Laura Mirandola

Increased cortical BOLD signal anticipates generalized spike and wave discharges in adolescents and adults with idiopathic generalized epilepsies

Purpose:  Electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) coregistration has recently revealed that several brain structures are involved in generalized spike and wave discharges (GSWDs) in idiopathic generalized epilepsies (IGEs). In particular, deactivations and activations have been observed within the so‐called brain default mode network (DMN) and thalamus, respectively. In the present study we analyzed the dynamic time course of blood oxygen level–dependent (BOLD) changes preceding and following 3 Hz GSWDs in a group of adolescent and adult patients with IGE who presented with absence seizures (AS). Our aim was to evaluate cortical BOLD changes before, during, and after GSWD onset.

Recognition of emotions from faces and voices in medial temporal lobe epilepsy

Patients with chronic medial temporal lobe epilepsy (MTLE) can be impaired in different tasks that evaluate emotional or social abilities. In particular, the recognition of facial emotions can be affected (Meletti S, Benuzzi F, Rubboli G, et al. Neurology 2003;60:426-31. Meletti S, Benuzzi F, Cantalupo G, Rubboli G, Tassinari CA, Nichelli P. Epilepsia 2009;50:1547-59). To better understand the nature of emotion recognition deficits in MTLE we investigated the decoding of basic emotions in the visual (facial expression) and auditory (emotional prosody) domains in 41 patients. Results showed deficits in the recognition of both facial and vocal expression of emotions, with a strong correlation between performances across the two tasks. No correlation between emotion recognition and measures of IQ, quality of life (QOLIE-31), and depression (Beck Depression Inventory) was significant, except for a weak correlation between prosody recognition and IQ. These data suggest that emotion recognition impairment in MTLE is not dependent on the sensory channel through which the emotional stimulus is transmitted. Moreover, these findings support the notion that emotional processing is at least partly independent of measures of cognitive intelligence.

An EEG-fMRI Study on the Termination of Generalized Spike-And-Wave Discharges in Absence Epilepsy

Introduction Different studies have investigated by means of EEG-fMRI coregistration the brain networks related to generalized spike-and-wave discharges (GSWD) in patients with idiopathic generalized epilepsy (IGE). These studies revealed a widespread GSWD-related neural network that involves the thalamus and regions of the default mode network. In this study we investigated which brain regions are critically involved in the termination of absence seizures (AS) in a group of IGE patients. Methods Eighteen patients (6 male; mean age 25 years) with AS were included in the EEG-fMRI study. Functional data were acquired at 3T with continuous simultaneous video-EEG recording. Event-related analysis was performed with SPM8 software, using the following regressors: (1) GSWD onset and duration; (2) GSWD offset. Data were analyzed at single-subject and at group level with a second level random effect analysis. Results A mean of 17 events for patient was recorded (mean duration of 4.2 sec). Group-level analysis related to GSWD onset respect to rest confirmed previous findings revealing thalamic activation and a precuneus/posterior cingulate deactivation. At GSWD termination we observed a decrease in BOLD signal over the bilateral dorsolateral frontal cortex respect to the baseline (and respect to GSWD onset). The contrast GSWD offset versus onset showed a BOLD signal increase over the precuneus-posterior cingulate region bilaterally. Parametric correlations between electro-clinical variables and BOLD signal at GSWD offset did not reveal significant effects. Conclusion The role of the decreased neural activity of lateral prefrontal cortex at GSWD termination deserve future investigations to ascertain if it has a role in promoting the discharge offset, as well as in the determination of the cognitive deficits often present in patients with AS. The increased BOLD signal at precuneal/posterior cingulate cortex might reflect the recovery of neural activity in regions that are “suspended” during spike and waves activity, as previously hypothesized.

Non-convulsive status epilepticus of frontal origin as the first manifestation of Hashimoto's encephalopathy

Hashimoto’s encephalopathy is an often misdiagnosed, life threatening, but treatable, condition which improves promptly with steroid therapy. Since clinical manifestations are heterogeneous and non-specific, the diagnosis is often difficult. Several case reports of Hashimoto’s encephalopathy presenting with partial or generalised seizures are described, but only a few have focused on status epilepticus as the first clinical manifestation. We report two patients presenting with repetitive and prolonged seizures characterised by progressive reduction in contact and reactivity associated with frontal/diffuse polyspike-and-wave activities. This condition, which can be interpreted as a formof non-convulsive status epilepticus (NCSE) of frontal origin, was refractory to antiepileptic drugs but responded promptly to high doses of intravenous steroid treatment. In cases of unexplained encephalopathy with EEG documentation of NCSE, the early recognition and treatment of Hashimoto’s encephalopathy may lead to a favourable prognosis.

Centrotemporal spikes during NREM sleep: The promoting action of thalamus revealed by simultaneous EEG and fMRI coregistration☆

Benign childhood epilepsy with centrotemporal spikes (BECTS) has been investigated through EEG–fMRI with the aim of localizing the generators of the epileptic activity, revealing, in most cases, the activation of the sensory–motor cortex ipsilateral to the centrotemporal spikes (CTS). In this case report, we investigated the brain circuits hemodynamically involved by CTS recorded during wakefulness and sleep in one boy with CTS and a language disorder but without epilepsy. For this purpose, the patient underwent EEG–fMRI coregistration. During the “awake session”, fMRI analysis of right-sided CTS showed increments of BOLD signal in the bilateral sensory–motor cortex. During the “sleep session”, BOLD increments related to right-sided CTS were observed in a widespread bilateral cortical–subcortical network involving the thalamus, basal ganglia, sensory–motor cortex, perisylvian cortex, and cerebellum. In this patient, who fulfilled neither the diagnostic criteria for BECTS nor that for electrical status epilepticus in sleep (ESES), the transition from wakefulness to sleep was related to the involvement of a widespread cortical–subcortical network related to CTS. In particular, the involvement of a thalamic–perisylvian neural network similar to the one previously observed in patients with ESES suggests a common sleep-related network dysfunction even in cases with milder phenotypes without seizures. This finding, if confirmed in a larger cohort of patients, could have relevant therapeutic implication.

RF-ablation in periventricular heterotopia-related epilepsy

Drug-resistant focal epilepsy is a common occurrence in patients with gray matter nodular heterotopia (NH), and surgical treatment is often considered in these cases. NH-related epileptogenicity is sustained by complex networks, which may involve the nodules and extralesional cortex in various combinations. Therefore, invasive EEG is usually required to identify the structures involved in seizure generation. It has been reported that surgery may be effective in cases with unilateral lesions, whereas bilateral cases are not optimal candidates for surgical success. Furthermore, violation of cortical and subcortical structures for approaching deep-seated nodules may result in neurological deficits. For these reasons, selective stereotactic ablation with radiofrequency thermocoagulation (RFTC) has been proposed as an alternative option in these patients. In particular, RFTC may be performed by using the same recording intracerebral electrodes implanted for stereo-electro-encephalo-graphy (SEEG) monitoring, with the advantage of a reliable electro-clinical guide. Excellent results on seizures have been initially reported following coagulation of single, unilateral NH. Subsequent experience has indicated that, basing on the evidence of SEEG recording, promising results may be obtained also in more extended unilateral and bilateral cases. In more complex cases, coagulation of both the nodules and of the involved extralesional cortical structures is often required. In a recently reported series, 67% of patients experienced sustained seizure freedom after the procedure. However, post RFTC seizure outcome in complex cases (NH plus other malformations of cortical development) is not as good as in other patterns of NH. RFTC, especially if guided by SEEG evaluation, should be considered as a first-line treatment option in NH-related epilepsy. Satisfactory results may be obtained also in cases not amenable to traditional surgery. The procedure is safe and does not prevent eventual resective surgery in case of failure in seizure control. For these reasons, in patients undergoing SEEG evaluation, electrode arrangement should be planned with the aim to cover as extensively as possible the heterotopic and extralesional areas, which will presumably be the targets of RFTC.

Stereo-EEG: Diagnostic and therapeutic tool for periventricular nodular heterotopia epilepsies

Periventricular nodular heterotopias (PNHs) are malformations of cortical development related to neuronal migration disorders, frequently associated with drug‐resistant epilepsy (DRE). Stereo‐electroencephalography (SEEG) is considered a very effective step of the presurgical evaluation, providing the recognition of the epileptogenic zone (EZ). At the same time, via the intracerebral electrodes it is possible to perform radiofrequency thermocoagulation (SEEG‐guided RF‐TC) with the aim of ablating and/or disrupting the EZ. The purpose of this study was to evaluate both the relationships between PNH and the EZ, and the efficacy of SEEG‐guided RF‐TC.

Long-term surgery outcome for epilepsy and psychogenic nonepileptic seizures in a child with anterior cingulate gyrus dysplasia

We present the case of a 13-year-old child with nocturnal frontal lobe epilepsy (NFLE) related to a right cingulate gyrus cortical dysplasia, who also presented with psychogenic nonepileptic seizures (PNES) and interictal antisocial behavior. The association of drug-resistant epilepsy with behavioral disorders is well established, but the role of epilepsy surgery in these patients is still controversial, especially in children. The key finding is represented by the excellent long-term outcome on both epilepsy and behavioral dysfunction after the surgical excision of the cingulate gyrus cortical dysplasia.

Neuroimaging of status epilepticus

In the past 2 decades we have observed an extensive use of different neuroimaging techniques to evaluate patients with status epilepticus. Magnetic resonance imaging (MRI) in particular may show a broad spectrum of abnormalities that are either the causes or the consequences of sustained epileptic activity. Neuroimaging techniques can offer a contribution both in the clinical management of individual patients, identifying hemodynamic patterns that support the diagnosis, and also in the recognition of periictal reversible or irreversible alterations. For the future it is necessary to develop larger and prospective studies in which imaging techniques and electroencephalography (EEG) recordings are acquired closely to understand which EEG patterns are related to imaging biomarkers of neuronal damage.