Background and purpose Misdiagnosis of refractory epilepsy ( rE ) is common and such patients experience a long diagnostic delay. Our aim was to identify key clinical/laboratory factors in order to obtain an alternative diagnosis in patients referred for rE . Methods Between January 2010 and December 2015, 125 consecutive patients with a diagnosis of rE were prospectively enrolled. All patients underwent a comprehensive neurological, neuropsychiatric and cardiological evaluation, and had an observation time of at least 1 year after the study entry. Results Diagnosis of rE was confirmed in 104/125 (83.2%) patients (55 women, mean age 38.8 ± 14.3 years). Thirteen/125 patients (10.4%, seven women, mean age 50.8 ± 20.9) were diagnosed with syncope, which was cardiac/cardio inhibitory in 9/13 (69%). The remaining 8/125 patients (6.4%, six women, mean age 41.2 ± 14.6 years) were diagnosed with psychogenic non‐epileptic seizures. Age at onset had a high accuracy in differentiating patients with syncope from others, with the best cut‐off age at 35 years and above. Abnormal brain magnetic resonance imaging ( MRI ) had a significant yield of about 70% in rE . A diagnostic model including age at onset and brain MRI was highly accurate in differentiating patients with syncope from others. In patients with cardiac/cardio inhibitory syncope, the point score of historical features was ≥1 and falsely favoured the diagnosis of epileptic seizures. Conclusions This prospective cohort study identifies rE mimics who are at high risk of morbidity and mortality. rE starting in adulthood should raise a high suspicion of cardiac syncope. Brain MRI is accurate in differentiating rE from other conditions.

The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non-epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients' representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age-related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive-behavioural therapy as a first-line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non-epileptic seizure management should be multidisciplinary. High-quality long-term studies are needed to standardize PNES management.

Background and purposeThe presence of a continuum between physiological déjà vu (DV) and epileptic DV is still not known as well as epidemiological data in the Italian population. The aim was to identify the epidemiological distribution of DV in Italy, and secondly to look for specific features of DV able to discriminate between epileptic and non‐epileptic DV.MethodsIn all, 1000 individuals, 543 healthy controls (C) (313 women; age 40 ± 15 years) and 457 patients with epilepsy (E) (260 women; age 39 ± 14 years), were prospectively recruited from 10 outpatient neurological clinics throughout Italy. All populations were screened using the Italian Inventory for Déjà Vu Experiences Assessment (I‐IDEA) test and E and pairwise C underwent a comprehensive epilepsy interview.ResultsOf E, 69% stated that they experienced ‘recognition’ and 13.2% reported that this feeling occurred from a few times a month to at least weekly (versus 7.7% of the control group). Furthermore, a greater percentage of E (6.8% vs. 2.2%) reported that from a few times a month to at least weekly they felt that it seemed as though everything around was not real. In E, the feeling of recognition raised fright (22.3% vs. 13.2%) and a sense of oppression (19.4% vs. 9.4%). A fifth of E felt recognition during epileptic seizures.ConclusionOnly E regardless of aetiology firmly answered that they had the feeling of recognition during an epileptic seizure; thus question 14 of the I‐IDEA test part 2 discriminated E from C. Paranormal activity, remembering dreams and travel frequency were mostly correlated to DV in E suggesting that the visual–memory network might be involved in epileptic DV.

Background and purpose The purpose of this study was to determine whether switching from branded levetiracetam (Keppra ® ) to a levetiracetam generic equivalent product (Matever ® ) in an epilepsy cohort could provide adequate results in terms of seizure control and tolerability. Methods To be eligible for the study, patients had to have been taking Keppra ® as monotherapy or polytherapy for at least 6 months. Between March 2013 and April 2017, patients were invited to switch to Matever ® as part of their follow‐up. We evaluated the number of seizures per month, drug‐related adverse events and electroencephalography before the switch (T0, baseline) and 6 months after switching (T1). Furthermore, we reported the long‐term follow‐up of patients who continued to use Matever ® after the end of the study, considering the most recent visit for each patient (T2). Results A total of 55 patients refused the switch. Among the remaining 125 patients, 59 (47%) were treated using Keppra ® as monotherapy and 66 (53%) were on Keppra ® as polytherapy. All 125 patients were subjected to switching from Keppra ® to Matever ® . Comparing patients before (T0) and after (T1) switching, we found no statistically significant differences in terms of seizure frequency and occurrence of adverse effects. There were no significant differences (number of seizures/month and drug‐related adverse events) between patients treated with Matever ® as monotherapy and patients who refused the switch and continued to use Keppra ® as monotherapy for a long‐term follow‐up of 48 months. Electroencephalography findings were also unchanged. Conclusion In our sample, brand‐to‐generic levetiracetam switching was effective and safe in both monotherapy and polytherapy regardless of the epilepsy syndrome.

European Journal of NeurologyVolume 24, Issue 12 p. e87-e88 Letter to the Editor Gerstmann–Straussler–Scheinker disease with PRNP P102L heterozygous mutation presenting as progressive myoclonus epilepsy L. Mumoli, L. Mumoli Institute of Neurology, University Magna Græcia, Catanzaro, ItalySearch for more papers by this authorA. Labate, A. Labate orcid.org/0000-0002-8827-7324 Institute of Neurology, University Magna Græcia, Catanzaro, Italy Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, ItalySearch for more papers by this authorA. Gambardella, Corresponding Author A. Gambardella a.gambardella@unicz.it orcid.org/0000-0001-7384-3074 Institute of Neurology, University Magna Græcia, Catanzaro, Italy Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy Correspondence: A. Gambardella, Institute of Neurology, Department of Medical and Surgical Sciences, University Magna Graecia, Germaneto, 88100 Catanzaro, Italy (tel.: +39 0961 3647270; fax: +39 0961 3647177; e-mail: a.gambardella@unicz.it).Search for more papers by this author L. Mumoli, L. Mumoli Institute of Neurology, University Magna Græcia, Catanzaro, ItalySearch for more papers by this authorA. Labate, A. Labate orcid.org/0000-0002-8827-7324 Institute of Neurology, University Magna Græcia, Catanzaro, Italy Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, ItalySearch for more papers by this authorA. Gambardella, Corresponding Author A. Gambardella a.gambardella@unicz.it orcid.org/0000-0001-7384-3074 Institute of Neurology, University Magna Græcia, Catanzaro, Italy Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy Correspondence: A. Gambardella, Institute of Neurology, Department of Medical and Surgical Sciences, University Magna Graecia, Germaneto, 88100 Catanzaro, Italy (tel.: +39 0961 3647270; fax: +39 0961 3647177; e-mail: a.gambardella@unicz.it).Search for more papers by this author First published: 17 November 2017 https://doi.org/10.1111/ene.13447Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume24, Issue12December 2017Pages e87-e88 RelatedInformation

OBJECTIVE:DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD.METHODS:This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT.RESULTS:Rest tremor amplitude was higher in PD patients than in rDIP patients (p < 0.001), while frequency and burst duration were higher in rDIP than in PD (p < 0.001, p < 0.003, respectively). Resting tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p < 0.001). DAT-SPECT was normal in rDIP patients while it was markedly abnormal in patients with PD.CONCLUSIONS:In the absence of DAT-SPECT, the pattern of resting tremor can be considered a useful investigation for differentiating rDIP from PD.

Background and purposeTo evaluate if an automatic magnetic resonance imaging (MRI) processing system may improve detection of hippocampal sclerosis (Hs) in patients with mesial temporal lobe epilepsy (MTLE).MethodsEighty consecutive patients with a diagnosis of MTLE and 20 age- and sex-matched controls were prospectively recruited and included in our study. The entire group had 3-T MRI visual assessment of Hs analysed by two blinded imaging epilepsy experts. Logistic regression was used to evaluate the performances of neuroradiologists and multimodal analysis.ResultsThe multimodal automated tool gave no evidence of Hs in all 20 controls and classified the 80 MTLE patients as follows: normal MRI (54/80), left Hs (14/80), right Hs (11/80) and bilateral Hs (1/80). Of note, this multimodal automated tool was always concordant with the side of MTLE, as determined by a comprehensive electroclinical evaluation. In comparison with standard visual assessment, the multimodal automated tool resolved five ambiguous cases, being able to lateralize Hs in four patients and detecting one case of bilateral Hs. Moreover, comparing the performances of the three logistic regression models, the multimodal approach overcame performances obtained with a single image modality for both the hemispheres, reaching a global accuracy value of 0.97 for the right and 0.98 for the left hemisphere.ConclusionsMultimodal quantitative automated MRI is a reliable and useful tool to depict and lateralize Hs in patients with MTLE, and may help to lateralize the side of MTLE especially in subtle and uncertain cases.

To the Editors: We read with great interest the study by Maccotta et al., titled “Beyond the CA1 subfield: local hippocampal shape changes in MRI-negative temporal lobe epilepsy,” showing that there were local hippocampal shape changes in patients with refractory temporal lobe epilepsy (TLE) without signs of hippocampal atrophy on magnetic resonance imaging (MRI negative). In these patients, indeed, they found primarily hippocampal changes in subicular and hilar/dentate subfields, instead of the significant contraction in all hippocampal subregions, especially CA1 seen in patients with MRI evidence of hippocampal sclerosis (MRI positive). These findings led the authors to hypothesize that the selective involvement of subiculum and parasubiculum may be indicative of seizure propagation to the hippocampal formation (Hf) from the temporal neocortex. In this way, as addressed by Maccotta et al., such local changes depicted by these new computational anatomic techniques may have value in differentiating mesial TLE (mTLE) from lateral TLE. In a recent study aimed at assessing Hf volume and shape characteristics in patients with mTLE with or without MRI evidence of hippocampal sclerosis (Hs), we found hippocampal damage localized to the CA1 and subiculum even in mTLE patients with no evidence of atrophy or Hs that always coincided with the epileptogenic area. Intriguingly, the entity of Hf atrophy in our mTLE-negative patients was less severe and more limited than that depicted in the MRI-positive mTLE group. Moreover, the severity of damage seen on imaging study correlated with a higher risk of seizure refractoriness, even though patients with drug-responsive mTLE also showed similar volume and shape abnormalities, albeit at a lower threshold. In accordance with our findings, a recent longitudinal study showed a progressive atrophy in CA1 sector in mTLE patients with or without Hs, supporting not only the concept of pathologic continuum between these subgroups but the pathogenic role of CA1 subfield in mTLE. Overall, we agree with the authors that the pattern of Hf atrophy, as detected through these new computational anatomic techniques, represents an important step for physicians not only to strengthen the diagnosis, but also to influence and address the clinical management of TLE. These advanced structural MRI approaches may become very useful, especially in patients with TLE with apparent negative standard MRI to better discriminate mTLE from lateral TLE. Moreover, these techniques may reveal even stronger relationships of disease intensity and burden with local hippocampal changes, with consequently more appropriate and effective approaches for its diagnosis and treatment. Obviously, further studies are needed to better corroborate the role of these sophisticated quantitative MRI measures in patients with TLE.

Objective : We used permutation entropy (PE) to disclose abnormalities of cerebral activity in patients with early genetic or sporadic Creutzfeldt-Jakob disease (CJD), as compared to patients with steroid-sensitive subacuteencephalopathies (SSE) and healthy volunteers (HV). Methods : We evaluated 16 EEG of CJD patients, 21 of SSE patients and 33 of HV. EEG of CJD patients were performed at an early stage and didn’t show periodic sharp wave complexes. Diagnosis of SSE was established on clinical and laboratory data. PE was estimated channel by channel. Average PE of all channels and the mean PE values of channels belonging to right and left hemispheres were calculated. The following variables were analysed: age at inclusion, sex, total average PE and mean interhemispheric PE differences. Results : Average PE was significantly lower in CJD patients as compared to HV (mean 0.72, SD 0.03 vs. mean 0.75, SD 0.02, p=0.01). Mean interhemispheric PE difference was higher (mean 0.009, SD 0.006) in CJD patients as compared to both SSE (mean 0.005, SD 0.003) and HV groups (mean 0.004, SD 0.004) (p=0.02). Discussion : The lower average PE value in CJD compared to HV group demonstrates a reduction of EEG complexity that suggests disruption of thalamo-cortical connection since the early phases of disease. Moreover, subjects with CJD showed a significant interhemispheric asymmetry in PE values, indicating that the pathological process of CJD may be initially asymmetric. This study confirms that PE may represent a useful tool to reveal abnormalities of cerebral electric activity not revealed by conventional EEG recordings.