Chiara Campana

Slow Activity in Focal Epilepsy During Sleep and Wakefulness

Introduction. We aimed to test differences between healthy subjects and patients with respect to slow wave activity during wakefulness and sleep. Methods. Fifteen patients affected by nonlesional focal epilepsy originating within temporal areas and fourteen matched controls underwent a 24-hour EEG recording. We studied the EEG power spectral density during wakefulness and sleep in delta (1-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (12-15 Hz), and beta (16-20 Hz) bands. Results. During sleep, patients with focal epilepsy showed higher power from delta to beta frequency bands compared with controls. The effect was widespread for alpha band and above, while localized over the affected hemisphere for delta (sleep cycle 1, P = .006; sleep cycle 2, P = .008; sleep cycle 3, P = .017). The analysis of interhemispheric differences showed that the only frequency band stronger over the affected regions was the delta band during the first 2 sleep cycles (sleep cycle 1, P = .014; sleep cycle 2, P = .002). During wakefulness, patients showed higher delta/theta activity over the affected regions compared with controls. Conclusions. Patients with focal epilepsy showed a pattern of power increases characterized by a selective slow wave activity enhancement over the epileptic regions during daytime and sleep. This phenomenon was stronger and asymmetric during the first sleep cycles.

A novel c132‐134del mutation in Unverricht‐Lundborg disease and the review of literature of heterozygous compound patients

Unverricht‐Lundborg disease or progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessive disease caused by mutation of the cystatin B gene (CSTB), located on chromosome 21q22.3. The most common mutation is an expansion of unstable dodecamer repetition (CCCCGCCCCGCG), whereas other types of mutations are rare. Among these, heterozygous compound mutations are described to induce a more severe phenotype than that of homozygous dodecameric repetition. We report two siblings affected by heterozygous compound mutations carrying a novel mutation of the deletion of three nucleotides in exon 2 of the gene in position 132–134 of the coding sequence (c.132‐134del) in the allele not including the dodecamer repetition. This mutation results in the loss of two amino acid residues and insertion of an asparagine in position 44 (p.Lys44_Ser45delinsAsn). Our patients presented a very different clinical picture. The male patient had a severe myoclonus, drug‐resistant epilepsy and psychiatric comorbidity, while his affected sister had only very rare seizures and sporadic myoclonic jerks at awakening. The revision of literature about heterozygous compound EPM1 patients confirms this gender phenotypic expressivity, with female patients carrying less severe symptoms than male patients. These data lead to the hypothesis of complex gender‐specific factors interacting with CSTB expressivity in EPM1 patients.

Hyperventilation induces sympathetic overactivation in mesial temporal epilepsy

OBJECTIVE Hyperventilation (HV) during electroencephalography (EEG) is a standard clinical procedure to trigger seizures in patients affected by mesial temporal lobe epilepsy (MTLE). Despite the pathophysiology of this susceptibility to HV is not definitively understood, it may be hypothesized to be related to ictal and interictal sympathetic nervous system abnormalities, the presence of which is well known in MTLE patients. In order to test this hypothesis we investigated the HV effect on heart rate variability (HRV) in a group of MTLE patients, compared to a matched group of healthy controls. MATERIAL AND METHODS Forty patients affected by MTLE and 40 age- and sex-matched controls were enrolled in the study. In those subjects, a standard electroencephalographic recording has been acquired and the high and the low frequency components (HF, LF) of heart rate variability (HRV) and their ratio (LF/HF) have been analyzed at rest and during the HV. Indeed, LF/HF is a reliable index of sympathetic tone modulation. RESULTS HRV did not differ between MTLE and healthy subjects at rest, whereas HV induced a significant LF/HF increase only in MTLE. Within the MTLE group, males showed higher LF/HF increase during HV respect to females, while no differences related to the side of the epileptic focus were found. DISCUSSION MTLE patients showed an increased sympathetic response to HV compared to healthy subjects. HRV analysis points towards an autonomic overactivation as a pathophysiological pathway subtending seizure triggered by hyperventilation in MTLE. Autonomic susceptibility in MTLE may help to explain the increased prevalence of arrhythmic events in these patients, potentially predisposing to Sudden Unexpected Death in Epilepsy (SUDEP).

Osteomalacic myopathy: An uncommon side effect of antiepileptic drugs

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Dengue encephalitis presenting with nonconvulsive status epilepticus: A case report

Dengue fever is endemic in tropical/sub-tropical areas of the orld and the global incidence is increasing. It is an infective isorder caused by one of the 4 serotypes of Dengue virus (famly Flaviviridae), transmitted by mosquitoes of the genus Aedes. t is characterised by a wide spectrum of clinical manifestaions, ranging from asymptomatic infection to life-threatening engue haemorrhagic fever and dengue shock syndrome, which ncludes overt central neurological dysfunction, with encephalitis nd seizures. Here we report a case of dengue encephalitis with n unusual clinical manifestation: a nonconvulsive status epilepicus (NCSE). To our knowledge, the association between dengue ncephalitis and NCSE has not been previously described. Our bservation shows that sometimes the early manifestations of the nfection could be mild and subtle, also in the case of direct CNS nvolvement, making diagnosis very challenging.

Calcium metabolism serum markers in adult patients with epilepsy and the effect of vitamin D supplementation on seizure control

PURPOSE To evaluate serum markers of calcium metabolism in adult patients with epilepsy (PWE) treated with antiepileptic drugs (AEDs) and the effect of vitamin D supplementation on seizure frequency. METHODS Serum levels of calcium, phosphate, intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D (25[OH]D) were compared in 160 PWE on chronic therapy with AEDs and 42 matched controls. Blood concentrations were analyzed taking into account the different features of epilepsy and treatment. Finally, the effect of vitamin D supplementation on seizure control was assessed in a subgroup of 48 drug resistant epileptic patients. RESULTS PWE showed lower serum levels of 25[OH]D compared to control subjects (p < .001). Only 25% PWE showed normal 25[OH]D levels, whereas 41,9% had a vitamin D failure and 33,1% a vitamin D deficiency (p < .001). 25[OH]D serum levels depended on treatment duration, number of medications and enzyme-inducing AEDs (p < .001, p < .001, p = .013, respectively). Polytherapy and enzyme-inducing AEDs showed more detrimental effects on the 25[OH]D and calcium serum levels. The administration of vitamin D failed to significantly improve seizure control. CONCLUSIONS PWE show deficiency of vitamin D. The serum levels of 25[OH]D depend on the features and duration of AEDs treatment. Vitamin D administration in drug resistant epilepsy patients does not result in a reduction of seizure frequency.

Functional Clustering approach for the analysis of Stereo-EEG activity patterns in correspondence of epileptic seizures

In this study, a functional clustering approach is proposed and tested for the identification of brain functional networks emerging during sleep-related seizures. Stereo-EEG signals recorded in patients with Type II Focal Cortical Dysplasia (FCD type II), were analyzed. This novel approach is able to identify the network configuration changes in pre-ictal and early ictal periods, by grouping Stereo-EEG signals on the basis of the Cluster Index, after wavelet multiscale decomposition. Results showed that the proposed method is able to detect clusters of interacting leads, mainly overlapped on the Epileptogenic Zone (EZ) identified by a clinical expert, with distinctive configurations related to analyzed frequency ranges. This suggested the presence of coupling activities between the elements of the epileptic system at different frequency scales.

Measuring autonomic involvement related to seizure onset in Focal Cortical Dysplasia type II

The research here presented aims to the investigation of the Autonomic Nervous System (ANS) and of the sympatho-vagal balance during sleep-related seizures in patients affected by Focal Cortical Dysplasia (FCD) type II. Heart Rate Variability (HRV) signal was recorded during sleep together with S-EEG (stereo EEG) acquisitions performed for pre-surgical evaluation. The sympatho-vagal balance was estimated in pre-ictal, ictal and post-ictal time, by means of parameters in the time and in the frequency domain. The results here presented are related to 10 epileptic seizures occurring during the same night in one patient. The obtained results testify a significant decrease (p < 0.005) in the RR mean value and standard deviation during the ictal and post-ictal periods in respect to the inter-ictal phase, and a significant decrease (p < 0.001) in the HF(%) power between inter-ictal and post-ictal periods. All these findings are associated to a sympathetic activation and to a vagal drive reduction. A deeper knowledge of the correlations between ANS and epilepsy can lead to better understand the causes of SUDEP (Sudden Unexpected Death in Epilepsy); can contribute to the development of methods for the detection and prediction of epileptic seizures and help to evaluate the effects of vagal nerve stimulation used in those cases in which the patient is not an ideal candidate for surgery.

62. Efficacy of cathodal transcranial direct current stimulation in drug-resistant epilepsy: A proof of principle

It has been proved that Transcranial DCS (tDCS) can modulate cortical excitability, enhancing or decreasing, respectively by anodal or cathodal polarity. The short-term and lasting alterations induced by tDCS are strictly related to the charge density, duration of stimulation and the depth of neuron below the skull. Epilepsy represents a pathophysiological model of unbalanced relation between cortical excitation and inhibition. In this line, tDCS can be exploited to counterbalance the neuronal hyper-excitation through electric neural modulation. This paper aims at providing the efficacy of cathodal tDCS in reducing seizures’ frequency in drug-resistant focal epilepsy. The study was single blind and sham-controlled and compared seizure rate in the 7 days before and after tDCS and after sham in a cross-over design. 9 patients affected by focal resistant epilepsy were enrolled. After tDCS 3 out 9 patients have not any change in seizure rate. 6 patients reduced their seizure frequency >50%. No significant modification were recorded after sham. This study represents the proof that cathodal tDCS may be efficient in reducing seizures’frequency in focal resistant epilepsy.