 11 of 12 patients; 25.4% of discharges were noted in both scalp and thalamus. Of these, 74.5% occurred first at scalp, with a median lag of 75 milliseconds (interquartile range = 228 milliseconds). One to 0.5 seconds and 0.5-0 seconds before GPFA onset, PTE analysis showed significant energy transfer from scalp to thalamus in the delta (1-3 Hz) frequency band. For alpha (8-12 Hz) and beta (13-30 Hz) frequencies, PTE was greatest 1-0.5 seconds before GPFA onset. Significance: Epileptic activity is detectable in CM of thalamus, confirming that this nucleus participates in the epileptic network of LGS. Temporal onset of GPFA mostly occurs earlier at the scalp than in the thalamus. This supports our prior EEGfunctional magnetic resonance imaging results and provides further evidence for a cortically driven process underlying GPFA in LGS.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 50%

Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox‐Gastaut syndrome

et al. 2020

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“…Resective surgery is a treatment option in LGS patients with focal pathology and there is a high probability of seizure control in about 50% of patients following surgery 32 . Patients are carefully identified for resective surgery based on congruent findings of a definitive structural lesion using electroencephalogram (EEG), magnetic resonance imaging (MRI), and functional neuroimaging.…”

Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulation in patients with Lennox‐Gastaut syndrome: A meta‐analysis

et al. 2020

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Objectives Lennox‐Gastaut syndrome (LGS) is among the most severe epileptic and developmental encephalopathies. A meta‐analysis was performed to evaluate the effectiveness of adjunctive vagus nerve stimulation (VNS Therapy) in patients with LGS. Materials & Methods PubMed database was queried (January 1997 to September 2018) to identify publications reporting on the efficacy of VNS Therapy in patients with LGS, with or without safety findings. Primary endpoint of the meta‐analysis was the proportion of responders (≥50% reduction in seizure frequency). Random‐effects analysis was used to calculate weighted mean estimates and confidence intervals. Heterogeneity was evaluated by statistical tests including I2. Results Of 2752 citations reviewed, 17 articles (480 patients) were eligible including 10 retrospective studies and seven prospective studies. A random‐effects model produced a pooled proportion of 54% (95% confidence intervals [CI]: 45%, 64%) of patients with LGS who responded to adjunctive VNS Therapy (p for heterogeneity <0.001, I2=72.9%). Per an exploratory analysis, the calculated incidence of serious adverse events associated with VNS Therapy was 9% (95% CI: 5%, 14%); the rate was higher than in long‐term efficacy studies of heterogeneous cohorts with drug‐resistant epilepsy and likely attributed to variable definitions of serious adverse events across studies. Conclusions The meta‐analysis of 480 patients with LGS suggests that 54% of patients responded to adjunctive VNS Therapy and that the treatment option was safe and well‐tolerated. The response in patients with LGS was comparable to heterogeneous drug‐resistant epilepsy populations. A clinical and surgical overview has been included to facilitate the use of VNS in LGS.

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“…38 Among resective surgery studies, shorter duration of preoperative epilepsy and hemispherectomy were associated with better seizure outcomes. 21,66 53 Common measures included parental or caregiver rating, 56,59,63 Weschler Intelligence Scale for Children, 53,61,65 and visual analogue scale. 56,61 Five studies 29,36,54,59,64 noted specific improvements in alertness for a majority of their LGS patients after VNS.…”

Section: Prognostic Factorsmentioning

confidence: 99%

The role of surgery in the management of Lennox–Gastaut syndrome: A systematic review and meta‐analysis of the clinical evidence

Thirunavu

et al. 2021

Epilepsia

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Lennox–Gastaut syndrome (LGS) is a severe form of childhood onset epilepsy in which patients require multiple medications and may be candidates for palliative surgical intervention. In this meta‐analysis, we sought to evaluate the impact of palliative vagus nerve stimulation (VNS), corpus callosotomy (CC), and resective surgery (RS) by analyzing their impact on seizure control, antiepileptic drug (AED) usage, quality of life (QOL), behavior, cognition, prognostic factors, and complications. A systematic search of PubMed MEDLINE, Scopus, and Cochrane Database of Systematic Reviews was performed to find articles that met the following criteria: (1) prospective/retrospective study with original data, (2) at least one LGS surgery patient aged less than 18 years, and (3) information on seizure frequency reduction (measured as percentage, Engel class, or qualitative comment). Seizures were analyzed quantitatively in a meta‐analysis of proportions and a random‐effects model, whereas other outcomes were analyzed qualitatively. Forty studies with 892 LGS patients met the selection criteria, with 19 reporting on CC, 17 on VNS, four on RS, two on RS + CC, one on CC + VNS, and one on deep brain stimulation. CC seizure reduction rate was 74.1% (95% confidence interval [CI] = 64.5%–83.7%), and VNS was 54.6% (95% CI = 42.9%–66.3%), which was significantly different (p < .001). RS seizure reduction was 88.9% (95% CI = 66.1%–99.7%). Many VNS patients reported alertness improvements, and most had no major complications. VNS was most effective for atonic/tonic seizures; higher stimulation settings correlated with better outcomes. CC patients reported moderate cognitive and QOL improvements; disconnection syndrome, transient weakness, and respiratory complications were noted. Greater callosotomy extent correlated with better outcomes. AED usage most often did not change after surgery. RS showed considerable QOL improvements for patients with localized seizure foci. In the reported literature, CC appeared to be more effective than VNS for seizure reduction. VNS may provide a similar or higher level of QOL improvement with lower aggregate risk of complications. Patient selection, anatomy, and seizure type will inform decision‐making.

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Long-term Outcome of Resective Epilepsy Surgery in Patients With Lennox-Gastaut Syndrome

Abstract: Resective surgery is a viable option in some patients to treat seizures that are associated with LGS, with a high probability of seizure control and better adaptive function.

Cited by 26 publications

References 24 publications

Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox‐Gastaut syndrome

Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox‐Gastaut syndrome

Vagus nerve stimulation in patients with Lennox‐Gastaut syndrome: A meta‐analysis

The role of surgery in the management of Lennox–Gastaut syndrome: A systematic review and meta‐analysis of the clinical evidence

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