Francesco Cardinale and Massimo Cossu
Massimo Cossu, Marco Schiariti, Stefano Francione, Dalila Fuschillo, Francesca Gozzo, Lino Nobili, Francesco Cardinale, Laura Castana and Giorgio Lo Russo
The authors report on the use of stereoelectroencephalography (stereo-EEG) in the presurgical electroclinical evaluation of infants and very young children with focal drug-resistant epilepsy.
Fifteen patients (9 girls and 6 boys, mean age 34.1 ± 7.3 months, range 21–45 months), potentially candidates to receive surgical treatment for their focal drug-resistant epilepsy, were evaluated using stereo-EEG recording for a detailed definition of the epileptogenic zone. Stereoelectroencephalography was indicated because neuroradiological (brain MRI) and video-EEG data failed to adequately localize the epileptogenic zone. Stereotactic placement of multicontact intracerebral electrodes was preceded by the acquisition of all pertinent anatomical information from structural and functional MRI and from brain angiography, enabling the accurate targeting of desired structures through avascular trajectories. Stereoelectroencephalography monitoring attempted to record habitual seizures; electrical stimulations were performed to induce seizures and for the functional mapping of eloquent areas. Stereoelectroencephalography-guided microsurgery, when indicated, pointed to removal of the epileptogenic zone and seizure control.
Brain MRI revealed an anatomical lesion in 13 patients (lobar in 2 cases, multilobar or hemispheric in 11 cases) and was unremarkable in 2 patients. One patient underwent 2 stereo-EEG studies. The arrangement of the intracerebral electrodes was unilateral in all but 1 case. One patient died the day following electrode placement due to massive brain edema and profound hyponatremia of undetermined cause. In 8 cases intracerebral electrical stimulations allowed mapping of functionally critical areas; in 3 other cases that received purposeful placement of electrodes in presumably eloquent areas, no functional response was obtained. Of the 14 patients who completed stereo-EEG monitoring, 1 was excluded from surgery for multifocality of seizures and 13 underwent operations. Postoperatively, 2 patients exhibited an anticipated, permanent motor deficit, 3 experienced a transient motor deficit, and 2 experienced transient worsening of a preexisting motor deficit. Three patients developed a permanent homonymous hemianopia after posterior resections. Histological analysis revealed cortical malformations in 10 cases. Of the 10 patients with a postoperative follow-up of at least 12 months, 6 (60%) were seizure-free (Engel Class Ia), 2 (20%) experienced a significant reduction of seizures (Engel Class II), and 2 (20%) were unchanged (Engel Class IV).
The present study indicates that stereo-EEG plays a prominent role in the presurgical evaluation of focal epilepsies also in the first years of life and that it may offer a surgical option in particularly complex cases that would have scarcely benefitted from further medical treatment. Results of stereo-EEG–guided resective surgery were excellent, with 80% of patients exhibiting a substantial improvement in seizures. In consideration of the potentially life-threatening risks of major intracranial surgery in this specific age group, the authors recommend reserving stereo-EEG evaluations for infants with realistic chances of benefiting from surgery.
Anna Miserocchi, Beatrice Cascardo, Chiara Piroddi, Dalila Fuschillo, Francesco Cardinale, Lino Nobili, Stefano Francione, Giorgio Lo Russo and Massimo Cossu
The authors' goal in this paper was to retrospectively evaluate the relevance of the presurgical workup and the postoperative outcome in children (< 15 years) who undergo surgery for temporal lobe epilepsy (TLE).
The authors performed a retrospective analysis of 68 patients (43 boys and 25 girls) who underwent resection for TLE between 2001 and 2010 at a single center and had a minimum postoperative follow-up of 12 months. Presurgical investigations included full clinical evaluation, interictal electroencephalography (EEG), and MRI in all cases; cognitive evaluation in patients older than 5 years; scalp video-EEG in 46 patients; and invasive EEG in 3 patients. Clinical evaluation included a careful assessment of ictal semiology (based on anamnestic reports or video-EEG review), with particular attention to early signs and/or symptoms suggestive of temporal lobe origin of the seizure. Microsurgical resections were performed within the anatomical limits of the temporal lobe, and surgical specimens were processed for histological examination. Postoperative assessment of seizure outcome (Engel classification system) and cognitive performance was conducted at regular intervals. The effect on postoperative seizure outcome (good = Engel Class I; poor = Engel Classes II–IV) of several presurgical and surgical variables was investigated by bivariate statistical analysis.
All patients had at least 1 early sign or symptom suggesting a temporal lobe origin of their seizures. Lateralized interictal or ictal EEG abnormalities were seen in all patients, and they were localized to the temporal lobe in 45 patients. In all cases MRI demonstrated a structural abnormality. Surgery consisted of a tailored anterior temporal lobectomy in 64 patients and a neocortical lesionectomy in 4 patients. Postoperatively, 58 patients (85%) were in Engel Class I. Variables significantly associated with a poor outcome were preoperative sensory motor deficit (p = 0.019), mental retardation (p = 0.003), MRI abnormalities extending outside the temporal lobe (p = 0.0018), history of generalized seizures (p = 0.01) or status epilepticus (p = 0.008), unremarkable histology (p = 0.001), seizures immediately postoperatively (p = 0.00001), and ipsilateral epileptiform activity on postoperative EEG (p = 0.005). At postoperative neuropsychological assessment, the percentage of patients with a pathological score at the final visit invariably decreased compared with that at the preoperative evaluation in all considered cognitive domains.
Among the study population, a surgical selection based on a noninvasive evaluation was possible in most patients. The invaluable information resulting from the rigorous noninvasive electroclinical and neuroimaging evaluation can lead to excellent surgical results without the use of invasive, time-consuming, and expensive diagnostic tools. The potential reduction of invasiveness-related risks, complexity, and costs of presurgical investigations should hopefully allow for an increase in the number of children with TLE who will receive surgery, particularly in centers with limited technological resources.
Massimo Cossu, Francesco Cardinale, Nadia Colombo, Roberto Mai, Lino Nobili, Ivana Sartori and Giorgio Lo Russo
The authors report on indications for, techniques of, and results of stereoelectroencephalography (stereo-EEG) monitoring in the presurgical evaluation of childhood drug-resistant focal epilepsy.
Thirty-five children (24 boys and 11 girls; mean age 8.8 ± 3.9 years; mean age at seizure onset 2.1 ± 2.2 years) underwent 37 tailored stereotactic placements of intracerebral, multilead electrodes for intensive monitoring of seizures (stereo-EEG). Two children underwent exploration twice. Investigations prior to stereo-EEG monitoring, including magnetic resonance imaging and video-EEG of the scalp, revealed variable patterns of localizing incoherence among clinical, electrophysiological, and anatomical findings in all cases. A total of 426 electrodes were implanted (mean 11.5 ± 2.6 per procedure) according to individualized arrangements.
The stereo-EEG monitoring enabled recording of 826 seizures (mean 22 ± 45 per procedure) and mapping of critically functional areas. One untoward event consisted of intracranial breakage of an electrode. Resections of the epileptogenic zone were performed according to results of stereo-EEG recordings. They consisted of cortical removal in seven cases, removal of the lesion and epileptogenic cortex in 26 cases, and lesion removal in two cases. Transient postoperative neurological deficits were observed in 13 patients, and permanent anticipated visual field defects occurred in seven patients. According to the Engel postoperative classification of seizure outcome, 60% of cases were in Class I, 74% had significant improvement (Classes I–III), and 26% were unchanged (mean follow up 31.9 ± 20.6 months).
Stereoelectroencephalography monitoring is a helpful and well-tolerated technique for the definition of the epileptogenic zone in complex cases of childhood drug-resistant epilepsy. It provides essential information for safe resections that should result in excellent outcomes in a considerable number of patients.
Francesco Cardinale, Michele Rizzi, Piergiorgio d’Orio, Giuseppe Casaceli, Gabriele Arnulfo, Massimo Narizzano, Davide Scorza, Elena De Momi, Michele Nichelatti, Daniela Redaelli, Maurizio Sberna, Alessio Moscato and Laura Castana
The purpose of this study was to compare the accuracy of Neurolocate frameless registration system and frame-based registration for robotic stereoelectroencephalography (SEEG).
The authors performed a 40-trajectory phantom laboratory study and a 127-trajectory retrospective analysis of a surgical series. The laboratory study was aimed at testing the noninferiority of the Neurolocate system. The analysis of the surgical series compared Neurolocate-based SEEG implantations with a frame-based historical control group.
The mean localization errors (LE) ± standard deviations (SD) for Neurolocate-based and frame-based trajectories were 0.67 ± 0.29 mm and 0.76 ± 0.34 mm, respectively, in the phantom study (p = 0.35). The median entry point LE was 0.59 mm (interquartile range [IQR] 0.25–0.88 mm) for Neurolocate-registration–based trajectories and 0.78 mm (IQR 0.49–1.08 mm) for frame-registration–based trajectories (p = 0.00002) in the clinical study. The median target point LE was 1.49 mm (IQR 1.06–2.4 mm) for Neurolocate-registration–based trajectories and 1.77 mm (IQR 1.25–2.5 mm) for frame-registration–based trajectories in the clinical study. All the surgical procedures were successful and uneventful.
The results of the phantom study demonstrate the noninferiority of Neurolocate frameless registration. The results of the retrospective surgical series analysis suggest that Neurolocate-based procedures can be more accurate than the frame-based ones. The safety profile of Neurolocate-based registration should be similar to that of frame-based registration. The Neurolocate system is comfortable, noninvasive, easy to use, and potentially faster than other registration devices.
Massimo Cossu, Dalila Fuschillo, Giuseppe Casaceli, Veronica Pelliccia, Laura Castana, Roberto Mai, Stefano Francione, Ivana Sartori, Francesca Gozzo, Lino Nobili, Laura Tassi, Francesco Cardinale and Giorgio Lo Russo
Radiofrequency thermocoagulation (RF-TC) of presumed epileptogenic lesions and/or structures has gained new popularity as a treatment option for drug-resistant focal epilepsy, mainly in patients with mesial temporal lobe epilepsy. The role of this minimally invasive procedure in more complex cases of drug-resistant epilepsy, which may require intracranial electroencephalographic evaluation, has not been fully assessed. This retrospective study reports on a case series of patients with particularly complex focal epilepsy who underwent stereoelectroencephalography (SEEG) evaluation with stereotactically implanted multicontact intracerebral electrodes for the detailed identification of the epileptogenic zone (EZ) and who received RF-TC in their supposed EZ (according to SEEG findings).
Eighty-nine patients (49 male and 40 female; age range 2–49 years) who underwent SEEG evaluation and subsequent RF-TC of the presumed EZ at the authors' institution between January 2008 and December 2013 were selected. Brain MRI revealed structural abnormalities in 43 cases and no lesions in 46 cases. After SEEG, 67 patients were judged suitable for resective surgery (Group 1), whereas surgery was excluded for 22 patients (Group 2). Thermocoagulation was performed in each of these patients by using the previously implanted multicontact recording electrodes and delivering RF-generated currents to adjacent electrode contacts.
The mean number of TC sites per patient was 10.6 ± 7.2 (range 1–33). Sustained seizure freedom occurred after TC in 16 patients (18.0%) (13 in Group 1 and 3 in Group 2). A sustained worthwhile improvement was reported by 9 additional patients (10.1%) (3 in Group 1 and 6 in Group 2). As a whole, 25 patients (28.1%) exhibited a persistent significant improvement in their seizures. More favorable results were observed in patients with nodular heterotopy (p = 0.0001389), those with a lesion found on MRI (not significant), and those with hippocampal sclerosis (not significant). Other variables significantly correlated to seizure freedom were the patient's age (p = 0.02885) and number of intralesional TC sites (p = 0.0271). The patients in Group 1 who did not benefit at all (21 patients) or who experienced only a transient benefit (30 patients) from TC underwent microsurgical resection of their EZ. Thermocoagulation was followed by severe permanent neurological deficits in 2 patients (an unexpected complex neuropsychological syndrome in one patient and an expected and anticipated permanent motor deficit in the other).
This study provides evidence that SEEG-guided TC in the EZ may be a treatment option for particularly complex drug-resistant focal epilepsy that requires invasive evaluation. A small subset of patients who achieve seizure freedom or worthwhile improvement may avoid open surgery or take advantage of an otherwise unexpected treatment if resection is not an option. Patients with epileptogenic nodular heterotopy are probably ideal candidates for this treatment.
Michele Rizzi, Martina Revay, Piergiorgio d’Orio, Pina Scarpa, Valeria Mariani, Veronica Pelliccia, Martina Della Costanza, Matteo Zaniboni, Laura Castana, Francesco Cardinale, Giorgio Lo Russo and Massimo Cossu
Surgical treatment of drug-resistant epilepsy originating from the posterior quadrant (PQ) of the brain often requires large multilobar resections, and disconnective techniques have been advocated to limit the risks associated with extensive tissue removal. Few previous studies have described a tailored temporoparietooccipital (TPO) disconnective approach; only small series with short postoperative follow-ups have been reported. The aim of the present study was to present a tailored approach to multilobar PQ disconnections (MPQDs) for epilepsy and to provide details about selection of patients, presurgical investigations, surgical technique, treatment safety profile, and seizure and cognitive outcome in a large, single-center series of patients with a long-term follow-up.
In this retrospective longitudinal study, the authors searched their prospectively collected database for patients who underwent MPQD for drug-resistant epilepsy in the period of 2005–2017. Tailored MPQDs were a posteriori grouped as follows: type I (classic full TPO disconnection), type II (partial TPO disconnection), type III (full temporooccipital [TO] disconnection), and type IV (partial TO disconnection), according to the disconnection plane in the occipitoparietal area. A bivariate statistical analysis was carried out to identify possible predictors of seizure outcome (Engel class I vs classes II–IV) among several presurgical, surgical, and postsurgical variables. Preoperative and postoperative cognitive profiles were also collected and evaluated.
Forty-two consecutive patients (29 males, 24 children) met the inclusion criteria. According to the presurgical evaluation (including stereo-electroencephalography in 13 cases), 12 (28.6%), 24 (57.1%), 2 (4.8%), and 4 (9.5%) patients received a type I, II, III, or IV MPQD, respectively. After a mean follow-up of 80.6 months, 76.2% patients were in Engel class I at last contact; at 6 months and 2 and 5 years postoperatively, Engel class I was recorded in 80.9%, 74.5%, and 73.5% of cases, respectively. Factors significantly associated with seizure freedom were the occipital pattern of seizure semiology and the absence of bilateral interictal epileptiform abnormalities at the EEG (p = 0.02). Severe complications occurred in 4.8% of the patients. The available neuropsychological data revealed postsurgical improvement in verbal domains, whereas nonunivocal outcomes were recorded in the other functions.
The presented data indicate that the use of careful anatomo-electro-clinical criteria in the presurgical evaluation allows for customizing the extent of surgical disconnections in PQ epilepsies, with excellent results on seizures and an acceptable safety profile.