Surgery for Intractable Infantile Spasms: Neuroimaging Perspectives

Summary: Twenty-three infants and children underwent cortical resection ( n = 15) or hemispherectomy (n = 8) for intractable infantile spasms. Infantile spasms were present at the time of surgery in 17 of the 23 patients; in six, spasms had evolved to other seizure types during surgical evaluation. Children with a remote history of infantile spasms were excluded from this study. Focal or hemispheric lesions were identified by magnetic resonance imaging in seven children; an additional two showed focal atrophy without a discrete lesion. Positron emission tomography (PET) showed lateralized or localized abnormalities of cerebral glucose utilization in all patients; in 14, PET was the only neuroimaging modality to identify the epileptogenic cortex. When this occurred, neuropathological examination of resected brain tissue typically showed malformative and dysplastic cortical lesions. Focal interictal and/or ictal electrographic abnormalities were present in all patients, and corresponded well with localization from neuroimaging. None of the patients were subjected to chronic invasive electrographic monitoring with intracranial electrodes. At follow-up (range 4–67 months; mean 28.3 months), 15 children were seizure-free, three had 90% seizure control, one had 75% seizure control, and four failed to benefit from surgery with respect to seizure frequency.     

Intrinsic epileptogenicity of human dysplastic cortex as suggested by corticography and surgical results

Cortical dysplastic lesions (CDyLs) are often associated with severe partial epilepsies. We describe the electrographic counterpart of this high degree of epileptogenicity, manifested by continuous or frequent rhythmic epileptogenic discharges recorded directly from CDyLs during intraoperative electrocorticography (ECoG). These ictal or continuous epileptogenic discharges (I/CEDs) assumed one of the following three patterns: (1) repetitive electrographic seizures, (2) repetitive bursting discharges, or (3) continuous or quasicontinuous rhythmic spiking. One or more of these patterns were present in 23 of 34 patients (67%) with intractable partial epilepsy associated with CDyLs, and in only 1 of 40 patients (2.5%) with intractable partial epilepsy associated with other types of structural lesions. I/CEDs were usually spatially restricted, thus contrasting with the more widespread interictal ECoG epileptic activity, and tended to colocalize with the magnetic resonance imaging–defined lesion. Completeness of excision of cortical tissue displaying I/CEDs correlated positively with surgical outcome in patients with medically intractable seizures; i.e., three-fourths of the patients in whom it was entirely excised had favorble surgical outcome; in contrast, uniformly poor outcome was observed in those patients in whom areas containing I/CEDs remained in situ. We conclude that CDyLs are highly and intrinsically epileptogenic, and that intraoperative ECoG identification of this intrinsically epileptogenic dysplastic cortical tissue is crucial to decide the extent of excision for best seizure control.     

Ictal SPECT is useful in localizing the epileptogenic zone in infants with cortical dysplasia

Aims. To assess the localizing value of ictal SPECT in very young epilepsy surgery candidates when cerebral haemodynamic responses are known to be immature. Methods. We retrospectively studied 13 infants with intractable focal epilepsy caused by focal cortical dysplasia (FCD). Completeness of resection of the (1) ictal SPECT hyperperfusion zone and (2) cerebral cortex with prominent ictal and interictal abnormalities on intracranial EEG (ECoG or long‐term invasive monitoring) and the MRI lesion, when present, were correlated with postoperative seizure outcome. Results. All five patients with complete resection of the ictal SPECT hyperperfusion zone were seizure‐free compared to only one of eight patients with incomplete or no excision of hyperperfusion zones (p=0.00843). Similar results were noted for the MRI/iEEG‐defined epileptogenic region; five of six patients with complete removal were seizure‐free, whereas only one of seven incompletely resected patients was seizure‐free (p=0.02914). All four patients who underwent complete resection of both regions were seizure‐free compared to none of the six with incomplete resection (p=0.01179). Conclusion. Despite age‐related differences in cerebral perfusion, ictal SPECT provides useful localization data in infants with FCD. Complete resection of the hyperperfused regions is a strong predictor of favourable outcome. The added information may alleviate the need for invasive EEG evaluations in some patients.     

Subdural EEG patterns in children with taylor-type cortical dysplasia: comparison with nondysplastic lesions.

The authors compared interictal and ictal abnormalities from chronic intracranial recordings in children with Taylor-type cortical dysplasia (TTCD) and nondysplastic lesions. Interictal epileptiform discharges and ictal patterns were retrospectively analyzed in 13 children with TTCD and 12 children with nondysplastic lesions (tumor, 4; gliosis, 8). Features analyzed and compared between groups included the morphologic and temporal characteristics and field distribution of ictal and interictal patterns and rapidity of ictal propagation. The frequency of runs of interictal continuous epileptiform discharges (CEDs) or bursts of fast activity did not differ significantly between dysplastic and nondysplastic tissue. Fast frequencies characterized the majority of seizure onsets (49/67) in dysplastic patients and repetitive spikes were more frequent at seizure onset (31/56) in nondysplastic patients (P < 0.002). Field of ictal onset was limited to adjacent cortex and independent of histology. The interval between seizure onset and spread to adjacent or nonadjacent cortex was significantly shorter in dysplastic than nondysplastic patients. Interictal EEG patterns are not specific markers of dysplastic cortex but the morphology of ictal onset differs significantly with dysplastic cortex showing significantly more rapid propagation than nondysplastic cortex. These findings suggest that markers other than CEDs physiologically characterize dysplastic cortex and that children with TTCD exhibit more widespread excitability of neural pathways.     

Intraictal Activation in the Neocortex: A Marker of the Epileptogenic Region

Summary: During the course of a seizure, subdural recordings often show secondary areas which develop in-dependent electrographic sequences that may outlast the primary seizure sequence. We reviewed the subdural data on 8 patients with intraictal secondarily activated foci (ISF). In 6 patients, ISFs were documented to be capable of generating independent seizures; ISF seizures occurred during the initial subdural monitoring period in 3, but became ictal generators only after excision of the primary focus in the other 3. Prominent interictal abnormalities were observed at the ISFs in 5 of 8 patients. The ISF in 1 patient correlated with the structural lesion on magnetic resonance imaging (MRI) scan. We believe that ISFs have significant epileptogenicity and should be re-sected when possible.     

"Supplementary motor area (SMA) seizure" rather than "SMA epilepsy" in optimal surgical candidates: a document of subdural mapping

PURPOSE: To clarify the relationship between epileptogenic zone and supplementary motor area (SMA) in patients who were regarded as the optimal surgical candidates for their intractable SMA seizures. METHODS: We analyzed the epileptogenic zone at/or adjacent to the SMA in four patients with clinical SMA seizures. All four patients had noninvasive presurgical evaluations (long-term video/EEG monitoring, MRI, and neuroimaging with radioisotopes), which provided convergent results between ictal semiology and the epileptogenic area, and thus, they had chronically implanted subdural electrodes, and finally had focus resection with a follow-up period of more than 2 years. RESULTS: Three patients had lesions shown by MRI outside the SMA, and one patient had a lesion within the SMA. Interictal epileptiform discharges were seen at/or outside the SMA. Ictal EEG pattern originated from the SMA in one patient, from the high lateral frontal area in two patients, and from the precuneus in one patient. In the latter three patients, the ictal EEG pattern immediately spread to the SMA. Those ictal onset zones were consistently localized within/or just adjacent to the lesions revealed by MRI. Only one patient had SMA resection, and three had the resection of epileptogenic zone by preserving the SMA. No neurological deficits developed and good seizure control was achieved. CONCLUSION: Among surgical candidates for intractable SMA seizures, frontal cortex other than SMA or even parietal cortex can be epileptogenic, and thus, the SMA itself may not necessarily have to be resected. This notion is clinically important when selecting surgical candidates as well as when planning presurgical invasive evaluation in patients with intractable SMA seizures.     

Intractable Epilepsy and Structural Lesions of the Brain: Mapping, Resection Strategies, and Seizure Outcome

Forty-seven patients with structural brain lesions on neuroimaging studies and partial epilepsy intractable to medical therapy were studied. Prolonged noninvasive interictal and ictal EEG recording was performed, followed by more focused mapping using chronically implanted subdural electrode plates. Surgical procedures included lesion biopsy, maximal lesion excision, and/or resection of zones of epileptogenesis depending on accessibility and involvement of speech or other functional areas. The epileptogenic zone involved exclusively the region adjacent to the structural lesion in 11 patients. It extended beyond the lesion in 18 patients. Eighteen other patients had remote noncontiguous zones of epileptogenesis. Postoperative control of epilepsy was accomplished in 17 of 18 patients (94%) with complete lesion excision regardless of extent of seizure focus excision. Postoperative control of epilepsy was accomplished in 5 of 6 patients (83%) with incomplete lesion excision but complete seizure focus excision and in 12 of 23 patients (52%) with incomplete lesion excision and incomplete focus excision. The extent of lesion resection was strongly associated with surgical outcome either in itself (p less than 0.003), or in combination with focus excision. Focus resection was marginally associated with surgical outcome as a dichotomous variable (p = 0.048) and showed a trend toward significance (p = 0.07) only as a three-level outcome variable. We conclude that structural lesions are associated with zones of epileptogenesis in neighboring and remote areas of the brain. Maximum resection of the lesion offers the best chance at controlling intractable epilepsy; however, seizure control is achieved in many patients by carefully planned subtotal resection of lesions or foci.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hippocampal or neocortical lesions on magnetic resonance imaging do not necessarily indicate site of ictal onsets in partial epilepsy

Advances in neuroimaging techniques, particularly high-resolution magnetic resonance imaging (MRI), have proved invaluable in identifying structural brain lesions in patients with epilepsy. The assumption that such focal lesions invariably predict the site of seizure origin may not be correct, however. We report a series of 20 adults with medically intractable partial epilepsy, where high-resolution brain MRI disclosed a unilateral, focal, hippocampal, or neocortical lesion as the only abnormality in each case; nevertheless, based on electroencephalographic (EEG) recordings, ictal onsets arose from a completely different location than that of the MRI lesion. All patients underwent epilepsy surgery, with the operations based on ictal EEG findings, and all were followed at least 2 years after the resection. After the most recent follow-up examination, 50% (10/20) of the patients were completely seizure-free, 35% (7/20) had at least a 75% reduction in the number of seizures, and 15% (3/20) had less than a 75% reduction in the number of seizures. We conclude that the identification of a focal, structural, hippocampal, or neocortical lesion on brain MRI is not always indicative of the site of seizure origin in partial epilepsy. Furthermore, in cases of discordance between MRI and EEG data, a good outcome after epilepsy surgery is possible if EEG ictal onsets are definitive.     

False lateralization of electrographic onset in the setting of cerebral atrophy.

The localization of seizure onset relies on the concordance of clinical, electrographic, and imaging data, often supplemented by corroborating functional studies. On occasion, the presurgical evaluation may yield discordant information. Although the localization of seizure onset is sometimes in doubt, it is rare that the lateralization of the focus is in question. To date, there has been only a single publication on falsely lateralizing ictal EEG onsets in the setting of atrophic lesions. We describe two patients in whom the ictal EEG suggested seizure onset from the hemisphere opposite to the one with a sizeable atrophic lesion. The first patient was operated on without invasive EEG testing. In the second patient, we decided to place subdural electrodes before resection. In each case, resection of the lesion resulted in improvement of intractable seizures.     

Functional MRI characteristics of a focal region of cortical malformation not associated with seizure onset

Neuroimaging studies have demonstrated that heterotopic tissue of patients with "double cortex" is activated during motor and somatosensory tasks. Activation in patients with malformations of cortical development (MCD) has been variable, likely due to the heterogeneity of the disorder. We examined clinical, electroencephalography (EEG), neuropsychological, and functional MRI findings in a patient with intractable epilepsy secondary to MCD in the left temporal cortex. Invasive EEG monitoring revealed that the dysplastic tissue was not involved in ictal onset of seizures. Functional MRI tests of motion and object processing, memory encoding, and language demonstrated no activation within dysplastic tissue. Hemispheric asymmetries in activation for motion and object processing were evident, favoring the right hemisphere--a pattern not evident in controls. These weaker activations in the patient were present in tissue proximal to the seizure focus. Thus, nonepileptogenic dysplastic tissue may not support cognitive functions, with abnormal processing evident in epileptogenic tissue.