Lorenzo Ferri

Tailored surgery for drug-resistant epilepsy due to temporal pole encephalocele and microdysgenesis

Marco Giulioni *, Laura Licchetta , Francesca Bisulli , Guido Rubboli , Barbara Mostacci , Gianluca Marucci , Matteo Martinoni , Lorenzo Ferri , Lilia Volpi , Fabio Calbucci , Agostino Baruzzi , Paolo Tinuper b,c a IRCCS Istituto delle Scienze Neurologiche di Bologna, Division of Neurosurgery, AUSL di Bologna, Italy b IRCCS Istituto delle Scienze Neurologiche di Bologna, AUSL di Bologna, Italy Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy d IRCCS Istituto delle Scienze Neurologiche di Bologna, Division of Neurology, AUSL di Bologna, Italy Danish Epilepsy Center, Epilepsihospitalet, Dianalund, Denmark f Section of Pathology ‘‘M. Malpighi’’ at Bellaria Hospital, Department of Biomedical and Neuro Motor Sciences, University of Bologna, Bologna, Italy

Incidence of sudden unexpected death in nocturnal frontal lobe epilepsy: a cohort study.

Highlights • We assessed sudden unexpected death in epilepsy in nocturnal frontal lobe epilepsy.• The incidence of SUDEP in NFLE was no higher than that of other epilepsy populations.• The lower than expected risk of SUDEP might reflect a low occurrence of GTCS in NFLE.

Auditory aura in nocturnal frontal lobe epilepsy: a red flag to suspect an extra-frontal epileptogenic zone

Highlights • Eleven out of 165 nocturnal frontal lobe epilepsy (NFLE) patients reported an auditory aura as initial ictal symptom.• Extra-frontal origin was documented in 55% of NFLE patients with auditory aura.• Six patients with defined epileptogenic zone had a left temporal origin of seizures.• Auditory aura may be a symptom suggesting an extra-frontal epileptogenic zone.

Non-24-Hour Sleep-Wake Rhythm Disorder and Melatonin Secretion Impairment in a Patient With Pineal Cyst

ABSTRACT We report the case of a 14-year-old girl with a wide non-compressive pineal cyst, associated with the inability to control her sleep-wake schedule. Actigraphic monitoring showed a 24-hour free-running disorder (tau 26.96 hours). A 24-hour serum melatonin curve assay, with concomitant video-polysomnographic and body-core temperature monitoring, was performed. Melatonin curve showed a blunted nocturnal peak, lower total quantity of melatonin, and prolonged melatonin secretion in the morning, with normal temperature profile and sleep parameters. Treatment with melatonin up to 14 mg at bedtime was initiated with complete realignment of the sleep-wake rhythm (tau 23.93 hours). The role of the pineal cyst in the aforementioned alteration of melatonin secretion and free-running disorder remains controversial, but our case supports the utility of monitoring sleep/wake, temperature, and melatonin rhythms in the diagnostic work-up of pineal cysts associated with free-running disorder.

Brain functional connectivity in sleep-related hypermotor epilepsy

Objectives To evaluate functional connectivity (FC) in patients with sleep-related hypermotor epilepsy (SHE) compared to healthy controls. Methods Resting state fMRI was performed in 13 patients with a clinical diagnosis of SHE (age = 38.3 ± 11.8 years, 6 M) and 13 matched healthy controls (age = 38.5 ± 10.8 years, 6 M). Data were first analysed using probabilistic independent component analysis (ICA), then a graph theoretical approach was applied to assess topological and organizational properties at the whole brain level. We evaluated node degree (ND), betweenness centrality (BC), clustering coefficient (CC), local efficiency (LE) and global efficiency (GE). The differences between the two groups were evaluated non-parametrically. Results At the group level, we distinguished 16 RSNs (Resting State Networks). Patients showed a significantly higher FC in sensorimotor and thalamic regions (p < 0.05 corrected). Compared to controls, SHE patients showed no significant differences in network global efficiency, while ND and BC were higher in regions of the limbic system and lower in the occipital cortex, while CC and LE were higher in regions of basal ganglia and lower in limbic areas (p < 0.05 uncorrected). Discussion and conclusions The higher FC of the sensorimotor cortex and thalamus might be in agreement with the hypothesis of a peculiar excitability of the motor cortex during thalamic K-complexes. This sensorimotor-thalamic hyperconnection might be regarded as a consequence of an alteration of the arousal regulatory system in SHE. An altered topology has been found in structures like basal ganglia and limbic system, hypothesized to be involved in the pathophysiology of the disease as suggested by the dystonic-dyskinetic features and primitive behaviours observed during the seizures.

Effect of valproic acid on perampanel pharmacokinetics in patients with epilepsy

We prospectively examined the effect of antiepileptic (AED) cotherapy on steady state plasma concentrations of perampanel (PMP) in epileptic patients. We classified AEDs as strong enzyme inducers (carbamazepine, phenobarbital, phenytoin, oxcarbazepine), not strong enzyme inducers/not inhibitors (levetiracetam, lamotrigine, topiramate, rufinamide, lacosamide, zonisamide, clobazam), and enzyme inhibitors (valproic acid [VPA]). The main outcome was the comparison of PMP plasma concentration to weight‐adjusted dose ratio (C/D; [μg/mL]/mg kg−1 d−1) among comedication subgroups. From 79 patients (42 females, 37 males) aged (mean ± standard deviation) 33 ± 13 years (range = 12‐66 years), 114 plasma samples were collected. Twenty‐eight patients (44 samples) were cotreated with enzyme inducers (group A), 21 (27 samples) with not strong enzyme inducers/not inhibitors (group B), 21 (31 samples) with not strong enzyme inducers/not inhibitors + VPA (group C), and 9 (12 samples) with enzyme inducers + VPA (group D). PMP C/D was reduced (−56%, P < .001) in group A (1.79 ± 0.80) versus group B (4.05 ± 2.16) and increased (P < .001) in group C (6.72 ± 4.04) compared with groups A (+275%), B (+66%), and D (2.76 ± 2.00, +143%). Our study documents the unpublished higher PMP C/D in patients cotreated with VPA. These findings have both theoretical relevance, suggesting better characterization of PMP metabolic pathways with ad hoc studies, and clinical usefulness in managing patients on AED polytherapy.

Proton MR spectroscopy in patients with sleep-related hypermotor epilepsy (SHE): Evidence of altered cingulate cortex metabolism

Study Objectives To identify structural and/or metabolic alterations in patients with sleep-related hypermotor epilepsy (SHE) using magnetic resonance imaging (MRI) and proton MR spectroscopy (1H-MRS). Methods Nineteen SHE patients (seven males; 34.7 ± 9.7 years, mean age ± standard deviation) and 17 matched healthy volunteers (seven males; 34.0 ± 8.9 years) were included in the study. In all patients, the diagnosis of SHE was confirmed by video-polysomnographic recording of seizures. Semiology, seizure frequency, and therapy were assessed for all patients. For each recruited participant, structural MRI and 1H-MRS sequences were acquired. 1H-MRS was performed on two regions of interest: the medial thalamus and the anterior cingulate gyrus. Results At examination, five patients were seizure free. In the remainder, seizure frequency ranged from yearly to multiple episodes per night. Brain MRI was normal in all patients but one. The ratio of N-acetyl-aspartate/Creatine (NAA/Cr) was significantly reduced in the anterior cingulate cortex in patients compared to controls (p < .05). Thalamic NAA/Cr showed no differences between patients and controls. Regression analysis showed that NAA/Cr in the anterior cingulate gyrus correlated with seizure frequency (p < .05), being lower in patients with higher seizure frequency. Conclusions Given the absence of structural MR changes, our 1H-MRS data point to a functional NAA reduction in the cingulate cortex of SHE patients, more severe in those patients with higher seizure frequency and thus supporting the involvement of the anterior mesial structures in the pathophysiology of SHE.

A stereo EEG study in a patient with sleep-related hypermotor epilepsy due to DEPDC5 mutation

PURPOSE Dishevelled EGL-10 and pleckstrin domain-containing protein 5 (DEPDC5) mutations are found in a wide spectrum of focal epilepsies ranging from epilepsy caused by malformation of cortical development to non-lesional epilepsy, including sleep-related hypermotor epilepsy (SHE). A surgical approach has been anecdotally reported in patients with DEPDC5 mutations, but most of these cases had a lesional etiology. METHODS We describe a stereo-EEG (SEEG) study in a patient with drug-resistant/non-lesional SHE. Patient was screened for known mutations associated with SHE. RESULTS SEEG disclosed bilateral synchronous and independent activity prevailing on the right central-anterior cingulate cortex, without a clear spatially defined epileptogenic zone. Due to the lack of a clear epileptogenic zone, surgery was contraindicated. Years later a DEPDC5 mutation was identified. CONCLUSION We suggest that genetic analysis should be considered before performing SEEG study in a patient with drug resistant non-lesional SHE, in the presence of seizures in wakefulness and unclear anatomo-electroclinical correlation. If DEPDC5 mutations are identified, the presurgical evaluation should be tailored to look for MRI-negative focal cortical dysplasia and a wide epileptogenic network. The appropriate management and potential benefit of surgery for genetic non-lesional epilepsy have yet to be clarified.