The academic point-of-care anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel (ARI-0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma.

Varnimcabtagene autoleucel (var-cel) is an academic anti-CD19 chimeric antigen receptor (CAR) product used for the treatment of non-Hodgkin lymphoma (NHL) in the CART19-BE-01 trial. Here we report updated outcomes of patients with NHL treated with var-cel. B-cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL). Forty-five patients with NHL were treated. Cytokine release syndrome (any grade) occurred in 84% of patients (4% grade ≥3) and neurotoxicity in 7% (2% grade ≥3). The objective response rate was 73% at Day +100, and the 3-year duration of response was 56%. The 3-year progression-free and overall survival were 40% and 52% respectively. High lactate dehydrogenase was the only covariate with an impact on progression-free survival. The 3-year incidence of B-cell recovery was lower in patients with NHL compared to ALL (25% vs. 60%). In conclusion, in patients with NHL, the toxicity of var-cel was manageable, while B-cell recovery was significantly prolonged compared to ALL. This trial was registered as NCT03144583.

A low total metabolic tumor volume independently predicts for a longer time to first treatment in initially observed, low tumor burden follicular lymphoma.

Watchful waiting is an acceptable management strategy for advanced-stage, low tumor burden (LTB) patients with follicular lymphoma (FL). However, the prediction of how long this treatment-free observation period will last remains imperfect. We explored whether total metabolic tumor volume (TMTV) and other positron emission tomography parameters were predictive of time to first treatment (TTFT). We analyzed 97 grade 1-3A advanced-stage LTB FL patients and found that a high TMTV was associated with other tumor burden features at diagnosis. Patients with a TMTV above our established cutoff of 50 mL had a significantly shorter median duration of observation (2.6 vs. 8.8 years; p = 0.001). At 5 years, 77% of patients with a high TMTV and 46% of patients with a low TMTV required treatment. In the multivariable analysis, a high TMTV was the only independent factor predicting TTFT (hazard ratio = 2.09; p = 0.017). Overall, TMTV is a strong predictor of the duration of observation in LTB FL patients. Upon validation of our cutoff in external series and standardization of the methodology, the TMTV could become an additional factor to consider deferring or initiating treatment in otherwise LTB patients.

Psychiatric and psychological assessment of Spanish patients with drug-resistant epilepsy and psychogenic nonepileptic seizures (PNES) with no response to previous treatments.

OBJECTIVE: Psychogenic nonepileptic seizures (PNES) are common imitators of epileptic seizures. Refractoriness to antiseizure medication hinders the differential diagnosis between ES and PNES, carrying deleterious consequences in patients with PNES. Psychiatric and psychological characteristics may assist in the differential diagnosis between drug-resistant epilepsy (DRE) and PNES. Nevertheless, current comprehensive psychiatric and psychological descriptive studies on both patient groups are scarce and with several study limitations. This study provides a comprehensive psychiatric and psychological characterization of Spanish patients with DRE and PNES. METHOD: A cross-sectional and comparative study was completed with 104 patients with DRE and 21 with PNES. Psychiatric and psychological characteristics were assessed with the HADS, SCL-90-R, NEO-FFI-R, PDQ-4+, COPE, and QOLIE-31 tests. Parametric and non-parametric tests were used, and regression models were fit to further explore factors affecting patients' life quality. RESULTS: Patients with PNES had greater levels of somatization and extraversion and were associated with benzodiazepine intake. Patients with DRE showed greater narcissistic personality disorder symptoms than those with PNES. In patients with DRE, difficulty in performing basic needs-related tasks and greater psychological distress severity and seizure frequency were associated with poorer life quality. In contrast, being a woman, having a psychiatric disorder history, and greater psychiatric symptoms' intensity were associated with poorer life quality in patients with PNES. CONCLUSION: Patients with DRE and PNES share similar psychiatric and psychological characteristics, with only very few being significantly different.

Results of ARI-0001 CART19 cell therapy in patients with relapsed/refractory CD19-positive acute lymphoblastic leukemia with isolated extramedullary disease.

We evaluated outcomes of 18 patients with isolated extramedullary disease (iEMD) relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with the CD19-directed CAR T cells ARI-0001 in two centers (adult and pediatric), including patients treated in the CART19-BE-01 trial and the consecutive compassionate use program. iEMD was detected by PET-CT in 78% (14/18), and/or by cerebrospinal fluid analysis in 28% (5/18). Patients received cyclophosphamide and fludarabine followed by 1 × 106 ARI-0001 cells/kg, initially as a single dose (first patient) and later split into three fractions (10%, 30%, and 60%). Cytokine release syndrome (CRS) occurred in 50% (9/18) of patients, with no cases of grade ≥3 CRS, and 1 case (6%) of grade 1 neurotoxicity. Tocilizumab was used in 6% of patients (1/18). Procedure-related mortality was 0% at 2 years. Objective responses were seen in 94% (95% confidence interval [CI]: 73%-99%) of patients, with complete responses (CR) seen in 78% (95% CI: 52%-94%) of them. Progression-free and overall survival were 49% (95% CI: 30%-79%) and 61% (95% CI: 40%-92%) at 2 years. In conclusion, the use of ARI-0001 cells in patients with R/R ALL and iEMD was associated with a safety and efficacy profile that is comparable with what is observed in patients with marrow involvement and in line with other CART19 products.

Psychiatric disorders in patients with resistant temporal lobe epilepsy two years after undergoing elective surgery. A longitudinal study.

PURPOSE: Psychiatric morbidity in temporal lobe epilepsy (TLE) is frequent and negatively affects patients' life quality. Surgery is the procedure of choice when treating seizures, although the effects on psychiatric disorders remain unclear. We evaluate the effect of surgery on psychiatric disorders in patients with TLE two years after the intervention, to then shed light on how these are related to anxiety and depression symptoms, and Interictal Dysphoric Disorder (IDD). METHODS: We included data from 65 patients with TLE whose psychiatric evaluations were performed according to DSM-IV criteria. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) test. RESULTS: At 2-year follow-up, anxiety and depressive disorders decreased, and psychotic disorders augmented without statistical significance. Baseline psychiatric disorders predisposed to psychiatric pathology at 2-year follow-up and did not correlate with epilepsy outcome after surgery. Postoperative psychiatric disorders correlated with the seizure incidence two years after the intervention, suggesting that epilepsy and psychiatric disorders were associated in processes such as surgery. De novo psychiatric disorders represented 52% of postoperative psychiatric pathology, 62% being psychotic disorders. De novo psychiatric disorders became more frequent from the first year of surgery, occurring mainly in patients free of seizures. The HADS test scores and IDD correlated with psychiatric disorders at 2-year follow-up. CONCLUSIONS: Baseline psychiatric disorders did not influence surgery outcome, but correlated with psychiatric disorders' prevalence two years after surgery. Despite not finding statistical significance, surgery reduced the prevalence of psychiatric disorders, and de novo psychiatric disorders were associated with an improvement in the epilepsy course at 2-year follow-up.

Beyond the Epileptic Focus: Functional Epileptic Networks in Focal Epilepsy.

Focal epilepsy can be conceptualized as a network disorder, and the functional epileptic network can be described as a complex system of multiple brain areas that interact dynamically to generate epileptic activity. However, we still do not fully understand the functional architecture of epileptic networks. We studied a cohort of 21 patients with extratemporal focal epilepsy. We used independent component analysis of functional magnetic resonance imaging (fMRI) data. In order to identify the epilepsy-related components, we examined the general linear model-derived electroencephalography-fMRI (EEG-fMRI) time courses associated with interictal epileptic activity as intrinsic hemodynamic epileptic biomarkers. Independent component analysis revealed components related to the epileptic time courses in all 21 patients. Each epilepsy-related component described a network of spatially distributed brain areas that corresponded to the specific epileptic network in each patient. We also provided evidence for the interaction between the epileptic activity generated at the epileptic network and the physiological resting state networks. Our findings suggest that independent component analysis, guided by EEG-fMRI epileptic time courses, have the potential to define the functional architecture of the epileptic network in a noninvasive way. These data could be useful in planning invasive EEG electrode placement, guiding surgical resections, and more effective therapeutic interventions.

Life expectancy of follicular lymphoma patients in complete response at 30 months is similar to that of the Spanish general population.

The use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression-free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age-matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10-year period who needed therapy and were treated with rituximab-containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10-year overall survival (OS) of 53% and 87% for non-CR30 and CR30 patients, respectively. Ten-year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex- and age-matched Spanish general population.

Unilateral pallidal stimulation for disabling dystonia due to Rasmussen's disease.

OBJECTIVE: To describe an adult patient with Rasmussen's disease with focal dystonia as the most disabling symptom and the good response to unilateral globus pallidus internus (GPi) deep brain stimulation (DBS). METHODS: Retrospective review of clinical records and diagnostic tests. RESULTS: The patient had displayedmild focal seizures with sensory and motor symptoms on the left arm and hemiface since the age of 22. Ten years later she experienced abrupt onset of focal left dystonia involving mainly the leg. Brain MRI showed progressive right hemisphere atrophy, and  18 fluorodeoxyglucose-positron emission tomography (18FDG-PET) showed right hypometabolism mainly over the frontal and insular regions. Brain biopsy confirmed chronic encephalitis. The dystonia became very severe and made walking extremely difficult. Different treatments including dopaminergic, anticholinergic, immunomodulatory drugs and botulinum toxin were ineffective. Finally the patient was treated with unilateral GPi DBS. Shortly after the onset of the stimulation, the dystonia started to improve. Parameters have been adjusted, and 18 months after surgery the patient is able to walk and run unaided, although a mild left leg dystonia persists. CONCLUSION: Rasmussen's disease may be difficult to diagnose in adult patients. Associated movement disorders may be more disabling than seizures. Focal dystonia may be treated successfully with DBS.

PISCOM: a new procedure for epilepsy combining ictal SPECT and interictal PET.

PURPOSE: We present a modified version of the SISCOM procedure that uses interictal PET instead of interictal SPECT for seizure onset zone localization. We called this new nuclear imaging processing technique PISCOM (PET interictal subtracted ictal SPECT coregistered with MRI). METHODS: We retrospectively studied 23 patients (age range 4-61 years) with medically refractory epilepsy who had undergone MRI, ictal SPECT, interictal SPECT and interictal FDG PET and who had been seizure-free for at least 2 years after surgical treatment. FDG PET images were reprocessed (rFDG PET) to assimilate SPECT features for image subtraction. Interictal SPECT and rFDG PET were compared using statistical parametric mapping (SPM). PISCOM and SISCOM images were evaluated visually and using an automated volume of interest-based analysis. The results of the two studies were compared with each other and with the known surgical resection site. RESULTS: SPM showed no significant differences in cortical activity between SPECT and rFDG PET images. PISCOM and SISCOM showed equivalent results in 17 of 23 patients (74%). The seizure onset zone was successfully identified in 19 patients (83%) by PISCOM and in 17 (74%) by SISCOM: in 15 patients (65%) the two techniques showed concordant successful results. The volume of interest-based analysis showed no significant differences between PISCOM and SISCOM in identifying the extension of the seizure onset zone. However, PISCOM showed a lower amount of indeterminate activity due to propagation, background or artefacts. CONCLUSION: Preliminary findings of this initial proof-of-concept study suggest that perfusion and glucose metabolism in the cerebral cortex can be correlated and that PISCOM may be a valid technique for identification of the seizure onset zone. However, further studies are needed to validate these results.

Seizure-onset zone localization by statistical parametric mapping in visually normal (18) F-FDG PET studies.

OBJECTIVE: Neuroimaging is crucial in the presurgical evaluation of patients with medically refractory epilepsy. To improve the moderate sensitivity of [(18) F]fluorodeoxyglucose-positron emission tomography ((18) F-FDG-PET), our aim was to evaluate the usefulness of statistical parametric mapping (SPM) to localize the seizure-onset zone (SOZ) in PET studies deemed normal by visual assessment. METHODS: Fifty-five patients with medically refractory epilepsy whose (18) F-FDG-PET was visually evaluated as normal were retrospectively included. Twenty of these patients had undergone surgical intervention. PET images were analyzed by SPM8 using a corrected p-value of p < 0.05 and three uncorrected p-values of p < 0.0001, p < 0.001, and p < 0.005, matched with minimum cluster sizes of k > 0, k > 20, k > 100, and k > 200, respectively. The SPM-identified potential seizure zone (SZ) was compared to the SOZ, which was determined by consensus during patient management meetings in the epilepsy unit, taking into account presurgical tests. Studies in which the SPM-identified potential SZ was concordant with the SOZ were considered "correctly localizing." RESULTS: The SPM threshold combination with the least restrictive p-value and greatest minimum cluster size achieved the highest rate of correctly localizing studies. When p < 0.005/k > 200 was used, 40% (22/55) of studies were correctly localizing, and the concordance obtained in the surgically intervened subgroup was substantial (к = 0.607, 95% confidence interval [CI] 0.258-0.957), which was comparable to the concordance obtained by magnetic resonance imaging (MRI) (к = 0.783, 95% CI 0.509-1.000). SIGNIFICANCE: SPM offers improved SOZ localization in (18) F-FDG-PET studies that are negative on visual assessment. For this purpose, statistical parametric maps could be thresholded with liberal p-values and restrictive cluster sizes.

A prospective study contrasting the psychiatric outcome in drug-resistant epilepsy between patients who underwent surgery and a control group.

OBJECTIVE: Psychiatric morbidity in drug-resistant epilepsy is frequent and has a negative influence on quality of life. Surgery is proven to be the best therapeutic alternative for treating seizures. However, it is inconclusive with the current evidence whether surgery, per se, is a risk factor or promotes amelioration of psychiatric disorders. Until now, most studies have been cross-sectional with small or heterogeneous groups. In addition, the few prospective studies did not have an identical control group. The present study aims to clarify the role of surgery in psychopathologic alterations. METHODS: We analyzed, through a prospective case-control study, the psychopathologic outcomes of patients with drug-resistant epilepsy, comparing those who underwent surgery and those who continued with pharmacologic treatment due to not being suitable for surgery. The assessments were performed during presurgical evaluation and 6 months after surgery. We studied psychiatric changes for each group, compared differences between groups, and also analyzed de novo and remission cases. Finally, we determined associated factors for postsurgical psychiatric disturbances. RESULTS: The surgical group experienced a significant decrease in psychopathologic alterations in comparison with the control group. In addition, distress perception of surgical patients also improved, whereas it did not decrease in the control group. Patients who underwent surgery presented a decrease in depressive and anxiety symptoms, whereas the nonsurgical group increased its anxiety levels. De novo disturbances that appeared after surgery were less frequent than in nonsurgical patients. We observed significant favorable outcomes considering de novo versus remission cases for anxiety, depression, and total symptoms only in the surgical group. The two main predictors for psychiatric disorders after surgery were presurgical psychiatric functioning and surgery. SIGNIFICANCE: Provides evidence that surgery improves psychiatric functioning in drug-resistant epilepsy through a prospective controlled study.

Prognosis of patients with diffuse large B cell lymphoma not reaching complete response or relapsing after frontline chemotherapy or immunochemotherapy.

A retrospective study was performed to assess the outcome of patients with diffuse large B cell lymphoma (DLBCL) who did not achieve complete response or who relapsed before and after the use of rituximab. Clinical features and outcome of 816 (425 M/391 F; median age 63 years) patients diagnosed from 1991 to 2001 (pre-rituximab era, N = 348) and from 2002 to 2012 (rituximab era, N = 468) in a single institution were evaluated. Five hundred fifty-three patients achieved complete remission (CR), 57 partial response (PR), and 206 were refractory with a median overall survival of 15, 1.5, and 0.4 years, respectively. Patients receiving rituximab had lower risk of refractoriness or relapse. In primarily refractory and PR patients, there was not a difference in survival depending on whether patients received or not rituximab-containing frontline treatment. Early death rate was 11%, including 3.6% due to infectious complications. Rituximab did not modify these figures. In the relapse setting, 5-year survival from relapse was 25% for patients who never received rituximab, 54% for those who received rituximab only at relapse, and 48% for those treated with immunochemotherapy both as frontline and at relapse. In conclusion, relapsed/refractory patients with DLBCL show poor prognosis despite the use of frontline immunochemotherapy. New therapeutic approaches are needed in this group of patients.

Design and validation of a diagnostic suspicion checklist to differentiate epileptic from psychogenic nonepileptic seizures (PNES-DSC).

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) are complex clinical manifestations and misdiagnosis as status epilepticus remains high, entailing deleterious consequences for patients. Video-electroencephalography (vEEG) remains the gold-standard method for diagnosing PNES. However, time and economic constraints limit access to vEEG, and clinicians lack fast and reliable screening tools to assist in the differential diagnosis with epileptic seizures (ES). This study aimed to design and validate the PNES-DSC, a clinically based PNES diagnostic suspicion checklist with adequate sensitivity (Se) and specificity (Sp) to discriminate PNES from ES. METHODS: A cross-sectional study with 125 patients (n = 104 drug-resistant epilepsy; n = 21 PNES) admitted for a vEEG protocolised study of seizures. A preliminary PNES-DSC (16-item) was designed and used by expert raters blinded to the definitive diagnosis to evaluate the seizure video recordings for each patient. Cohen's kappa coefficient, leave-one-out cross-validation (LOOCV) and balance accuracy (BAC) comprised the main validation analysis. RESULTS: The final PNES-DSC is a 6-item checklist that requires only two to be present to confirm the suspicion of PNES. The LOOCV showed 71.4% BAC (Se = 45.2%; Sp = 97.6%) when the expert rater watched one seizure video recording and 83.4% BAC (Se = 69.6%; Sp = 97.2%) when the expert rater watched two seizure video recordings. CONCLUSION: The PNES-DSC is a straightforward checklist with adequate psychometric properties. With an integrative approach and appropriate patient history, the PNES-DSC can assist clinicians in expediting the final diagnosis of PNES when vEEG is limited. The PNES-DSC can also be used in the absence of patients, allowing clinicians to assess seizure recordings from smartphones.

Interim FDG PET/CT as a prognostic factor in diffuse large B-cell lymphoma.

PURPOSE: Interim (18)F-FDG PET performed early during the course of therapy in diffuse large B-cell lymphoma (DLBCL) is a good predictor of outcome. However, interpretation criteria for interim PET for the evaluation of tumour response are still not clearly defined. The study aim was to assess whether interim PET can predict overall survival (OS) and progression-free survival (PFS) in DLBCL patients following three different sets of parameters, two qualitative (visual) methods and one semiquantitative. METHODS: A total of 50 newly diagnosed DLBCL patients were prospectively enrolled in this study. All patients had a PET/CT scan at diagnosis and an interim PET/CT scan after the second or third cycle of chemotherapy. Three methods of evaluation for the interim PET/CT were used: a qualitative three-point scoring (3-PS) method, a qualitative 5-PS method and a semiquantitative method (ΔSUVmax). The degree of correlation between therapy response seen on FDG PET and PFS and OS was determined. RESULTS: The analysis of the visual 3-PS method showed no statistically significant difference in PFS and OS. The estimated 5-year PFS and OS were 79 % and 92 %, respectively, in patients with an interim PET scan showing uptake not greater than in the liver versus 50 % in patients with uptake greater than in the liver, and this difference was statistically significant. The optimal cut-off value of ΔSUVmax that could predict the PFS and OS difference in patients with DLBCL was 76 % (95 % CI 62.7-89.2 %) and 75 % (95 % CI, 54.6-95.4 %), respectively. CONCLUSION: Our results support the use of liver uptake as an indicator in the qualitative evaluation of interim PET, or a ΔSUVmax greater than 75 % in semiquantitative analysis. Interim PET may predict PFS and OS and could be considered in the prognostic evaluation of DLBCL.

Identifying the cortical substrates of interictal epileptiform activity in patients with extratemporal epilepsy: An EEG-fMRI sequential analysis and FDG-PET study.

PURPOSE: The aim of this study was to apply sequential analysis of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) data to study the cortical substrates related to the generation of the interictal epileptiform activity (IEA) in patients with pharmacoresistant extratemporal epilepsy. METHODS: We analyzed fMRI data from 21 children, adolescents, and young adults patients who showed frequent bursts or runs of spikes on EEG, by using the sequential analysis method. We contrasted consecutive fixed-width blocks of 10 s to obtain the relative variations in cerebral activity along the entire fMRI runs. Significant responses (p < 0.05, family-wise error (FWE) corrected), time-related to the IEA recorded on scalp EEG, were considered potential IEA cortical sources. These results were compared with those from the fluorodeoxyglucose-positron emission tomography (FDG-PET), intracranial EEG (two patients), and surgery outcome (eight patients). KEY FINDINGS: The typical IEA was recorded in all patients. After the sequential analysis, at least one significant blood oxygen level-dependent (BOLD) response spatially consistent with the presumed epileptogenic zone was found. These IEA-related activation areas coincided when superimposed with the hypometabolism depicted by the FDG-PET. These data were also consistent with the invasive EEG findings. Epileptic seizures were recorded in eight patients. A subset of IEA-associated fMRI activations was consistent the activations at seizure-onset determined by sequential analysis. The inclusion of the IEA-related areas in the resection rendered the patients seizure-free (five of eight operated patients). SIGNIFICANCE: The EEG-fMRI data sequential analysis could noninvasively identify cortical areas involved in the IEA generation. The spatial relationship of these areas with the cortical metabolic abnormalities depicted by the FDG-PET and their intrinsic relationship regarding the ictal-onset zone could be useful in epilepsy surgery planning.

Positron emission tomography with α-[11C]methyl-L-tryptophan in tuberous sclerosis complex-related epilepsy.

OBJECTIVE: Tuberous sclerosis complex (TSC) is often associated with cerebral tubers and medically intractable epilepsy. We reevaluated whether increased uptake of α-[(11) C]methyl-l-tryptophan (AMT) in cerebral tubers is associated with tuber epileptogenicity. METHODS: We included 12 patients (six male, 4-53 years old) with TSC and refractory seizures who were evaluated for epilepsy surgery in our center, including video-electroencephalographic (EEG) monitoring, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI), and positron emission tomography (PET) with α-[(11) C]methyl-l-tryptophan (AMT-PET). Nine of these 12 patients also underwent intracerebral EEG recording. AMT uptake in each tuber was visually evaluated on PET coregistered with MRI. An AMT uptake index based on lesional/healthy cortex ratio was also calculated. Sensitivity and specificity values of AMT-PET in the detection of epileptogenic lesions were obtained, using the available electroclinical and neuroimaging evidence as the gold standard for epileptogenicity. RESULTS: A total of 126 tubers were identified. Two of 12 patients demonstrated a tuber with clearly increased AMT uptake, one of whom also showed a subtle increased AMT uptake in another contralateral tuber. Four other patients showed only subtle increased AMT uptake. The only two tubers with clearly increased AMT uptake proved to be epileptogenic based on intracerebral EEG data, whereas none of the tubers associated with subtle increased AMT uptake were involved at ictal onset. In a per-patient approach, this yielded a sensitivity of clearly increased AMT uptake in detecting tuber epileptogenicity of 17% (2/12 patients), whereas the per-lesion sensitivity and specificity were 12% (95% confidence interval [CI]: 3-34%) and 100% (95% CI: 97-100%), respectively. SIGNIFICANCE: AMT-PET is a specific neuroimaging technique in the identification of epileptogenic tubers in TSC. Despite its low sensitivity, the clinical usefulness of AMT-PET still deserves to be considered according to the challenging complexity of epilepsy surgery in tuberous sclerosis.

Influence of personality profile in patients with drug-resistant epilepsy on quality of life following surgical treatment: A 1-year follow-up study.

The objectives of this study are to determine the influence of personality profile in patients with drug-resistant epilepsy on quality of life (QoL) after surgical treatment and compare the results with a non-surgical control group at the 1-year follow-up. We conducted a prospective, comparative, controlled study, including 70 patients suffering from drug-resistant epilepsy. Demographic, psychiatric, neurological, and psychological data were recorded at the baseline and at the 1-year follow-up. Assessment of personality dimensions was performed using the NEO-FFI-R questionnaire; severity of anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS), and QoL was evaluated using the QOLIE-31. At the 1-year follow-up, comparing the control and the surgical groups, we detected differences in scores of most items of QoL, which were higher in those patients who had undergone surgery. High levels of Conscientiousness and Openness to experience at the baseline in patients who underwent surgery predicted better post-surgical outcomes in the QoL scores, whereas high neurotic patients showed worse QoL results. Postoperative changes in QoL in patients were associated with the personality profile at the baseline. QoL measures significantly improved in the surgical group compared with the non-surgical group but were not associated with baseline or postoperative seizure frequency at 1 year.

Presurgical evaluation of drug-resistant paediatric focal epilepsy with PISCOM compared to SISCOM and FDG-PET.

PURPOSE: Children with drug-resistant focal epilepsy have a compromised quality of life. Epilepsy surgery can control or significantly reduce the seizures. We assessed and compared the usefulness of PISCOM, a new nuclear imaging processing technique, with SISCOM and 18F-FDG PET (FDG-PET) in pre-surgical evaluation of paediatric drug-resistant focal epilepsy. METHODS: Twenty-two children with pharmcorefractory epilepsy, mainly extratemporal, who had undergone pre-surgical assessment including SISCOM and FDG-PET and with postsurgical favorable outcome (Engel class I or II) for at least two years, were included in this proof-of-concept study. All abnormalities observed in SISCOM, FDG-PET and PISCOM were compared with each other and with the known epileptogenic zone (EZ) based on surgical treatment, histopathologic and surgical outcome results. Global interobserver agreement, Cohen's Kappa coeficient and PABAK statistic were calculated for each technique. RESULTS: PISCOM concordance with the known EZ was significantly higher than SISCOM (p<0.05), and no statistically differences were found with FDG-PET. PISCOM showed successful identification in 19 of 22 cases (86%), successful concordant with FDG-PET in 17 (77%), and SISCOM in 11 (50%). If we consider PISCOM and FDG-PET results together, both techniques successfully localized the known EZ in all cases. The measures of agreement between two experts in nuclear medicine were higher in PISCOM than in SISCOM and FDG-PET. CONCLUSION: PISCOM could provide complementary presurgical information in drug-resistant paediatric focal epilepsy, particularly in cases in which FDG-PET is doubtful or negative, replacing SISCOM and sparing the use of interictal SPECT.

Evaluating the performance of Bayesian and frequentist approaches for longitudinal modeling: application to Alzheimer's disease.

Linear mixed effects (LME) modelling under both frequentist and Bayesian frameworks can be used to study longitudinal trajectories. We studied the performance of both frameworks on different dataset configurations using hippocampal volumes from longitudinal MRI data across groups-healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients, including subjects that converted from MCI to AD. We started from a big database of 1250 subjects from the Alzheimer's disease neuroimaging initiative (ADNI), and we created different reduced datasets simulating real-life situations using a random-removal permutation-based approach. The number of subjects needed to differentiate groups and to detect conversion to AD was 147 and 115 respectively. The Bayesian approach allowed estimating the LME model even with very sparse databases, with high number of missing points, which was not possible with the frequentist approach. Our results indicate that the frequentist approach is computationally simpler, but it fails in modelling data with high number of missing values.

Long-Term Responders After Autologous Stem Cell Transplantation in Multiple Myeloma.

Introduction: Multiple myeloma (MM) is considered an incurable hematological neoplasm. For transplant-eligible patients, initial treatment includes an induction phase followed by an autologous stem cell transplantation (ASCT). Despite the introduction of several drugs in the past years, relapses still occur. Nevertheless, some patients achieve sustained responses after successful induction treatment and ASCT. Methods: We retrospectively evaluated all patients diagnosed with MM in our institution who underwent induction treatment and ASCT between 1990 and 2015. The subset of patients who achieved a sustained response (any degree) for 5 or more years after ASCT without further treatment or signs of progression were distinguished as "long-term responders" (LTRs). In the non-LTR group, a cohort referred to as "prolonged responders" (PLRs) showed sustained response of at least 5 years after ASCT but eventually relapsed. We collected and analyzed clinical and laboratory data. Results: Two hundred and fifty patients were diagnosed with MM and received induction treatment and ASCT at our institution in the study period. Among them, 54 (21.6%) patients met the criteria for LTR. Some diagnostic features such as a younger age, female gender, ECOG performance status of 0, lower International Staging System (ISS) stage, lower bone marrow plasma cell infiltration, and lower serum levels of calcium, C-reactive protein, and lactate dehydrogenase (LDH) were found to be more prevalent in LTR. Female gender, an ECOG performance status of 0, a localized Durie-Salmon stage, an ISS of I-II, the absence of bone disease, and an LDH within normal range were also predictive of longer progression-free survival (PFS) and overall survival (OS) in the whole cohort. The depth of the response achieved after induction and ASCT as well as the administration of an IMID-based maintenance regimen may play a role in the differences observed on PFS between cohorts. A detectable M-protein with a monoclonal gammopathy of undetermined significance (MGUS)-like behavior was detected in one-third of LTR after ASCT. Although relapses continue to occur in patients who achieve a 5-year treatment-free period after ASCT, a plateau is observed in the survival curves at approximately 21 years of follow-up.