Regional White Matter Atrophy Correlates with Spike Activity in Encephalopathy Related to Status Epilepticus During Slow Sleep (ESES) After Early Thalamic Lesions.

Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is an age-related, epileptic syndrome, which associates cognitive/behavioral disturbances with a peculiar pattern of spike activity. One promising line of research is the study of ESES in cases of early thalamic lesions. We studied 7 ESES patients with unilateral thalamic lesions using magnetic resonance imaging to assess regional white matter (WM) and thalamic nuclei volume differences, and long-term electroencephalogram recordings to localize the epileptogenic cortex. N170 event-related potentials were used to demonstrate the dysfunctional character of the WM abnormalities. Diffusion-weighted images in a subset of 4 patients were used to parcellate the thalamus and evaluate volume asymmetries, based on cortical connectivity. Large WM regional atrophy in the hemisphere with the thalamic lesion was associated with both cortical dysfunction and epileptic activity. A correlation was demonstrated between lesions in the pulvinar and the mediodorsal thalamic nuclei and WM atrophy of the corresponding cortical projection areas. We propose that these abnormalities are due to the widespread structural disconnection produced by the thalamic lesions associated to a yet unknown age-dependent factor. Further exploration of WM regional atrophy association with the spike activity in other etiologies could lend support to the cortical disconnection role in ESES genesis.

Interictal spike quantification in continuous spike-wave of sleep (CSWS): Clinical usefulness of a wearable EEG device.

INTRODUCTION: Continuous spike-wave of sleep (CSWS) syndrome is one of the most common epileptic encephalopathies of childhood. Because the associated cognitive/behavioral disturbances relate more to the amount of spike activity than of seizures, methods of spike quantification gained relevance in diagnosis and monitoring treatment. The conventional methodology for quantification of spike index (SI) relies on repeated full 10-20 long-term ambulatory electroencephalography (aEEG), which is both expensive and poorly tolerated. OBJECTIVE: The objectives of this study were to demonstrate the clinical value of repeated SI assessments in CSWS and to build and validate a wearable device allowing inexpensive and well-tolerated, repeated quantifications. METHODS: A group of N = 38 patients with CSWS were submitted to repeated SI quantifications based on aEEG, as seen fit by the medical clinical assistant. Responses to therapy with corticosteroids (N = 10), sulthiame (N = 7), and the ketogenic diet (N = 3) were monitored. We used a conventional method based on a semiautomatic template match spike search. The individual variability in time spans of days (N = 4) or months (N = 10) was assessed and used to determine the meaningful neurophysiological responses to the diverse therapies. A wearable device capable of recording 2 bipolar EEG channels for 24 h was used to simplify SI quantification. RESULTS: Corticosteroids produced the most powerful SI reduction, but a large individual variability in both amount and time of onset of clinical response with some patients exhibiting recurrence shortly after therapy. A more frequent sampling of SI would provide a more accurate follow-up, with clinical benefit. The comparison of the SI obtained from standard 10-20 electrodes and 2 bipolar EEG channel subsets in aEEG or between the 10-20 and simultaneous wearable recordings, demonstrated that the new method provides an accurate SI quantification. CONCLUSIONS: A wearable EEG device with 2 bipolar channels simplifies the process of obtaining repeated SI quantification allowing a more accurate follow-up of spike activity in the clinical setting.

Feasibility of focal transcranial DC polarization with simultaneous EEG recording: preliminary assessment in healthy subjects and human epilepsy.

We aimed to investigate the feasibility of an experimental system for simultaneous transcranial DC stimulation (tDCS) and EEG recording in human epilepsy. We report tolerability of this system in a cross-over controlled trial with 15 healthy subjects and preliminary effects of its use, testing repeated tDCS sessions, in two patients with drug-refractory Continuous Spike-Wave Discharges During Slow Sleep (CSWS). Our system combining continuous recording of the EEG with tDCS allows detailed evaluation of the interictal activity during the entire process. Stimulation with 1 mA was well-tolerated in both healthy volunteers and patients with refractory epilepsy. The large reduction in interictal epileptiform EEG discharges in the two subjects with epilepsy supports further investigation of tDCS using this combined method of stimulation and monitoring in epilepsy. Continuous monitoring of epileptic activity throughout tDCS improves safety and allows detailed evaluation of epileptic activity changes induced by tDCS in patients.

Origin of frontal lobe spikes in the early onset benign occipital lobe epilepsy (Panayiotopoulos syndrome).

OBJECTIVE: Early onset benign occipital lobe epilepsy (Panayiotopoulos syndrome [PS]) is a common and easily recognizable epilepsy. Interictal EEG spike activity is often multifocal but most frequently localized in the occipital lobes. The origin and clinical significance of the extra-occipital spikes remain poorly understood. METHODS: Three patients with the PS and interictal EEG spikes with frontal lobe topography were studied using high-resolution EEG. Independent component analysis (ICA) was used to decompose the spikes in components with distinct temporal dynamics. The components were mapped in the scalp with a spline-laplacian algorithm. RESULTS: The change in scalp potential topography from spike onset to peak, suggests the contribution of several intracranial generators, with different kinetics of activation and significant overlap. ICA was able to separate the major contributors to frontal spikes and consistently revealed an early activating group of components over the occipital areas in all the patients. The local origin of these early potentials was established by the spline-laplacian montage. CONCLUSIONS: Frontal spikes in PS are consistently associated with early and unilateral occipital lobe activation, suggesting a postero-anterior spike propagation. SIGNIFICANCE: Frontal spikes in the PS represent a secondary activation triggered by occipital interictal discharges and do not represent an independent focus.

Analysis of the dynamics and origin of epileptic activity in patients with tuberous sclerosis evaluated for surgery of epilepsy.

OBJECTIVE: The epilepsies associated with the tuberous sclerosis complex (TSC) are very often refractory to medical therapy. Surgery for epilepsy is an effective alternative when the critical link between the localization of seizure onset in the scalp and a particular cortical tuber can be established. In this study we perform analysis of ictal and interictal EEG to improve such link. METHODS: The ictal and interictal recordings of four patients with TSC undergoing surgery for epilepsy were submitted to independent component analysis (ICA), followed by source analysis, using the sLORETA algorithm. The localizations obtained for the ictal EEG and for the average interictal spikes were compared. RESULTS: The ICA of ictal EEG produced consistent results in different events, and there was good agreement with the tubers that were successfully removed in three of the four patients (one patient refused surgery). In some patients there was a large discrepancy between the localization of ictal and interictal sources. The interictal activity produced more widespread source localizations. CONCLUSIONS: The use of ICA of ictal EEG followed by the use of source analysis methods in four cases of epilepsy and TSC was able to localize the epileptic generators very near the lesions successfully removed in surgery for epilepsy. SIGNIFICANCE: The ICA of ictal EEG events may be a useful add-on to the tools used to establish the connection between epileptic scalp activity and the cortical tubers originating it, in patients with TSC considered for surgery of epilepsy.

Analysis of the generators of epileptic activity in early-onset childhood benign occipital lobe epilepsy.

OBJECTIVE: The Panayiotopoulos type of idiopathic occipital epilepsy has peculiar and easily recognizable ictal symptoms, which are associated with complex and variable spike activity over the posterior scalp areas. These characteristics of spikes have prevented localization of the particular brain regions originating clinical manifestations. We studied spike activity in this epilepsy to determine their brain generators. METHODS: The EEG of 5 patients (ages 7-9) was recorded, spikes were submitted to blind decomposition in independent components (ICs) and those to source analysis (sLORETA), revealing the spike generators. Coherence analysis evaluated the dynamics of the components. RESULTS: Several ICs were recovered for posterior spikes in contrast to central spikes which originated a single one. Coherence analysis supports a model with epileptic activity originating near lateral occipital area and spreading to cortical temporal or parietal areas. CONCLUSIONS: Posterior spikes demonstrate rapid spread of epileptic activity to nearby lobes, starting in the lateral occipital area. In contrast, central spikes remain localized in the rolandic fissure. SIGNIFICANCE: Rapid spread of posterior epileptic activity in the Panayitopoulos type of occipital lobe epilepsy is responsible for the variable and poorly localized spike EEG. The lateral occipital cortex is the primary generator of the epileptic activity.

Analysis of the EEG dynamics of epileptic activity in gelastic seizures using decomposition in independent components.

OBJECTIVE: Gelastic seizures are a frequent and well established manifestation of the epilepsy associated with hypothalamic hamartomas. The scalp EEG recordings very seldom demonstrate clear spike activity and the information about the ictal epilepsy dynamics is limited. In this work, we try to isolate epileptic rhythms in gelastic seizures and study their generators. METHODS: We extracted rhythmic activity from EEG scalp recordings of gelastic seizures using decomposition in independent components (ICA) in three patients, two with hypothalamic hamartomas and one with no hypothalamic lesion. Time analysis of these rhythms and inverse source analysis was done to recover their foci of origin and temporal dynamics. RESULTS: In the two patients with hypothalamic hamartomas consistent ictal delta (2-3 Hz) rhythms were present, with subcortical generators in both and a superficial one in a single patient. The latter pattern was observed in the patient with no hypothalamic hamartoma visible in MRI. The deep generators activated earlier than the superficial ones, suggesting a consistent sub-cortical origin of the rhythmical activity. CONCLUSIONS: Our data is compatible with early and brief epileptic generators in deep sub-cortical regions and more superficial ones activating later. SIGNIFICANCE: Gelastic seizures express rhythms on scalp EEG compatible with epileptic activity originating in sub-cortical generators and secondarily involving cortical ones.

A single neurotoxic dose of methamphetamine induces a long-lasting depressive-like behaviour in mice.

Methamphetamine (METH) triggers a disruption of the monoaminergic system and METH abuse leads to negative emotional states including depressive symptoms during drug withdrawal. However, it is currently unknown if the acute toxic dosage of METH also causes a long-lasting depressive phenotype and persistent monoaminergic deficits. Thus, we now assessed the depressive-like behaviour in mice at early and long-term periods following a single high METH dose (30 mg/kg, i.p.). METH did not alter the motor function and procedural memory of mice as assessed by swimming speed and escape latency to find the platform in a cued version of the water maze task. However, METH significantly increased the immobility time in the tail suspension test at 3 and 49 days post-administration. This depressive-like profile induced by METH was accompanied by a marked depletion of frontostriatal dopaminergic and serotonergic neurotransmission, indicated by a reduction in the levels of dopamine, DOPAC and HVA, tyrosine hydroxylase and serotonin, observed at both 3 and 49 days post-administration. In parallel, another neurochemical feature of depression--astroglial dysfunction--was unaffected in the cortex and the striatal levels of the astrocytic protein marker, glial fibrillary acidic protein, were only transiently increased at 3 days. These findings demonstrate for the first time that a single high dose of METH induces long-lasting depressive-like behaviour in mice associated with a persistent disruption of frontostriatal dopaminergic and serotonergic homoeostasis.

Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities.

PURPOSE: SCN1A is the most clinically relevant epilepsy gene, most mutations lead to severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). We studied 132 patients with epilepsy syndromes with seizures precipitated by fever, and performed phenotype-genotype correlations with SCN1A alterations. METHODS: We included patients with SMEI including borderline SMEI (SMEB), GEFS+, febrile seizures (FS), or other seizure types precipitated by fever. We performed a clinical and genetic study focusing on SCN1A, using dHPLC, gene sequencing, and MLPA to detect genomic deletions/duplications on SMEI/SMEB patients. RESULTS: We classified patients as: SMEI/SMEB = 55; GEFS+= 26; and other phenotypes = 51. SCN1A analysis by dHPLC/sequencing revealed 40 mutations in 37 SMEI/SMEB (67%) and 3 GEFS+ (11.5%) probands. MLPA showed genomic deletions in 2 of 18 SMEI/SMEB. Most mutations were de novo (82%). SMEB patients carrying mutations (8) were more likely to have missense mutations (62.5%), conversely SMEI patients (31) had more truncating, splice site or genomic alterations (64.5%). SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS compared to those with missense mutations and without mutations (p = 0.00007, ANOVA test). None of the remaining patients with seizures precipitated by fever carried SCN1A mutations. CONCLUSION: We obtained a frequency of 71%SCN1A abnormalities in SMEI/SMEB and of 11.5% in GEFS+ probands. MLPA complements DNA sequencing of SCN1A increasing the mutation detection rate. SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS. This study confirms the high sensitivity of SCN1A for SMEI/SMEB phenotypes.