Initiating an epilepsy surgery program with limited resources in Indonesia.

To share the experiences of organizing the epilepsy surgery program in Indonesia. This study was divided into two periods based on the presurgical evaluation method: the first period (1999-2004), when interictal electroencephalogram (EEG) and magnetic resonance imaging (MRI) were used mainly for confirmation, and the second period (2005-2017), when long-term non-invasive and invasive video-EEG was involved in the evaluation. Long-term outcomes were recorded up to December 2019 based on the Engel scale. All 65 surgical recruits in the first period possessed temporal lobe epilepsy (TLE), while 524 patients were treated in the second period. In the first period, 76.8%, 16.1%, and 7.1% of patients with TLE achieved Classes I, II, and III, respectively, and in the second period, 89.4%, 5.5%, and 4.9% achieved Classes I, II, and III, respectively, alongside Class IV, at 0.3%. The overall median survival times for patients with focal impaired awareness seizures (FIAS), focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures were 9, 11 and 11 years (95% CI: 8.170-9.830, 10.170-11.830, and 7.265-14.735), respectively, with p = 0.04. The utilization of stringent and selective criteria to reserve surgeries is important for a successful epilepsy program with limited resources.

Cortico-striato-thalamo-cerebellar networks of structural covariance underlying different epilepsy syndromes associated with generalized tonic-clonic seizures.

Generalized tonic-clonic seizures (GTCS) are the severest and most remarkable clinical expressions of human epilepsy. Cortical, subcortical, and cerebellar structures, organized with different network patterns, underlying the pathophysiological substrates of genetic associated epilepsy with GTCS (GE-GTCS) and focal epilepsy associated with focal to bilateral tonic-clonic seizure (FE-FBTS). Structural covariance analysis can delineate the features of epilepsy network related with long-term effects from seizure. Morphometric MRI data of 111 patients with GE-GTCS, 111 patients with FE-FBTS and 111 healthy controls were studied. Cortico-striato-thalao-cerebellar networks of structural covariance within the gray matter were constructed using a Winner-take-all strategy with five cortical parcellations. Comparisons of structural covariance networks were conducted using permutation tests, and module effects of disease duration on networks were conducted using GLM model. Both patient groups showed increased connectivity of structural covariance relative to controls, mainly within the striatum and thalamus, and mostly correlated with the frontal, motor, and somatosensory cortices. Connectivity changes increased as a function of epilepsy durations. FE-FBTS showed more intensive and extensive gray matter changes with volumetric loss and connectivity increment than GE-GTCS. Our findings implicated cortico-striato-thalamo-cerebellar network changes at a large temporal scale in GTCS, with FE-FBTS showing more severe network disruption. The study contributed novel imaging evidence for understanding the different epilepsy syndromes associated with generalized seizures.

Temporal variability profiling of the default mode across epilepsy subtypes.

OBJECTIVE: Epilepsies are a group of neurological disorders sharing certain core features, but also demonstrate remarkable pathogenic and symptomatic heterogeneities. Various subtypes of epilepsy have been identified with abnormal shift in the brain default mode network (DMN). This study aims to evaluate the fine details of shared and distinct alterations in the DMN among epileptic subtypes. METHODS: We collected resting-state functional magnetic resonance imaging (MRI) data from a large epilepsy sample (n = 371) at a single center, including temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and genetic generalized epilepsy with generalized tonic-clonic seizures (GGE-GTCS), as well as healthy controls (HC, n = 150). We analyzed temporal dynamics profiling of the DMN, including edge-wise and node-wise temporal variabilities, and recurrent dynamic states of functional connectivity, to identify abnormalities common to epilepsies as well as those specific to each subtype. RESULTS: The analyses revealed that hypervariable edges within the specific DMN subsystem were shared by all subtypes (all PNBS  < .005), and deficits in node-wise temporal variability were prominent in TLE (all t(243) ≤ 2.51, PFDR  < .05) and FLE (all t(302) ≤ -2.65, PFDR  < .05) but relatively weak in GGE-GTCS. Moreover, dynamic states were generally less stable in patients than controls (all P's < .001). SIGNIFICANCE: Collectively, these findings demonstrated general DMN abnormalities common to different epilepsies as well as distinct dysfunctions to subtypes, and provided insights into understanding the relationship of pathophysiological mechanisms and brain connectivity.

Thalamus and focal to bilateral seizures: A multiscale cognitive imaging study.

OBJECTIVE: To investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality. METHODS: FBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 left/58 right), who performed a verbal fluency fMRI task that elicited robust thalamic activation. Thirty-three patients (29%) had experienced at least one FBTCS in the year preceding the investigation. We compared patients with TLE-FBTCS to those without FBTCS via a multiscale approach, entailing analysis of statistical parametric mapping (SPM) 12-derived measures of activation, task-modulated thalamic functional connectivity (psychophysiologic interaction), and graph-theoretical metrics of centrality. RESULTS: Individuals with TLE-FBTCS had less task-related activation of bilateral thalamus, with left-sided emphasis, and left hippocampus than those without FBTCS. In TLE-FBTCS, we also found greater task-related thalamotemporal and thalamomotor connectivity, and higher thalamic degree and betweenness centrality. Receiver operating characteristic curves, based on a combined thalamic functional marker, accurately discriminated individuals with and without FBTCS. CONCLUSIONS: In TLE-FBTCS, impaired task-related thalamic recruitment coexists with enhanced thalamotemporal connectivity and whole-brain thalamic network embedding. Altered thalamic functional profiles are proposed as imaging biomarkers of active secondary generalization.

Peri-ictal hypoxia is related to extent of regional brain volume loss accompanying generalized tonic-clonic seizures.

OBJECTIVES: Hypoxia, or abnormally low blood-oxygen levels, often accompanies seizures and may elicit brain structural changes in people with epilepsy which contribute to central processes underlying sudden unexpected death in epilepsy (SUDEP). The extent to which hypoxia may be related to brain structural alterations in this patient group remains unexplored. METHODS: We analyzed high-resolution T1-weighted magnetic resonance imaging (MRI) to determine brain morphometric and volumetric alterations in people with generalized tonic-clonic seizures (GTCS) recorded during long-term video-electroencephalography (VEEG), recruited from two sites (n = 22), together with data from age- and sex-matched healthy controls (n = 43). Subjects were sub-divided into those with mild/moderate (GTCS-hypox-mild/moderate, n = 12) and severe (GTCS-hypox-severe, n = 10) hypoxia, measured by peripheral oxygen saturation (SpO2 ) during VEEG. Whole-brain voxel-based morphometry (VBM) and regional volumetry were used to assess group comparisons and correlations between brain structural measurements as well as the duration and extent of hypoxia during GTCS. RESULTS: Morphometric and volumetric alterations appeared in association with peri-GTCS hypoxia, including volume loss in the periaqueductal gray (PAG), thalamus, hypothalamus, vermis, cerebellum, parabrachial pons, and medulla. Thalamic and PAG volume was significantly reduced in GTCS patients with severe hypoxia compared with GTCS patients with mild/moderate hypoxia. Brainstem volume loss appeared in both hypoxia groups, although it was more extensive in those with severe hypoxia. Significant negative partial correlations emerged between thalamic and hippocampal volume and extent of hypoxia, whereas vermis and accumbens volumes declined with increasing hypoxia duration. SIGNIFICANCE: Brain structural alterations in patients with GTCS are related to the extent of hypoxia in brain sites that serve vital functions. Although the changes are associative only, they provide evidence of injury to regulatory brain sites related to respiratory manifestations of seizures.

Effects of surgical targeting in laser interstitial thermal therapy for mesial temporal lobe epilepsy: A multicenter study of 234 patients.

OBJECTIVE: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow-up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three-dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image-based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE. METHODS: This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively. RESULTS: Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic-clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome. SIGNIFICANCE: LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.

Impairments of cingulated cortex in the generalized tonic-clonic seizure epilepsy by combining morphological and functional connectivity magnetic resonance imaging.

Previous studies suggested that the patients with generalized tonic-clonic seizure had structural abnormalities in the thalamus, cingulated cortex and some other specific brain regions. Concurrently, the abnormality in thalamocortical network and basal ganglia network has been found in idiopathic generalized epilepsy. The cingulated cortex, a nexus of information processing and regulation in human brain, is implicated in the propagation of generalized spike in IGE and the previous studies have suggested that the structural features and functional connectivity of the cingulated cortex have been changed. The aim of this study was to demonstrate the alterations in the cingulated cortex in generalized tonic-clonic seizure by combining morphological and functional connectivity magnetic resonance imaging. 19 patients with generalized tonic-clonic seizure and 19 age-and gender-matched healthy controls were involved in the study. The three-dimensional high-resolution T1-weighted magnetic resonance imaging data were acquired for voxel-based morphometry analysis, two-sample t-test run on the T1-weighted structural images revealed clusters exhibiting significant decreases in grey-matter volume in the generalized tonic-clonic seizure group, located within the cingulated cortex, thalamus, frontal lobe, temporal lobe, and cerebellum. The decreased gray matter volume in the cingulated cortex indicating that the cingulated cortex has structural impairments in generalized tonic-clonic seizure patients. The bilateral cingulated cortex, as detected with decreased gray matter volume in patients with generalized tonic-clonic seizure through voxel-based morphometry analysis, was selected as seed regions for functional connectivity analysis. Compared with controls, we found decreased functional connectivity to left anterior cingulated cortex (ROI1) in the cuneus, frontal lobe and precentral gyrus. There was no significant result when seeding at the right anterior cingulum gyrus (ROI2). The results of the ROI3 (left middle cingulum) revealed the significantly decreased functional connectivity in the parietal lobe and frontal lobe. Seeding at the ROI4 (right middle cingulum), decreased functional connectivity showed in the occipital lobe, temporal lobe, frontal lobe. Seeding at the ROI5 (left posterior cingulum), decreased functional connectivity showed in the temporal lobe and frontal lobe. Seeding at the ROI6 (right posterior cingulum), decreased functional connectivity showed in the cuneus and frontal lobe. We did not find any increased functional connectivity of the posterior cingulated cortex (ROI3-ROI6) for the generalized tonic-clonic seizure patients in comparison to the controls (p<0.001). Our findings demonstrated that the abnormalities of the functional connectivity were likely to be related to the decreased gray matter volume in the cingulated cortex.

Neuroendocrine tumour metastatic brain disease during immunosuppressive treatment for paraneoplastic GABAB receptor antibodies encephalitis: Is immunosuppression always beneficial?

BACKGROUND: Limbic autoimmune encephalitis (LE) should be considered in any patient with acute or subacute neuropsychiatric manifestations, without other common causes of encephalitis. Y-Aminobutyric-acid-B-receptor (anti-GABABR) antibodies are rarely encountered in association with LE. CASE REPORT: A 74-year-old patient presented with a progressive cognitive degradation and generalized tonic-clonic seizures, with positive anti-GABABR. He declined under immunosuppression treatment. Control magnetic resonance revealed brain lesions, which became positive for pulmonary neuroendocrine tumour metastatic disease. CONCLUSION: The occurrence of diversified neurological manifestations of an underling tumour is difficult to manage. We speculate if in some cases, immunosuppression can itself facilitate tumour progression.

[Epileptic syndromes in childhood associated with secondary generalized tonic-clonic seizures]. / Épilepticheskie sindromy v detskom vozraste, assotsiirovannye s vtorichno-generalizovannymi sudorozhnymi pristupami.

AIM: To study a group of patients with secondary generalized tonic-clonic seizures (SGTCS) in view of nosology, medical history, clinical, electroencephalographic and neuroimaging features. MATERIAL AND METHODS: The study included 471 patients, 244 (51.8%) men and 227 (48.2%) women. RESULTS: SGTCS were observed in many epileptic syndromes. The most frequent were symptomatic focal epilepsy (33.8%), cryptogenic focal epilepsy (23.8%), rolandic epilepsy (12.6%), FEBL-BEDC syndrome (12.3%). Other forms of epilepsy were less frequent. The onset of epilepsy ranged over a wide age range from the first month of life to 18 years. The average age of onset was 5.7±4.96 years. SGTCS as the only type of paroxysms were observed in 28.3% of cases. Two or more types of seizures were observed in 71.7% of patients, three or more types in 39.3%. Epileptiform activity on EEG during long VEM was detected in 91.3% of patients with SGTCS. In 37.2% of patients, benign epileptiform discharges of childhood were recorded. Treatment with antiepileptic drugs (AEP) led to complete remission in 57.1% of cases of epilepsy associated with SGTCS. A reduction of the frequency of seizures by 50% or more was found in 33.6% of patients treated with AEP. No effect was observed in 9.3% of patients. CONCLUSION: Significant differences in the prognosis and therapeutic approaches to specific epileptic syndromes associated with SGTCS necessitate the use of the entire spectrum of diagnostic measures, which should include careful history taking, clinical examination, video-EEG monitoring with the inclusion of sleep dynamics, MRI / CT brain, genetic testing.

Generalized epilepsy syndromes and callosal thickness: Differential effects between patients with juvenile myoclonic epilepsy and those with generalized tonic-clonic seizures alone.

PURPOSE: The definition of two well-studied genetic generalized epilepsy syndromes (GGE) - juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures alone (GTCS) - suggests the absence of structural cerebral abnormalities. Nevertheless, there are various reports of such abnormalities (especially in JME), where effects mainly occur within thalamus and mesial prefrontal regions. This raises the question of whether JME is particularly linked to midline structure abnormalities, which may also involve the corpus callosum. METHOD: We studied callosal morphology in a well-matched sample of 22 JME patients, 15 GTCS patients, and 42 controls (CTL) for all of whom we obtained T1-weighted data on a 3T MRI scanner. More specifically, we measured callosal thickness at 100 equidistant points across the callosal surface, and subsequently compared the three groups (JME, GTCS, and CTL) against each other. RESULTS: Significant differences between JME patients and controls were observed within the callosal genu, anterior midbody, and isthmus, with thinner regions in JME patients. There were no significant differences between GTCS patients and controls, and also not between JME patients and GTCS patients. CONCLUSION: The present outcomes point to callosal abnormalities in JME patients suggesting an impairment of interhemisperic communication between prefrontal, motor, parietal and temporal cortices. These findings further support the notion that structural aberrations are present and differentiated across GGE syndromes, with significant callosal deviations from normality in JME.

Remote preoperative tonic-clonic seizures do not influence outcome after surgery for temporal lobe epilepsy.

OBJECTIVES: Tonic-clonic seizures are associated with greater chance of seizure relapse after anterior temporal lobectomy. We investigated whether the interval between the last preoperative tonic-clonic seizure and surgery relates to seizure outcome in patients with drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: In this retrospective study, patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was categorized as seizure freedom or relapse. The relationship between surgical outcome and the interval between the last preoperative tonic-clonic seizure and surgery was investigated. RESULTS: One-hundred seventy-one patients were studied. Seventy nine (46.2%) patients experienced tonic-clonic seizures before surgery. Receiver operating characteristic curve of timing of the last preoperative tonic-clonic seizure was a moderate indicator to anticipate surgery failure (area under the curve: 0.657, significance; 0.016). The best cutoff that maximizes sensitivity and specificity was 27months; with a sensitivity of 0.76 and specificity of 0.60. Cox-Mantel analysis confirmed that the chance of becoming free of seizures after surgery in patients with no or remote history of preoperative tonic-clonic seizures was significantly higher compared with patients with a recent history (i.e., in 27months before surgery) (p=0.0001). CONCLUSIONS: The more remote the occurrence of preoperative tonic-clonic seizures, the better the postsurgical seizure outcome, with at least a two year gap being more favorable. A recent history of tonic-clonic seizures in a patient with MTLE may reflect more widespread epileptogenicity extending beyond the borders of mesial temporal structures.

Hand postures in primary and secondary generalized tonic-clonic seizures.

OBJECTIVE: To evaluate and identify the frequency of hand postures during generalized convulsions in patients with genetic generalized epilepsy (GGE), localization-related epilepsy (LRE), and nonepileptic attacks (NEA). METHODS: We retrospectively analyzed 98 consecutive videos of generalized convulsions in 62 patients who were admitted for diagnostic video-EEG monitoring. Demographics were recorded, and hand postures were subdivided into fanning, fisting, index-finger pointing (IFP), clawing, and flaccid posturing. Hand postures were then compared between patients with GGE, LRE, and NEA for each stage of the convulsion and for the whole event. RESULTS: In patients with LRE, 96% had IFP, where fanning occurred in 91.3% of GGE (and only at onset), and the flaccid hand posture occurred in 56.0% of NEA. Fisting, fanning, and IFP postures all occurred significantly more frequently during epileptic seizures than during NEA (74.0% vs 32.0%, p = 0.0003; 60.3% vs 20.0%, p = 0.0005; 83.6% vs 12.0%, p < 0.0001). The claw hand posture was present only during NEA, and the flaccid posture occurred significantly more frequently during NEA than during epileptic seizures (56.0% vs 15.1%, p = 0.0001). CONCLUSIONS: Distinct ictal hand or finger posturing is present in patients with GGE, LRE, and NEA. The presence of any fisting, fanning, clawing, IFP, or flaccid hand posturing can help distinguish epileptic seizures from NEA. IFP suggests LRE while fanning with evolution suggests GGE. Overall, hand posturing during seizures provides unique information and aids in the differential diagnosis and classification of epilepsy.

Developmental venous anomaly with contralateral impaired venous drainage in a 17-year-old male. A case report.

Developmental venous anomalies (DVA) drain normal neural tissue and are mostly discovered incidentally. We describe a young patient with a left hemisphere superficial to deep DVA and right hemisphere venous outflow restriction presenting with a seizure. The right hemisphere drainage variation is not typical of a DVA but represents another drainage pattern on the border of normality.

Generalized tonic-clonic seizures in a thalassemic patient with hypoparathyroidism and brain calcinosis.

Acquired hypoparathyroidism (HPT) is a not uncommon complication in patients with b-thalassemia major. The insufficient production of parathyroid hormone is mainly due to iron overload in parathyroid glands. We report a 22-year-old female thalassemic patient referred to our Unit for hypogonadism. During the previous two years she had presented with tonic-clonic seizures. After the second episode the patient was treated with phenytoin and valproate. Laboratory investigations were compatible with a diagnosis of HPT. A computed tomography scan of the head showed diffuse cerebral calcifications in the basal ganglia, frontal subcortical white matter, lentiform nucleus and cerebellum. After treatment with oral calcium supplementation and calcitriol she did not experience any further seizures. In addition, we present a brief review of the literature and report the Authors' recommendations.

Posterior glucose hypometabolism in Lafora disease: early and late FDG-PET assessment.

Establishing an early diagnosis of Lafora disease (LD) is often challenging. We describe two cases of LD presenting as myoclonus and tonic-clonic seizures, initially suggesting idiopathic generalized epilepsy. The subsequent course of the disease was characterized by drug-resistant myoclonic epilepsy, cognitive decline, and visual symptoms, which oriented the diagnosis toward progressive myoclonic epilepsy and, more specifically, LD. Early in the evolution in the first case, and before histopathologic and genetic confirmation of LD in both cases, [18]Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed posterior hypometabolism, consistent with the well-known posterior impairment in this disease. This suggests that FDG-PET could help to differentiate LD in early stages from other progressive myoclonic epilepsies, but confirmation is required by a longitudinal study of FDG-PET in progressive myoclonic epilepsy.

Magnetoencephalography evaluation of febrile seizures in young children.

The aim of this study is to assess any cerebral dysfunction in young children, who experienced febrile seizures, by means of magnetoencephalography. Our study population included 15 children (9 boys, 6 girls) within the age range of 2 to 7 years. The magnetoencephalography data were recorded with a 122-channel biomagnetometer. Equivalent current dipoles were calculated for epileptic spikes on magnetoencephalography recordings according to the single dipole model. Of 15 children, 8 showed equivalent current dipoles that located at the left-temporal, right-temporal, occipital, and frontal lobe, as active regions responsible for febrile seizures. We assumed that the interictal epileptiform discharges are a consequence of febrile seizures. Of course, further study in a larger number of patients is needed to evaluate the exact role of the equivalent current dipoles, in young children, who experienced febrile seizures.

Clinical use of ictal SPECT in secondarily generalized tonic-clonic seizures.

Partial seizures produce increased cerebral blood flow in the region of seizure onset. These regional cerebral blood flow increases can be detected by single photon emission computed tomography (ictal SPECT), providing a useful clinical tool for seizure localization. However, when partial seizures secondarily generalize, there are often questions of interpretation since propagation of seizures could produce ambiguous results. Ictal SPECT from secondarily generalized seizures has not been thoroughly investigated. We analysed ictal SPECT from 59 secondarily generalized tonic-clonic seizures obtained during epilepsy surgery evaluation in 53 patients. Ictal versus baseline interictal SPECT difference analysis was performed using ISAS (http://spect.yale.edu). SPECT injection times were classified based on video/EEG review as either pre-generalization, during generalization or in the immediate post-ictal period. We found that in the pre-generalization and generalization phases, ictal SPECT showed significantly more regions of cerebral blood flow increases than in partial seizures without secondary generalization. This made identification of a single unambiguous region of seizure onset impossible 50% of the time with ictal SPECT in secondarily generalized seizures. However, cerebral blood flow increases on ictal SPECT correctly identified the hemisphere (left versus right) of seizure onset in 84% of cases. In addition, when a single unambiguous region of cerebral blood flow increase was seen on ictal SPECT, this was the correct localization 80% of the time. In agreement with findings from partial seizures without secondary generalization, cerebral blood flow increases in the post-ictal period and cerebral blood flow decreases during or following seizures were not useful for localizing seizure onset. Interestingly, however, cerebral blood flow hypoperfusion during the generalization phase (but not pre-generalization) was greater on the side opposite to seizure onset in 90% of patients. These findings suggest that, with appropriate cautious interpretation, ictal SPECT in secondarily generalized seizures can help localize the region of seizure onset.