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To assess if the amplitude of the N20 wave (N20Amp) of somatosensory evoked potentials (SSEPs) changes between 12-24 h and 72 h from the return of spontaneous circulation (ROSC) after cardiac arrest and if an N20Amp decrease predicts poor neurological outcome (CPC 3-5) at six months.Retrospective analysis of the ProNeCA multicentre prognostication study dataset. (NCT03849911).In adult comatose cardiac arrest survivors whose SSEPs were recorded at both 12-24 h and 72 h after ROSC, we measured the median N20Amp at each timepoint and the individual change in N20Amp across the two timepoints. We identified their cutoffs for predicting poor outcome with 0% false positive rate (FPR) and compared their sensitivities.We included 236 patients. The median [IQR] N20Amp increased from 1.90 [0.78-4.22] µV to 2.86 [1.52-5.10] µV between 12-24 h and 72 h (p = 0.0019). The N20Amp cutoff for 0% FPR increased from 0.6 µV at 12-24 h to 1.23 µV at 72 h, and its sensitivity increased from 56[48-64]% to 71[63-77]%. Between 12-24 h and 72 h, an N20Amp decrease 53% predicted poor outcome with 0[0-5]% FPR and 26[19-35]% sensitivity. Its combination with an N20Amp 1.23 µV at 72 h increased sensitivity by 1% to 72[64-79]%.In comatose cardiac arrest survivors, the median N20Amp and its cutoff for predicting poor neurological outcome increase between 12-24 and 72 h after ROSC. An N20Amp decrease greater than 53% between these two timepoints predicts poor outcome with 0% FPR, confirming the unfavourable prognostic signal of a low N20Amp at 72 h.

Pseudohypoparathyroidism type 1A (PHP1A) is usually diagnosed in childhood or early adulthood. We describe the case of a 64-year-old woman admitted to the Neurological Unit for recurrent episodes of loss of consciousness and seizures. Glycemia and ECG were normal, while hypocalcemia was noted. Clinical history revealed carpo-pedal spasm since the age of 30 years, cognitive impairment, hypothyroidism since early adulthood, and menopause at 30 years. She was taking oral calcium and cholecalciferol for chronic hypocalcemia. Physical features suggested Albright’s osteodystrophy. Blood calcium was confirmed low, with increased parathyroid hormone, moderate 25OH-vitamin D deficiency, and normal creatinine. Brain CT scan revealed calcifications of the basal ganglia, cortical and subcortical white matter, and cerebellum. Therapy was switched to oral calcitriol, with normalization of calcium levels; levetiracetam was started and no further seizures occurred. The clinical diagnosis of PHP1A was confirmed by molecular analysis, which demonstrated the heterozygous c.568_571del mutation of the GNAS gene. Our report illustrates the natural history of a patient with PHP1A, which went undiagnosed until the age of 64 years, with multi-hormonal resistance and clinical sequelae evolving throughout life, and underlines the importance of diagnosing this rare disease, which has a great impact on patients and their family life.

Purpose to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE). Methods a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6 h after BRV administration. Results 56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100 mg (range 50−300 mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6 h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39–202; p = 0.002). No severe treatment emergent adverse events were observed. Conclusion BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.

Aim To assess if, in comatose resuscitated patients, the amplitude of the N20 wave (N20amp) of somatosensory evoked potentials (SSEP) can predict 6-months neurological outcome. Setting Multicentre study in 13 Italian intensive care units. Methods The N20amp in microvolts (μV) was measured at 12 h, 24 h, and 72 h from cardiac arrest, along with pupillary reflex (PLR) and a 30-min EEG classified according to the ACNS terminology. Sensitivity and false positive rate (FPR) of N20amp alone or in combination were calculated. Results 403 patients (age 69[58–68] years) were included. At 12 h, an N20amp >3 μV predicted good neurological outcome (Cerebral Performance Categories [CPC] 1–2) with 61[50−72]% sensitivity and 11[6–18]% FPR. Combining it with a benign (continuous or nearly continuous) EEG increased sensitivity to 91[82−96]%. For poor outcome (CPC 3–5), an N20Amp ≤0.38 μV, ≤0.73 μV and ≤1.01 μV at 12 h, 24 h, and 72 h, respectively, had 0% FPR with sensitivity ranging from 61[51−69]% and 82[76−88]%. Sensitivity was higher than that of a bilaterally absent N20 at all time points. At 12 h and 24 h, a highly malignant (suppression or burst-suppression) EEG and bilaterally absent PLR achieved 0% FPR only when combined with SSEP. A combination of all three predictors yielded a 0[0−4]% FPR, with maximum sensitivity of 44[36−53]%. Conclusion At 12 h from arrest, a high N20Amp predicts good outcome with high sensitivity, especially when combined with benign EEG. At 12 h and 24 h from arrest a low-voltage N20amp has a high sensitivity and is more specific than EEG or PLR for predicting poor outcome.

Objective This research was focused on expert professionals in epilepsy care to understand their points of view on the care pathway and their living relationships with patients. Methods Researchers prepared a semi-structured parallel chart and distributed it online among 21 Italian centres of care. Each health professional was prompted to write five narratives on cases of patients with epilepsy, subsequently analysed through narrative medicine methods. Next, a consensus meeting was held, to individualise an action plan based on the narratives. Results Ninety-one parallel charts were collected from 25 epileptologists, who had a mean age of 50 years; their narratives concerned patients with a mean age of 37 years, with different types of epilepsy (53 % drug-resistant; 31 % unemployed). The limitations in the daily life of people with epilepsy (57 %), employment (42 %), caregiver burden (51 %), and the universal prevalence of fear were the primary topics that emerged. Attentive and reassuring care relationships were found to be the main element of coping (21 %). A new multi-factorial classification of epilepsies, integrating clinical with social and legal risk factors, was the main agreed action to face the issues identified. Conclusions The narrative medicine approach supplied a broader scenario of living with epilepsy, including the family and social impact and possible effects on the choices for care pathways. The epileptologists showed a strong motivation to care for patients with epilepsy and deep involvement in the care relationships; the use of parallel chart demonstrated to be an effective tool to preserve their wellbeing.

BACKGROUND Bilaterally absent pupillary light reflexes (PLR) or N20 waves of short-latency evoked potentials (SSEPs) are recommended by the 2015 ERC-ESICM guidelines as robust, first-line predictors of poor neurological outcome after cardiac arrest. However, recent evidence shows that the false positive rates (FPRs) of these tests may be higher than previously reported. We investigated if testing accuracy is improved when combining PLR/SSEPs with malignant electroencephalogram (EEG), oedema on brain computed tomography (CT), or early status myoclonus (SM). METHODS Post-hoc analysis of ProNeCA multicentre prognostication study. We compared the prognostic accuracy of the ERC-ESICM prognostication strategy vs. that of a new strategy combining ≥2 abnormal results from any of PLR, SSEPs, EEG, CT and SM. We also investigated if using alternative classifications for abnormal SSEPs (absent-pathological vs. bilaterally-absent N20) or malignant EEG (ACNS-defined suppression or burst-suppression vs. unreactive burst-suppression or status epilepticus) improved test sensitivity. RESULTS We assessed 210 adult comatose resuscitated patients of whom 164 (78%) had poor neurological outcome (CPC 3-5) at six months. FPRs and sensitivities of the ≥2 abnormal test strategy vs. the ERC-ESICM algorithm were 0[0-8]% vs. 7 [1-18]% and 49[41-57]% vs. 63[56-71]%, respectively (p

During epidemic outbreaks, epilepsy course can be modified by different physical and psychological stressors and, most importantly, by irregular therapy intake. The effect of COVID-19 and quarantine isolation on the course of epilepsy and on incidence of new-onset seizures is still unclear. With the aim of managing epilepsy in quarantined patients, three Italian Epilepsy Centers set up telephone consultations using a semistructured interview, allowing a prospective collection of data on seizure course and other seizure-related problems during pandemic. The collected data on seizure course were compared with the analogous period of 2019. The level of patients' concern relating to the COVID-19 pandemic was also assessed using a numeric rating scale. To address the effect of COVID-19 pandemic on seizure incidence, data collection included the number of consultations for first seizures, relapse seizures, and status epilepticus (SE) in the emergency department of one of the participating centers. Clinical telephone interviews suggest the absence of quarantine effect on epilepsy course in our cohort. No differences in incidence of emergency consultations for seizures over a two-month period were also observed compared with a control period. As demonstrated in other infective outbreaks, good antiepileptic drug (AED) supplying, precise information, and reassurance are the most important factors in chronic conditions to minimize psychological and physical stress, and to avoid unplanned treatment interruptions., Highlights • The effect of COVID-19 and quarantine isolation on the course of epilepsy is still unclear. • Epilepsy course during COVID-19 pandemic was assessed through telephone consultations. • COVID-19 pandemic did not change seizure incidence and prevalence in our patient cohort. • In pandemic situations, telemedicine can be a useful tool for epilepsy care.

Bilateral absence of N20 peak in median nerve Somatosensory Evoked Potentials (SSEPs) is considered the most valid predictor of poor outcome in comatose survivors after cardiopulmonary resuscitation. We investigated the consistency in interpreting SSEP recordings in a multicentre study.44 SSEP recordings randomly extracted from 600 recordings of 392 patients included in the "Prognostication of Neurological outcome after Cardiac Arrest (ProNeCa) study" were blindly read by three expert neurophysiologists. Agreement between raters, and individual agreement of each rater vs. reference standard (RS), were calculated using Kappa Coefficients. Inter-rater reliability was calculated with Intra-class Correlation Coefficient (ICC).When raters had to evaluate the presence of N20 with normal amplitude, the inter-rater agreement was very high (Kappa = 0.84). In the case of N20 absence the agreement was good (Kappa = 0.66), but when N20 amplitude was low, the agreement decreased to moderate (Kappa = 0.579) becoming even weaker when it was "Non Assessable" (Kappa = 0.107). The agreement of each rater with the RS had a range from moderate to very good; rater1 Kappa = 0.589 (95%CI 0.397-0.781; p 0.001), rater2 Kappa = 0.644 (95%CI 0.460-0.828; p 0.001), rater3 Kappa = 0.859 (95%CI 0.698-1.000; p 0.001). The ICC was barely good, 0.682 (95%CI 0.539-0.798; p = 0.0075).Different health professionals, using different equipment in a multicentre study, had very good inter-rater agreement in interpreting SSEP records. The interpretation of "Non Assessable" SEPPs, mainly in relation to noise level, is still a crucial issue because it increases rater uncertainty. For this reason, it is important to focus on improving recording quality and interpretation of records.

Aims To assess the accuracy of electroencephalogram (EEG) and somatosensory evoked potentials (SEPs) recorded at 12 and 72 h from resuscitation for predicting six-months neurological outcome in patients who are comatose after cardiac arrest. Methods Prospective multicentre prognostication study. EEG was classified according to the American Clinical Neurophysiology Society terminology. SEPs were graded according to the presence and amplitude of their cortical responses. Neurological outcome was defined as good (cerebral performance categories [CPC] 1–3) vs. poor (CPC 4–5). None of the patients underwent withdrawal of life-sustaining treatment. Results A total of 351 patients were included, of whom 134 (38%) had good neurological outcome. At 12 h, a continuous, nearly continuous and low-voltage EEG pattern predicted good neurological outcome with 71[61–80]% sensitivity, while an isoelectric EEG and a bilaterally absent/absent-pathological amplitude (AA/AP) cortical SEP pattern predicted poor neurological outcome with 14[8–21]% and 59[50–68]% sensitivity, respectively. Specificity was 100[97–100]% for all predictors. At 72 h, both an isoelectric, suppression or burst-suppression pattern on EEG and an AA/AP SEP pattern predicted poor outcome with 100[97–100]% specificity. Their sensitivities were 63[55–70]% and 66[58–74]%, respectively. When EEG and SEPs were combined, sensitivity for poor outcome prediction increased to 79%. Conclusions In comatose resuscitated patients, EEG and SEPs predicted good and poor neurological outcome respectively, with 100% specificity as early as 12 h after cardiac arrest. At 72 h after arrest, unfavourable EEG and SEP patterns predicted poor neurological outcome with 100% specificity and high sensitivity, which further increased after their combination.

The data presented here are related to our research article entitled “Neurophysiology and neuroimaging accurately predict poor neurological outcome within 24 hours after cardiac arrest: a prospective multicentre prognostication study (ProNeCA)” [1].We report a secondary analysis on the ability of somatosensory evoked potentials (SEPs), brain computed tomography (CT) and electroencephalography (EEG) to predict poor neurological outcome at 6 months in 346 patients who were comatose after cardiac arrest. Differently from the related research article, here we included cerebral performance category (CPC) 3 among poor outcomes, so that the outcomes are dichotomised as CPC 1–2 (absent to mild neurological disability: good outcome) vs. CPC 3–5 (severe neurological disability, persistent vegetative state, or death: poor outcome). The accuracy of the index tests was recalculated accordingly. A bilaterally absent/absent-pathological amplitude (AA/AP) N20 SEPs wave, a Grey Matter/White Matter (GM/WM) ratio

Aim: Hypoxic-ischemic-encephalopathy is a severe and frequent neurological complication of successful cardiopulmonary-resuscitation after cardiac arrest. Prognosticating neurological outcomes in patients with hypoxic-ischemic-encephalopathy is challenging and recent guidelines suggest a multimodal approach. Only few studies have analyzed the prognostic power of the association between instrumental tests and, in addition, most of them were monocentric, retrospective and evaluating only poor outcome. Methods/design: We designed a multicenter prospective cohort study to assessing the prognostic power of the association of electroencephalogram and somatosensory evoked potentials for the prediction of both poor and good neurological outcomes at different times after cardiac arrest. Discussion: The results of our study will provide a high level of evidence for the use of neurophysiological evaluation in the current clinical practice.

SEPs are reliable predictor of poor outcome in comatose patients after cardiac arrest (CA). Recently also the role of EEG has been reassessed. To evaluate the prognostic value of EEG and SEPs association in post-anoxic coma at different recording time. We included comatose patients after CA. EEG and SEPs were recorded within 12 hs and at 72 hs after CA. EEG was classified into grade 1(“continuous”/“nearly-continuous”) and grade 2(discontinuous/burst-suppression/suppression/isoelectric). SEPs were dichotomized into “bilaterally absent” (BA) and “present”. Outcome was evaluated at 6 months by GOS. “Recovery of consciousness” was considered good outcome. Ten centers took part to the study and 282 patients were included. EEG and SEPs were recorded in 141 within 12 hs in 162 at 72 hs. Grade 1 EEG at 12 hs always predicted good outcome, grade 2 pattern at 72 hs predicted poor outcome with higher predictive power. BA SEPs always predicted poor outcome. Grade 1 EEG was always associated with present SEPs. EEG is a reliable time-dependent predictor of good outcome (within 12 h) and poor outcome (after 72 h). SEP is time-independent predictor of poor outcome. Early grade 1 EEG is never associated with BA SEP. Early association recordings of EEG and SEPs increase of the reliability of prognosis prediction in post-anoxic coma.

Background:Ifosfamide (IFX), an alkylating agent and isomer of cyclophosphamide, is used as a single agent or a component of multi-agent chemotherapy in the treatment of ovarian, testicular, head and neck cancers, sarcomas and lymphomas. Encephalopathy is manifested by cerebellar ataxia, confusional state, complex visual hallucinations, extrapyramidal signs, seizures, and mutism.Case reports:We report two patients with non-Hodgkin’s lymphoma presenting with mutism and confusional state after IFX infusion. Nonconvulsive status epilepticus (NCSE) as the cause of confusion was diagnosed on the basis of EEG pattern and the apparent improvement following intravenous administration of diazepam.Conclusions:Electroencephalogram abnormalities during IFX treatment have been described but recordings are only available in six cases. In three of them, paroxysmal alterations warranted the diagnosis of NCSE; however, most cases of IFX encephalopathy might have associated NCSE.

Somatosensory evoked potentials(SEPs) and EEG are reliable outcome predictors of coma after cardiac arrest (CA). Nevertheless, only few multicentric studies are available. Aim of the study was to evaluate the prognostic value of EEG and SEPs association in post-anoxic comatose patients at different recording time from cardiac arrest (CA) in an Italian multicentric study. Comatose patients after CA treated with TH were included. EEG and SEPs were recorded within 12 h and at 72 h after CA. EEG was classified into “non-continuous” and “continuous”. SEPs were dichotomized into “bilaterally absent” (BA) and “present”. Neurologic outcome was evaluated at 6 months by GOS: “awakening”(GOS 3–5) was considered good outcome. 83 patients were included to date. “Continuous” EEG pattern at 12 h always predicted good outcome, “non-continuous” pattern at 72 h always predicted poor outcome. BA SEPs always predicted poor outcome. Early “continuous” EEG pattern was always associated with present SEPs. SEPs provide a specific and time-independent predictor of poor outcome. EEG provide a specific and time-dependent predictor of good outcome (at

The prediction of neurologic outcome in comatose patients after cardiac arrest (CA) has been investigated and the findings were summarized in a practice parameter of the American Academy of Neurology (1). These guidelines did not include the EEG as a reliable outcome indicator but recent studies on continuous EEG recorded during TH have re-evaluated the role of EEG (2–4). These studies underline the utility of a simplified classification system of EEG patterns and point to which pattern attains reliable predictive value both for good and bad outcomes. These reports are of high clinical relevance because, until today, the possibility of identifying early prognostic indicators of good outcome in patients surviving to CA has not been investigated. At the best of our knowledge, only few multicentre prospective studies (4–6) analyzed the prognostic value of EEG and SEP recorded in the same patient after CA as single predictor but none analyzed the diagnostic accuracy of the association of these two tests. We present the study protocol of Italian Multicentre Study about prognostic value of EEG and SEP in comatose patients after CA (ProNeCA) proposed by study group of “Intraoperative and Intensive Care Clinical Neurophysiology” of the Italian Society of Clinical Neurophysiology.

Some evidence would indicate that a serotonergic deficit may be involved in epileptogenesis. A preliminary trial of citalopram, a selective inhibitor of serotonin reuptake, was carried out. Citalopram 20mg/day was given to 11 non-depressed patients with poorly controlled epilepsy as an add on treatment with an open label design for 8–10 months. The median seizure frequency dropped by 55.6% in the whole group, with nine patients improving by at least 50%. No adverse reactions occurred with the exception of mild drowsiness. There were no changes of post-treatment as compared to pre-treatment AED serum concentrations. Although controlled studies are required to confirm the anticonvulsant effect of citalopram, these findings may be regarded as an indirect evidence of serotonergic impairment in human epileptogenesis.

The density of the serotonin transporter in the plasma membranes of blood platelets was evaluated by labelled paroxetine binding in three different groups. These groups were: normal controls, epileptic patients having undergone a recent seizure (less than 4 days before) and patients who equally recently presented psychogenic non-epileptic seizures (pseudoseizures). Real seizures resulted in a significant decrease of membrane serotonin transporter density. In the instances of pseudoseizures, its membrane density was undistinguishable from that of normal controls. These data lend further support to the idea that down regulation of serotonin transporter may play a homeostatic role in the cessation of epileptic seizures.

Serotonin transporter (SERT) was studied by [3H]-paroxetine binding in blood platelets from controls and epileptic patients with generalized convulsive seizures. The average KD and BMax were not different in the two cases. However, a significant decrease was found in the serotonin transporter density in the platelet membranes from patients having undergone an epileptic seizure less than 4 days before. This circumstance may indicate a homeostatic reaction to the epileptic attack.

Cephalosporins may induce nonconvulsive status epilepticus (NCSE), a potentially reversible condition. Despite the wide use of these antibiotics, there are only few reported cases, because this condition is probably underestimated. We report two new cases of NCSE occurring during treatment with cefepime and ceftazidime, and emphasize the utility of emergent electroencephalogram in patients with an acute altered state of consciousness while receiving treatment with cephalosporins, particularly when there is evidence of impaired renal function.