Drug resistant epilepsy case series

A retrospective database-driven cohort study of all patients with > 9 years follow-up at a single high-volume epilepsy center. Hsieh et al. included patients who underwent lobectomy, multilobar resection, or lesionectomy for drug-resistant epilepsy; they excluded patients who underwent hemispherectomy. The main outcomes were: 1. Reduction in frequency of disabling seizures (at 6 months, each year up to 9 years postoperatively, and at last follow-up). 2. Achievement of seizure remission (>6 months, >1 year, and longest duration). 3. Seizure freedom at the last follow-up.

They included 251 patients; 234 (93.2%) achieved 6 months, and 232 (92.4%) experienced 1 year of seizure freedom. Of these, the average period of seizure freedom was 10.3 years. 182 (72.5%) patients were seizure-free at the last follow-up (defined as > 1 year without seizures), with a median of 11.9 years since remission. For patients not completely seizure-free, the mean seizure frequency reduction at each timepoint was 76.2%, and ranged from 66.6% to 85.0%. Patients decreased their number of antiseizure medications on average by 0.58, and 53 (21.2%) patients were on no antiseizure medication at the last follow-up. Nearly half (47.1%) of those that seizure-free at the last follow-up were not seizure-free immediately postoperatively.

Patients who continue to have seizures after resection often have considerable reductions in seizure frequency, and many are able to achieve seizure freedom in a delayed manner 1).

Santos et al., performed (a) retrospective analysis of intraoperative AC-recordings of 69 patients and (b) a prospective study using intraoperative near-DC recording. All patients had the diagnosis of pharmaco-resistant epilepsy. Both studies were designed to determine the incidence and characteristics of spreading depolarizations (SDs) intraoperatively. In the retrospective analysis, they used intraoperative electrocorticography (iECoG) recordings obtained from AC-recording of 69 patients. In the prospective analysis, we used an Octal Bio Amp and Power Lab ECoG recorder with near-DC range.

In the retrospective study, we included 69 patients with a mean of 1 h 3 min of iECoG recordings. In the prospective study, we recruited 20 patients with near DC recordings. A total of 35 h 41 min of iECoG recordings with mean of 2 h 32 min/patient were analyzed. We did not find SD in either study.

SDs were not detected during intraoperative recordings of epilepsy surgery using AC- or DC-amplifiers 2).


20 children with refractory epilepsy were treated with tailored epilepsy surgery or vagus nerve stimulation (VNS). Wang et al. used the Engel Epilepsy Surgery Outcome Scale to evaluate seizure control and the Wechsler Intelligence Scale for Children, fourth edition (WISC-IV), to test the children's intellectual outcomes 7-day preoperative and 3-, 6-, and 12-month postoperative.

In total, 14 cases were seizure free (Engel I) and 2 cases to have suffered few attacks since surgery (Engel II). In two cases, the frequency of seizures decreased by >90% (Engel III). In the remaining two cases, the effects of surgery on seizure control were not obvious (Engel IV). All children completed the WISC-IV test. On average, postoperative intelligence quotient (IQ) increased by 6.35 points 12-month postsurgery compared with the results of the preoperative tests (P < 0.01). Second, intellectual outcomes after surgery in the Engel I and II groups increased by >3.88 points compared with in the Engel III and IV groups (P < 0.05). Finally, there were no fatal complications over the long-term follow-up except for intracranial infection of two cases; postoperative subcutaneous hematoma occurred in one case and hoarseness in one case.

Individualized epilepsy surgery is safe and effective for children with refractory epilepsy. It can control or reduce the frequency of postoperative attacks as well as improve postoperative intellectual outcomes to different degrees 3).


Carlson et al. from the Cedars-Sinai Medical Center reviewed the medical charts of 53 cases of medically refractory epilepsy operated on from 2006 to 2017, where both non-hybrid and hybrid microwire depth electrodes were used for intracranial monitoring. We assessed the localization accuracy and complications that arose to assess the relative safety and utility of hybrid depth electrodes compared with standard electrodes.

A total of 555 electrodes were implanted in 52 patients. The overall per-electrode complication rate was 2.3%, with a per-case complication rate of 20.8%. There were no infections or deaths. Serious or hemorrhagic complications occurred in 2 patients (0.4% per-electrode risk). Complications did not correlate with the use of any particular electrode type, and hybrids were equally as reliable as standard electrodes in localizing seizure onset zones.

Hybrid depth electrodes appear to be as safe and effective as standard depth electrodes for intracranial monitoring and provide unique opportunities to study the human brain at single-neuron resolution 4).


Resting-state fMRI data were gathered from 19 patients with refractory epilepsy (mixed localization and aetiologies) and 21 healthy people. The fMRI data were analyzed by group independent component analysis (ICA) fMRI toolbox to extract dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN). The components of the selected networks were compared between patients and healthy controls to explore the change in functional connectivity (FC). Granger causality analysis was performed by taking the aforementioned significant brain areas as regions of interest (ROIs) to calculate autoregression coefficients of each pair of ROIs. Comparisons were done to find the significantly different causal connectivity when FC was changed between patients and healthy controls.

RESULTS: In DAN, the FC values of the bilateral frontal eye field (FEF) and left intraparietal sulcus (IPS) were decreased. In VAN, the FC values of the double-side ventral prefrontal cortex (vPFC) and the temporoparietal junction (TPJ) were reduced. As for DMN, the FC values of the bilateral medial prefrontal cortices (mPFC) were decreased whereas those for the bilateral precuneus (PCUN) were increased. Granger causal connectivity values were correlated: causal influence was decreased significantly from the left IPS (in DAN) to the double side of the vPFC but remained the same for the right FEF (in DAN) to the right TPJ. The value was decreased from the left PCUN (in DMN) to the right TPJ and FEF, and the causal flow from the right PCUN to the right TPJ and bilateral vPFC was also significantly inhibited (p < 0.05).

Frequent seizures in patients with refractory epilepsy may damage the cortex and disturb DAN, VAN, and DMN, leading to functional and causal connectivity alteration. In addition, epileptic activity may disrupt network interactions and further influence information communication 5).


From 1987 to 1992, invasive EEG studies using subdural strips, subdural grids or depth electrodes were performed in a total of 160 patients with medically intractable epilepsy, in whom scalp EEG was insufficient to localize the epileptogenic focus. Dependent on the individual requirements, these different electrode types were used alone or in combination. Multiple strip electrodes with 4 to 16 contacts were implanted in 157 cases through burrholes, grids with up to 64 contacts in 15 cases via boneflaps, and intrahippocampal depth electrodes in 36 cases using stereotactic procedures. In every case, localization of the electrodes with respect to brain structures was controlled by CT scan and MRI. Visual and computerized analysis of extra-operative recordings allowed the localization of a resectable epileptogenic focus in 143 patients (89%), who subsequently were referred for surgery, whereas surgery had to be denied to 17 patients (11%). We did not encounter any permanent morbidity or mortality in our series. In our experience, EEG-monitoring with chronically implanted electrodes is a feasible technique which contributes essentially to the exact localization of the epileptogenic focus, since it allows nearly artefact-free recording of the ictal and interictal activity. Moreover, grid electrodes can be used for extra-operative functional topographic mapping of eloquent brain areas 6).


1)
Hsieh JK, Pucci FG, Sundar SJ, Kondylis E, Sharma A, Sheikh SR, Vegh D, Moosa AN, Gupta A, Najm I, Rammo R, Bingaman W, Jehi L. Beyond Seizure-Freedom: Dissecting Long-Term Seizure Control after Surgical Resection for Drug Resistant Epilepsy. Epilepsia. 2022 Oct 25. doi: 10.1111/epi.17445. Epub ahead of print. PMID: 36281562.
2)
Santos E, Dávila-Rodríguez DO, Márquez-Gonzalez K, Díaz-Peregrino R, Alonso-Vanegas M, Olivares-Rivera A, Anschel D, San-Juan D. Screening spreading depolarizations during epilepsy surgery. Acta Neurochir (Wien). 2019 Mar 9. doi: 10.1007/s00701-019-03870-z. [Epub ahead of print] PubMed PMID: 30852674.
3)
Erbay SH, Bhadelia RA, O'Callaghan M, Gupta P, Riesenburger R, Krackov W, Polak JF. Nerve atrophy in severe trigeminal neuralgia: noninvasive confirmation at MR imaging–initial experience. Radiology. 2006 Feb;238(2):689-92. PubMed PMID: 16436823.
4)
Carlson AA, Rutishauser U, Mamelak AN. Safety and Utility of Hybrid Depth Electrodes for Seizure Localization and Single-Unit Neuronal Recording. Stereotact Funct Neurosurg. 2018 Oct 16:1-9. doi: 10.1159/000493548. [Epub ahead of print] PubMed PMID: 30326475.
5)
Jiang LW, Qian RB, Fu XM, Zhang D, Peng N, Niu CS, Wang YH. Altered attention networks and DMN in refractory epilepsy: A resting-state functional and causal connectivity study. Epilepsy Behav. 2018 Sep 19;88:81-86. doi: 10.1016/j.yebeh.2018.06.045. [Epub ahead of print] PubMed PMID: 30243110.
6)
Behrens E, Zentner J, van Roost D, Hufnagel A, Elger CE, Schramm J. Subdural and depth electrodes in the presurgical evaluation of epilepsy. Acta Neurochir (Wien). 1994;128(1-4):84-7. PubMed PMID: 7847148.
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