Independent component analysis: a reliable alternative to general linear model for task-based fMRI.

Background: Functional magnetic resonance imaging (fMRI) is a valuable tool for the presurgical evaluation of patients undergoing neurosurgeries. Although many pre-processing steps have been modified according to advances in recent years, statistical analysis has remained largely the same since the first days of fMRI. In this study, we examined the ability of Independent Component Analysis (ICA) to separate the activation of a language task in fMRI, and we compared it with the results of the General Lineal Model (GLM). Methods: Sixty patients undergoing evaluation for brain surgery due to various brain lesions and/or epilepsy and 20 control subjects completed an fMRI language mapping protocol that included three tasks, resulting in 259 fMRI scans. Depending on brain lesion characteristics, patients were allocated to (1) static/chronic not-expanding lesions (Group 1) and (2) progressive/expanding lesions (Group 2). GLM and ICA statistical maps were evaluated by fMRI experts to assess the performance of each technique. Results: In the control group, ICA and GLM maps were similar without any superiority of either technique. In Group 1 and Group 2, ICA performed statistically better than GLM, with a p-value of < 0.01801 and < 0.0237, respectively. This indicated that ICA performs as well as GLM when the subjects are able to cooperate well (less movement, good task performance), but ICA could outperform GLM in the patient groups. When both techniques were combined, 240 out of 259 scans produced reliable results, showing that the sensitivity of task-based fMRI can be increased when both techniques are integrated with the clinical setup. Conclusion: ICA may be slightly more advantageous, compared to GLM, in patients with brain lesions, across the range of pathologies included in our population and independent of symptoms chronicity. Our findings suggest that GLM analysis may be more susceptible to brain activity perturbations induced by a variety of lesions or scanner-induced artifacts due to motion or other factors. In our research, we demonstrated that ICA is able to provide fMRI results that can be used in surgery, taking into account patient and task-wise aspects that differ from those when fMRI is used in research.

Frontal lobe epilepsy and mild malformation with oligodendroglial hyperplasia: Further observations on electroclinical and imaging phenotypes, and surgical perspectives.

OBJECTIVE: Mild malformation with oligodendroglial hyperplasia (MOGHE) is a recently described clinicopathologic entity, associated with drug-resistant epilepsy and extensive epileptogenic networks. Knowledge is accumulating about particular electroclinical phenotypes, correlations with imaging, and potential prognostic significance for surgical outcomes. The study adds relevant information by documenting the presence of a hyperkinetic frontal lobe seizure phenotype in adolescents and an epileptic encephalopathy phenotype in young children. METHODS: Five cases were subjected to a structured presurgical evaluation protocol, including EEG-FMRI, chronic and acute invasive EEG, subjected to frontal lobe surgery with postoperative follow-up between 15 months and 7 years. RESULTS: In the two adult cases, surface EEG demonstrated lateralized widespread frontal lobe epileptogenicity and hyperkinetic semiological features. MRI demonstrated cortical white matter blurring and deeper white matter abnormalities. EEG-FMRI suggested concordant frontal lobe involvement. iEEG demonstrated a widespread frontal lobe epilepsy network. The three young children demonstrated a diffuse epileptic encephalopathy phenotype, with nonlocalizing, nonlateralizing surface EEG, and "spasms" as the main seizure type. MRI demonstrated extensive frontal lobe subcortical gray and white matter abnormalities, consistent with MOGHE literature for this age, while EEG-FMRI, in 2/3, demonstrated concordant frontal lobe involvement. They did not undergo chronic iEEG, and the resection was assisted by acute intraoperative ECoG. All cases were subjected to extensive frontal lobectomies with Engel class IA (2/5), IB (1/5), and IIB (2/5) outcomes. SIGNIFICANCE: The study confirms the presence of frontal lobe epilepsy and epileptic encephalopathy phenotypes, in accordance with epilepsy phenotypes already described in MOGHE literature. Presurgical evaluation studies, including EEG-FMRI, can provide strong lateralizing and localizing evidence of the epileptogenic networks involved. All responded favorably to extensive frontal lobe resections, despite widespread epileptic activity recorded by surface and intracranial EEG pre- and postoperatively; an epileptic encephalopathy phenotype, in the first years of life, should not discourage such a resection.

Temporal lobe "plus" epilepsy associated with oligodendroglial hyperplasia (MOGHE).

BACKGROUND: Mild malformation of cortical dysplasia (mMCD) with oligodendroglial hyperplasia (MOGHE) is an epilepsy-related pathologic entity highlighted in post-surgical specimens of frontal lobe epilepsy (FLE) patients. AIMS OF THE STUDY: We present two temporal lobe epilepsy (TLE) cases with MOGHE and discuss clinical, neurophysiological, and neuroimaging features that may be indicative of surgical outcome. METHODS: We identified two cases with MOGHE out of 30 temporal lobe epilepsy (TLE) surgical patient cohort, whose pathological distribution spared the hippocampal structures. RESULTS: The TLE cases shared common features with the FLE series in terms of patient profiles, MRI findings and post-surgical outcome. TLE plus seizure semiology combined with extratemporal scalp electroencephalographic (EEG) and electrocorticographic (ECoG) epileptiform elements at a distance from the imaging lesion were suggestive of an underlying multifocal pathology. CONCLUSIONS: MOGHE pathology has to be considered in the decision-making process for TLE epilepsy surgery when this constellation of features is met.

Incidence, time trends and survival patterns of childhood pilocytic astrocytomas in Southern-Eastern Europe and SEER, US.

Pilocytic astrocytomas (PA) comprise the most common childhood central nervous system (CNS) tumor. Exploiting registry-based data from Southern and Eastern Europe (SEE) and SEER, US, we opted to examine incidence, time trends, survival and tentative outcome disparities of childhood PA by sociodemographic and clinical features. Childhood PA were retrieved from 12 SEE registries (N = 552; 1983-2014) and SEER (N = 2723; 1973-2012). Age-standardized incidence rates (ASR) were estimated and survival was examined via Kaplan-Meier and Cox regression analysis. ASR of childhood PA during 1990-2012 in SEE was 4.2/106, doubling in the USA (8.2/106). Increasing trends, more prominent during earlier registration years, were recorded in both areas (SEE: +4.1 %, USA: +4.6 %, annually). Cerebellum comprised the most common location, apart from infants in whom supratentorial locations prevailed. Age at diagnosis was 1 year earlier in SEE, whereas 10-year survival was 87 % in SEE and 96 % in SEER, improving over time. Significant outcome predictors were age <1 year at diagnosis diagnosis (hazard ratio, HR [95% confidence intervals]: 3.96, [2.28-6.90]), female gender (HR: 1.38, [1.01-1.88]), residence in SEE (HR: 4.07, [2.95-5.61]) and rural areas (HR: 2.23, [1.53-3.27]), whereas non-cerebellar locations were associated with a 9- to 12-fold increase in risk of death. The first comprehensive overview of childhood PA epidemiology showed survival gains but also outcome discrepancies by geographical region and urbanization pointing to healthcare inequalities. The worse prognosis of infants and, possibly, females merits further consideration, as it might point to treatment adjustment needs, whereas expansion of systematic registration will allow interpretation of incidence variations.

Childhood central nervous system tumour mortality and survival in Southern and Eastern Europe (1983-2014): Gaps persist across 14 cancer registries.

AIM: Childhood central nervous system (CNS) tumour registration and control programs in Southern and Eastern Europe remain thin, despite the lethal nature of the disease. Mortality/survival data were assembled to estimate the burden of malignant CNS tumours, as well as the potential role of sociodemographic survival determinants across 14 cancer registries of this region. METHODS: Average age-adjusted mortality rates were calculated, whereas time trends were quantified through Poisson and Joinpoint regressions. Kaplan-Meier curves were derived for the maximum and the more recent (10 and 5 year) registration periods. Multivariate Cox regression models were used to assess demographic and disease-related determinants. RESULTS: Variations in mortality (8-16 per million) and survival (5-year: 35-69%) were substantial among the participating registries; in most registries mortality trend was stable, whereas Bulgaria, having the highest starting rate, experienced decreasing annual mortality (-2.4%, p=0.001). A steep decrease in survival rates was evident before the second year of follow-up. After controlling for diagnostic subgroup, age, gender and diagnostic year, Greece seemed to present higher survival compared with the other contributing registries, although the follow-up period was short. Irrespective of country, however, rural residence was found to impose substantial adverse repercussions on survival (hazard ratio (HR): 1.2, 95% confidence interval (CI): 1.1-1.4). CONCLUSION: Cross-country mortality and survival variations possibly reflect suboptimal levels of health care delivery and cancer control in some regions of Southern and Eastern Europe, notwithstanding questionable death certification patterns or follow-up procedures. Continuous childhood cancer registration and linkage with clinical data are prerequisite for the reduction of survival inequalities across Europe.

Childhood central nervous system tumours: Incidence and time trends in 13 Southern and Eastern European cancer registries.

AIM: Following completion of the first 5-year nationwide childhood (0-14 years) registration in Greece, central nervous system (CNS) tumour incidence rates are compared with those of 12 registries operating in 10 Southern-Eastern European countries. METHODS: All CNS tumours, as defined by the International Classification of Childhood Cancer (ICCC-3) and registered in any period between 1983 and 2014 were collected from the collaborating cancer registries. Data were evaluated using standard International Agency for Research on Cancer (IARC) criteria. Crude and age-adjusted incidence rates (AIR) by age/gender/diagnostic subgroup were calculated, whereas time trends were assessed through Poisson and Joinpoint regression models. RESULTS: 6062 CNS tumours were retrieved with non-malignant CNS tumours recorded in eight registries; therefore, the analyses were performed on 5191 malignant tumours. Proportion of death certificate only cases was low and morphologic verification overall high; yet five registries presented >10% unspecified neoplasms. The male/female ratio was 1.3 and incidence decreased gradually with age, apart from Turkey and Ukraine. Overall AIR for malignant tumours was 23/10(6) children, with the highest rates noted in Croatia and Serbia. A statistically significant AIR increase was noted in Bulgaria, whereas significant decreases were noted in Belarus, Croatia, Cyprus and Serbia. Although astrocytomas were overall the most common subgroup (30%) followed by embryonal tumours (26%), the latter was the predominant subgroup in six registries. CONCLUSION: Childhood cancer registration is expanding in Southern-Eastern Europe. The heterogeneity in registration practices and incidence patterns of CNS tumours necessitates further investigation aiming to provide clues in aetiology and direct investments into surveillance and early tumour detection.

EEG-fMRI findings in late seizure recurrence following temporal lobectomy: A possible contribution of area tempestas.

Late seizure relapses following temporal lobectomy for drug-resistant temporal lobe epilepsy occur in 18-30% of operated-on cases, and recent evidence suggests that a significant proportion of them are due to maturation and activation of proepileptic tissue having defied initial resection and located at the vicinity of or at a short distance from its borders, usually over the posterior medial, basal temporal-occipital, and lateral temporal regions. Experimental studies in animals and functional imaging studies in humans suggest that the area tempestas, a particular region of the basal-frontal piriform cortex, is critical for kindling and initiation and propagation of seizure activity arising from different cortical foci, especially limbic ones. This case report of a patient with late seizure relapse, three years following an initially successful right temporal lobectomy for ipsilateral medial temporal sclerosis, is the first one in the literature to demonstrate interictal EEG-fMRI evidence of significant BOLD signal changes over the inferior, basal and lateral temporal and temporooccipital cortices posterior to the resection margin, plus a significant BOLD signal change over the ipsilateral basal frontal region, closely corresponding to the piriform cortex/area tempestas. Our case study provides further functional imaging evidence in support of maturation/activation of proepileptic tissue located at the vicinity of the initial temporal lobe resection in cases of late seizure relapses and suggests, in addition, a possible role for the piriform cortex/area tempestas in the relapsing process.

Surgical outcome in neocortical resections of type IIId focal cortical dysplasia with accompanying medial temporal pathology.

Focal cortical dysplasia (FCD) type IIId is a newly proposed type associated with early-life brain insults. Such patients are often considered unsuitable for resective epilepsy surgery, given the usually wide extent of the lesion and the poor correlation of MRI to the epileptogenic pathology. Two patients with intractable epilepsy, early-life ischemic/traumatic injury and MRI findings of extensive unilateral cystic-gliotic and ipsilateral medial temporal sclerotic-malformative lesions were subjected to presurgical evaluation revealing well-localized neocortical ictal onsets. They underwent tailored neocortical resections sparing medial temporal areas and achieved Engel class I postsurgical outcomes. Histopathology was consistent with type IIId focal cortical dysplasia. Successful outcomes with tailored resections may be achieved in cases with this subtype of focal cortical dysplasia, in the presence of converging and well-localized semiological, EEG and functional imaging data, even on a background of complex and extensive MRI abnormalities. Medial temporal pathology, although often present in this setting, is not necessarily the site of ictal onsets, and its resection may not be always mandatory for a favorable outcome.

Extratemporal surface EEG features do not preclude successful surgical outcomes in drug-resistant epilepsy patients with unitemporal MRI lesions.

Of 47 patients with onset of intractable partial seizures and temporal lobe MRI lesions, subjected to presurgical evaluation and temporal lobe surgery, we identified eight (mean age: 24 years; range: 7-52 years) demonstrating surface interictal and/or ictal EEG features suggestive of an extratemporal localisation. All eight patients underwent surgery aiming to predominantly resect the lesion, without extending to the extratemporal region. The patients were prospectively followed (mean follow-up duration: 38 months; range: 12-66 months) and all achieved excellent postoperative seizure control. Extratemporal surface interictal/ictal EEG features were more often encountered in tumoural and focal cortical dysplasia cases, compared with medial temporal sclerosis cases, and were most frequently localised over frontopolar and suprasylvian-pericentral locations. We postulate that propagation of interictal/ictal activity from the epileptogenic region of the temporal lobe to extratemporal neocortical areas, perhaps utilising the temporal pole and insula as intermediary nodes of a common epileptogenic network, accounts for the presence of our cohort's discordant lesion and EEG features.

Epileptogenic networks in two patients with hypothalamic hamartoma.

Hypothalamic hamartomas (HH) are typically associated with gelastic seizures but also implicated in the genesis of other seizure types. In order to identify networks involved in seizure generation, we performed EEG-fMRI in two adult patients with HH, the first with predominantly gelastic seizures and the second with complex partial and no typical gelastic seizures. The ictal and interictal analysis of the patient with gelastic seizures revealed the involvement of the HH, the cingulate gyrus, the precuneus and the prefrontal cortex. The interictal analysis of the patient with complex partial seizures, showed changes in blood oxygen-level dependent signal over the temporal lobes, the base of the frontal lobe, the cingulate, the precuneus and the prefrontal cortex, but not the HH. The differences in the neural networks implicated may account for differences in clinical manifestation of seizures owing to HH.

Hemispherotomy or lobectomy? The role of presurgical neuroimaging in a young case of a large porencephalic cyst with intractable epilepsy.

A young patient with a large left hemisphere porencephalic cyst underwent neuroimaging investigation (functional magnetic resonance imaging (fMRI), EEG-fMRI, DTI tractography) during presurgical evaluation for intractable epilepsy. The functional workup showed that (a) the healthy hemisphere had undertaken language processing, primary and secondary sensory functions of bilateral upper and lower extremities, and bilateral feet motion, and (b) the porencephalic hemisphere had retained contralateral arm and shoulder motion. EEG-fMRI localized the epileptogenic area occipitally. Tractography anatomically supported the above. Neuroimaging tailored surgery into selective lobectomy, thereby preserving all sensorimotor functionality and strongly supporting its use for presurgical evaluation of patients with large hemispheric lesions.

Limited resection of focal cortical dysplasia and associated epileptogenic cortex may lead to positive surgical outcome.

A drug-resistant epilepsy patient with premotor type IIb focal cortical dysplasia is described with a positive postoperative outcome following partial resection of the lesion and epileptogenic zone. Presurgical fMRI of the sensorimotor areas showed haemodynamic responses over the posterior border of the lesion and ictal EEG-fMRI revealed activation of both the primary sensorimotor strip and premotor lesion area. Almost continuous 1-2 Hz interictal spiking was recorded during a chronic ECoG study over the primary sensorimotor cortex. Following partial resection of the lesion, an acute ECoG revealed marked reduction of epileptic activity over the sensorimotor area. Post-operatively, seizure control was significantly improved (class IV ILAE outcome). Although partial FCD resections predict a worse postoperative outcome, individual patients may still respond favourably. The type of lesion, resected portion, and histopathology may be included among factors related to successful outcome.

Five-aminolevulinic acid for fluorescence-guided resection of recurrent malignant gliomas: a phase ii study.

OBJECTIVE: To assess the feasibility of 5-aminolevulinic acid (5-ALA) fluorescence guidance for resection of recurrent malignant brain tumors. METHODS: In a multicenter prospective, single-arm, uncontrolled phase II study, 36 patients with recurrent glioma (World Health Organization grade III/IV) received 5-ALA before surgery. After microsurgical resection, biopsies from pathological and nonpathological areas (as identified under conventional white light) were obtained to determine the positive predictive value (PPV) of 5-ALA-induced tissue fluorescence in detecting tumors. Adverse events, neurological examinations, and survival data were documented for a minimal follow-up of 6 months. RESULTS: The patient-based PPV, defined as the percentage of patients showing positive tumor cell identification in all biopsies taken from areas of weak and strong fluorescence was 97.2% for pathological areas and 79.4% in nonpathological areas. Within areas of strong fluorescence, PPV was higher (91.7%) compared with that of weak fluorescence (82.4%). On the biopsy level for nonpathological-appearing tissue under white light (157 biopsies), the PPV of tissue fluorescence was 93.0% compared with 99.5% in pathological-appearing tissue (197 biopsies). Again, within areas of strong fluorescence, PPV was higher (96.9%) compared with that of weak fluorescence (90.3%). There were no adverse events pertaining to the study drug. CONCLUSION: 5-ALA fluorescence has a high predictive value for the detection of tumor in recurrent gliomas. Prior treatment modalities, such as radiation or chemotherapy, do not invalidate the fluorescence guidance with 5-ALA. 5-ALA fluorescence guidance is an effective surgical adjunct in the surgery of recurrent malignant gliomas.

Demyelinating plaque imitates an intramedullary tumour.

An isolated spinal demyelinating lesion is very rare and almost always associated with multiple sclerosis. There are only a few reports of biopsy or resection of MS-associated lesions. Sometimes the radiological and the histopathological findings can lead to a false diagnosis of a tumour. A 15-year-old girl presented with a progressive spastic tetraparesis and various associated clinical symptoms. Magnetic resonance imaging (MRI) suggested a possible intramedullary tumour extending from C4 to C7 and the need for surgical intervention. There was no previous neurological or other history and the brain MRI was normal. The performing surgeons based their procedures on oncological criteria. The extracted lesion was finally diagnosed as a demyelinating plaque. The postoperative course was uneventful without deterioration of the neurological status and the young patient improved completely after 4-months of rehabilitation. After an 8-year follow-up, the patient remains in remission and free of neurological defects. Apart from the radiological findings, the CSF exam as well as the evoked potentials does not suggest a diagnosis of MS. A demyelinating plaque in the cervical spinal cord can occasionally imitate a cervical intramedullary tumour leading to an operation. Such lesions underscore the sensitivity of present-day lesion detection procedures. An addition of a MS work up could be beneficial in some cases of intramedullary tumours without a typical history, although in the case presented this type of workup was negative.