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Aim: To develop a short version of the original Hammersmith Infant Neurological Examination (HINE) to be used as a screening tool (Brief-HINE) and to establish if the short examination maintains good accuracy and predictive power for detecting infants with cerebral palsy (CP). Method: Eleven items were selected from the original HINE (‘visual response’; ‘trunk posture’; ‘movement quantity’; ‘movement quality’; ‘scarf sign’; ‘hip adductor angles’; ‘popliteal angle’; ‘pull to sit’; ‘lateral tilting’; ‘forward parachute reaction’; ‘tendon reflexes’) identifying those items previously found to be more predictive of CP in both low- and high-risk infants. In order to establish the sensitivity of the new module, the selected items were applied to existing data, previously obtained using the full HINE at 3, 6, 9, and 12 months, in 228 infants with typical development at 2 years and in 82 infants who developed CP. Results: Brief-HINE scores showed good sensitivity and specificity, at each age of assessment, for detecting infants with CP. At 3 months, a score of less than 22 was associated with CP with a sensitivity of 0.88 and a specificity of 0.92; at 6, 9, and 12 months, the cut-off scores were less than 25 (sensitivity 0.93; specificity 0.87), less than 27 (sensitivity 0.95; specificity 0.81), and less than 27 (sensitivity 1; specificity 0.86) respectively. The presence of more than one warning sign, or items that are not optimal for the age of assessment, imply the need for a full examination reassessment. Interpretation: These findings support the validity of the Brief-HINE as a routine screening method and the possibility of its use in clinical practice.

Duchenne muscular dystrophy (DMD) is a neuromuscular condition characterized by muscle weakness. The Performance of upper limb (PUL) test is designed to evaluate upper limb function in DMD patients across three domains. The aim of this study is to identify frequently lost or gained PUL 2.0 abilities at distinct functional stages in DMD patients. This retrospective study analyzed prospectively collected data on 24-month PUL 2.0 changes related to ambulatory function. Ambulant patients were categorized based on initial 6MWT distance, non-ambulant patients by time since ambulation loss. Each PUL 2.0 item was classified as shift up, no change, or shift down. The study's cohort incuded 274 patients, with 626 paired evaluations at the 24-month mark. Among these, 55.1 % had activity loss, while 29.1 % had gains. Ambulant patients showed the lowest loss rates, mainly in the shoulder domain. The highest loss rate was in the shoulder domain in the transitioning subgroup and in elbow and distal domains in the non-ambulant patients. Younger ambulant patients demonstrated multiple gains, whereas in the other functional subgroups there were fewer gains, mostly tied to singular activities. Our findings highlight divergent upper limb domain progression, partly linked to functional status and baseline function.

Background: Scar burden with late gadolinium enhancement (LGE) cardiac MRI (CMR) predicts arrhythmic events in patients with postinfarction in single-center studies. However, LGE analysis requires experienced human observers, is time consuming, and introduces variability. Purpose: To test whether postinfarct scar with LGE CMR can be quantified fully automatically by machines and to compare the ability of LGE CMR scar analyzed by humans and machines to predict arrhythmic events. Materials and Methods: This study is a retrospective analysis of the multicenter, multivendor CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry. Patients with chronic heart failure, echocardiographic left ventricular ejection fraction (LVEF) of less than 50%, and LGE CMR were recruited (from January 2015 through December 2020). In the current study, only patients with ischemic cardiomyopathy were included. Quantification of total, dense, and nondense scars was carried out by two experienced readers or a Ternaus network, trained and tested with LGE images of 515 and 246 patients, respectively. Univariable and multivariable Cox analyses were used to assess patient and cardiac characteristics associated with a major adverse cardiac event (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare model performances. Results: In 761 patients (mean age, 65 years ± 11, 671 men), 83 MACEs occurred. With use of the testing group, univariable Cox-analysis found New York Heart Association class, left ventricle volume and/or function parameters (by echocardiography or CMR), guideline criterion (LVEF of ≤35% and New York Heart Association class II or III), and LGE scar analyzed by humans or the machine-learning algorithm as predictors of MACE. Machine-based dense or total scar conferred incremental value over the guideline criterion for the association with MACE (AUC: 0.68 vs 0.63, P = .02 and AUC: 0.67 vs 0.63

Background: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation. Objectives: The DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy; NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM. Methods: A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. Results: During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007). Conclusions: The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care.

Febrile infection-related epilepsy syndrome (FIRES) is a challenging condition with unfavorable outcome in most cases. Preliminary evidence suggests that some interleukins, in particular IL-1 Receptor Antagonist (IL-1RA), could be elevated due to a functional deficiency of anti-inflammatory pathways. Therefore, treatment strategies acting on innate immunity could represent a targeted treatment. We describe the case of an 11-year-old child with super-refractory status epilepticus (SE), lasting more than two months. After being treated aggressively with antiseizure medications, anesthetics and empiric treatment for autoimmune encephalitis without success, she responded to anakinra and ketogenic diet. Escalation of the therapy was supported by the finding of a very high serum level of IL-1RA. This immunomodulatory approach allowed to discharge the child from intensive care 48 days after the SE onset. After more than one year follow-up the patient has moderate intellectual disability but with good language skills; she is seizure free and without motor deficits. This case suggests that serum IL-1RA serum levels may help to support treatment escalation. Moreover, anakinra and ketogenic diet represent encouraging immunomodulatory strategies which deserve further studies and could potentially have a synergistic effect. Finally, structured neuropsychological testing is an important outcome measure that will help to define the effectiveness of different treatment strategies.

Background: Efficacy and safety of onasemnogene abeparvovec (OA) for Spinal Muscular Atrophy infants under 7 months and <8.5 kg has been reported in clinical trials. This study examines efficacy and safety predictors in a wide age (22 days–72 months) and weight (3.2–17 kg) range, also including patients previously treated with other drugs. Methods: 46 patients were treated for 12 months between January 2020 and March 2022. Safety profile was also available for another 21 patients with at least 6 month follow-up after OA infusion. 19/67 were treatment naïve when treated with OA. Motor function was measured with the CHOP-INTEND. Findings: CHOP-INTEND changes varied among age groups. Baseline score and age at OA treatment best predicted changes. A mixed model post-hoc analysis showed that in patients treated before the age of 24 months the CHOP-INTEND changes were already significant 3 months after OA while in those treated after the age of 24 months the difference was only significant 12 months after OA. Adverse events occurred in 51/67. The risk for elevated transaminases serum levels was higher in older patients. This was also true for weight and for pre-treatment with nusinersen when analysed individually. A binomial negative regression analysis showed that only age at OA treatment had a significant effect on the risk of elevated transaminases. Interpretation: Our paper describes OA 12-month follow-up showing efficacy across various age and weight groups not targeted by clinical trials. The study identifies prognostic factors for safety and efficacy in treatment selection. Funding: None.

The increasing pressure to include non ambulant Duchenne muscular dystrophy (DMD) boys in clinical trials has highlighted the need for outcome measures that could address the impact of upper limb function on activities of daily living. The aim of the present study was to establish the correlation between the recently developed Patient Reported Outcome Measure for the upper limb (PROM UL) and the observer rated functional scale Performance of Upper Limb (PUL 2.0) in a large cohort of DMD boys and young adults. As part of a larger natural history study, non ambulant DMD patients were assessed using PUL2.0 and PROM UL. One hundred and twenty-five concurrent PUL 2.0 and PROM UL evaluations from 60 non ambulant DMD boys were taken into consideration. The total PROM UL scores showed a strong correlation with both PUL 2.0 total scores and with PUL 2.0 entry item score. The strong correlation between the two tools confirms the clinical meaningfulness of the PUL2.0 and that the PROM UL can help to detect the gradient of progression of upper limb involvement.

Background: Type II spinal muscular atrophy (SMA) often leads to scoliosis in up to 90% of cases. While pharmacological treatments have shown improvements in motor function, their impact on scoliosis progression remains unclear. This study aims to evaluate potential differences in scoliosis progression between treated and untreated SMA II patients. Methods: Treatment effect on Cobb's angle annual changes and on reaching a 50° Cobb angle was analysed in treated and untreated type II SMA patients with a minimum 1.5-year follow-up. A sliding cut-off approach identified the optimal treatment subpopulation based on age, Cobb angle and Hammersmith Functional Motor Scale Expanded at the initial visit. Mann-Whitney U-test assessed statistical significance. Results: There were no significant differences in baseline characteristics between the untreated (n=46) and treated (n=39) populations. The mean Cobb angle variation did not significantly differ between the two groups (p=0.4). Optimal cut-off values for a better outcome were found to be having a Cobb angle <26° or an age <4.5 years. When using optimal cut-off, the treated group showed a lower mean Cobb variation compared with the untreated group (5.61 (SD 4.72) degrees/year vs 10.05 (SD 6.38) degrees/year; p=0.01). Cox-regression analysis indicated a protective treatment effect in reaching a 50° Cobb angle, significant in patients <4.5 years old (p=0.016). Conclusion: This study highlights that pharmacological treatment, if initiated early, may slow down the progression of scoliosis in type II SMA patients. Larger studies are warranted to further investigate the effectiveness of individual pharmacological treatment on scoliosis progression in this patient population.

Despite the early onset of clinical signs suggestive of Duchenne muscular dystrophy (DMD), a diagnosis is often not made until four years of age or older, with a diagnostic delay of up to two years from the appearance of the first symptoms. As disease-modifying therapies for DMD become available that are ideally started early before irreversible muscle damage occurs, the importance of avoiding diagnostic delay increases. Shortening the time to a definite diagnosis in DMD allows timely genetic counseling and assessment of carrier status, initiation of multidisciplinary standard care, timely initiation of appropriate treatments, and precise genetic mutation characterization to assess suitability for access to drugs targeted at specific mutations while reducing the emotional and psychological family burden of the disease. This comprehensive literature review describes the early signs of impairment in DMD and highlights the bottlenecks related to the different diagnostic steps. In summary, the evidence suggests that the best mitigation strategy for improving the age at diagnosis is to increase awareness of the early symptoms of DMD and encourage early clinical screening with an inexpensive and sensitive serum creatine kinase test in all boys who present signs of developmental delay and specific motor test abnormality at routine pediatrician visits.

There has recently been some concern on possible cognitive impairment in patients with Spinal Muscular Atrophy (SMA). The aim of this study was to assess cognitive profiles in type II and III SMA with a focus on individual indexes and possible correlations with motor function. 57 type II and III individuals, aged 3.5–17 years, were consecutively enrolled in a prospective, multicentric study. Cognitive function was assessed using age-appropriate Weschler Scales. Motor function was concomitantly assessed using disease-specific functional scales. Only 2 individuals (3%) had a intellectual disability of mild degree while the others were within normal range, with no significant difference in relation to SMA type, gender or functional status. While the overall quotients were mostly within normal range, some indexes showed wider variability. A significant positive medium correlation was found between Processing Speed Index and motor functional scores. Working memory had lower scores in type III patients compared to type II. Intellectual disability is uncommon in type II and III SMA. Motor functional abilities may play a role in some of the items contributing to the overall cognitive profile.

Objective: The aim of this study was to provide an overview of the clinical phenotypes associated with 4 SMN2 copies. Methods: Clinical phenotypes were analyzed in all the patients with 4 SMN2 copies as part of a nationwide effort including all the Italian pediatric and adult reference centers for spinal muscular atrophy (SMA). Results: The cohort includes 169 patients (102 men and 67 women) with confirmed 4 SMN2 copies (mean age at last follow-up = 36.9 ± 19 years). Six of the 169 patients were presymptomatic, 8 were classified as type II, 145 as type III (38 type IIIA and 107 type IIIB), and 8 as type IV. The remaining 2 patients were asymptomatic adults identified because of a familial case. The cross-sectional functional data showed a reduction of scores with increasing age. Over 35% of the type III and 25% of the type IV lost ambulation (mean age = 26.8 years ± 16.3 SD). The risk of loss of ambulation was significantly associated with SMA type (p < 0.0001), with patients with IIIB and IV less likely to lose ambulation compared to type IIIA. There was an overall gender effect with a smaller number of women and a lower risk for women to lose ambulation. This was significant in the adult (p = 0.009) but not in the pediatric cohort (p = 0.43). Interpretation: Our results expand the existing literature on natural history of 4 SMN2 copies confirming the variability of phenotypes in untreated patients, ranging from type II to type IV and an overall reduction of functional scores with increasing age. ANN NEUROL 2023;94:1126–1135.

Cardiac magnetic resonance (CMR) is the best-suited cardiac imaging modality to provide reliable and reproducible information regarding cardiac volumes, function, and tissue characterization. In clinical practice, artificial intelligence (AI) in CMR can be applied to the whole process, ranging from sequence reconstruction, image analysis, and reporting of findings. In sequence reconstruction, the application of AI is mainly focused on the speed of reconstruction, while in image analysis and reporting AI is primarily aimed at automating the process of segmentation of both ventricles as well as fibrotic tissue. Within the realm of tissue characterization, AI can also be helpful in the depiction of tissue abnormalities from noncontrast images. Finally, AI can be useful for prognostic stratification.

Aims: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients. Methods and results: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction [removed]3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort. Conclusion: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation.

Stress computed tomography perfusion (Stress-CTP) and computed tomography-derived fractional flow reserve (FFRCT) are functional techniques that can be added to coronary computed tomography angiography (cCTA) to improve the management of patients with suspected coronary artery disease (CAD). This retrospective analysis from the PERFECTION study aims to assess the impact of their availability on the management of patients with suspected CAD scheduled for invasive coronary angiography (ICA) and invasive FFR. The management plan was defined as optimal medical therapy (OMT) or revascularization and was recorded for the following strategies: cCTA alone, cCTA+FFRCT, cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP. In 291 prospectively enrolled patients, cCTA+FFRCT, cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP showed a similar rate of reclassification of cCTA findings when FFRCT and Stress-CTP were added to cCTA. cCTA, cCTA+FFRCT, cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP showed a rate of agreement versus the final therapeutic decision of 63%, 71%, 89%, 84% (cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP vs cCTA and cCTA+FFRCT: p < 0.01), respectively, and a rate of agreement in terms of the vessels to be revascularized of 57%, 64%, 74%, 71% (cCTA+Stress-CTP and cCTA+FFRCT+Stress-CTP vs cCTA and cCTA+FFRCT: p < 0.01), respectively, with an effective radiation dose (ED) of 2.9 ± 1.3 mSv, 2.9 ± 1.3 mSv, 5.9 ± 2.7 mSv, and 3.1 ± 2.1 mSv. The addition of FFRCT and Stress-CTP improved therapeutic decision-making compared to cCTA alone, and a sequential strategy with cCTA+FFRCT+Stress-CTP represents the best compromise in terms of clinical impact and radiation exposure.

Background and aims: Artificial intelligence (AI) is increasing its role in diagnosis of patients with suspicious coronary artery disease. The aim of this manuscript is to develop a deep convolutional neural network (CNN) to classify coronary computed tomography angiography (CCTA) in the correct Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Methods: Two hundred eighty eight patients who underwent clinically indicated CCTA were included in this single-center retrospective study. The CCTAs were stratified by CAD-RADS scores by expert readers and considered as reference standard. A deep CNN was designed and tested on the CCTA dataset and compared to on-site reading. The deep CNN analyzed the diagnostic accuracy of the following three Models based on CAD-RADS classification: Model A (CAD-RADS 0 vs CAD-RADS 1–2 vs CAD-RADS 3,4,5), Model 1 (CAD-RADS 0 vs CAD-RADS>0), Model 2 (CAD-RADS 0–2 vs CAD-RADS 3–5). Time of analysis for both physicians and CNN were recorded. Results: Model A showed a sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 47%, 74%, 77%, 46% and 60%, respectively. Model 1 showed a sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 66%, 91%, 92%, 63%, 86%, respectively. Conversely, Model 2 demonstrated the following sensitivity, specificity, negative predictive value, positive predictive value and accuracy: 82%, 58%, 74%, 69%, 71%, respectively. Time of analysis was significantly lower using CNN as compared to on-site reading (530.5 ± 179.1 vs 104.3 ± 1.4 sec, p=0.01) Conclusions: Deep CNN yielded accurate automated classification of patients with CAD-RADS.

This report describes the physics case, the resulting detector requirements, and the evolving detector concepts for the experimental program at the Electron-Ion Collider (EIC). The EIC will be a powerful new high-luminosity facility in the United States with the capability to collide high-energy electron beams with high-energy proton and ion beams, providing access to those regions in the nucleon and nuclei where their structure is dominated by gluons. Moreover, polarized beams in the EIC will give unprecedented access to the spatial and spin structure of the proton, neutron, and light ions. The studies leading to this document were commissioned and organized by the EIC User Group with the objective of advancing the state and detail of the physics program and developing detector concepts that meet the emerging requirements in preparation for the realization of the EIC. The effort aims to provide the basis for further development of concepts for experimental equipment best suited for the science needs, including the importance of two complementary detectors and interaction regions. This report consists of three volumes. Volume I is an executive summary of our findings and developed concepts. In Volume II we describe studies of a wide range of physics measurements and the emerging requirements on detector acceptance and performance. Volume III discusses general-purpose detector concepts and the underlying technologies to meet the physics requirements. These considerations will form the basis for a world-class experimental program that aims to increase our understanding of the fundamental structure of all visible matter.

The possibility to identify patients with spinal muscular atrophy through neonatal screenings has highlighted the need for clinical assessments that may systematically evaluate the possible presence of early neurological signs. The aim of this study was to use the Hammersmith Neonatal Neurological Examination (HNNE) and a module specifically designed for floppy infants to assess the possible variability of neurological findings in infants identified through neonatal screening. The infants included in this study were identified as part of a pilot study exploring neonatal screening in two Italian regions. A neurological examination was performed using the HNNE and an additional module developed for the assessment of floppy infants. Seventeen infants were identified through the screening. One patient had 1 SMN2 copy, 9 had 2 copies, 3 had 3, and 4 had more than 3 copies. Nine of the 17 infants (53%) had completely normal results on both scales, 3 had minimal signs, and the other 5 had more obvious clinical signs. The number of SMN2 copies was related to the presence of abnormal neurological signs (p = 0.036) but two SMN2 copies were associated with variable clinical signs as they were found in some infants with respectively normal examination or obvious severe early signs. Conclusions: Our results suggest that the combination of both scales increases the possibility to detect neonatal neurological signs and to define different early patterns of involvement also identifying paucisymptomatic patients.What is Known:• The use of new therapeutic options in presymptomatic SMA patients leads to a dramatic reduction of the onset and severity of the diesease.• The already existing tools commonly used in Type I SMA (HINE and CHOP-intend) may not be suitable to identify minor neurological signs in the neonatal period.What is New:• Combining the HNNE and the floppy infant module, we were able to identify early neurological signs in SMA infants identified through newborn screening&

The aim of this retrospective study was to review body mass index (BMI) in a large cohort of Italian pediatric type 2 spinal muscular atrophy (SMA) patients, aged between 0 and 20 years and to establish possible differences in relation to a number of variables such as ventilation, motor function, and survival motor neuron 2 gene copies. Cross-sectional data were collected from 102 patients for a total of 344 visits. Standard growth charts for height and weight were used as reference, with age adjusted BMI calculated using the Center for Disease and Prevention Children’s BMI Tool. In the 344 visits, weight ranged between 3.90 and 83 kg, and the BMI between 8.4 and 31.6 with a BMI/age z-scores < − 2SD present in 28% and BMI/age z-scores > + 2SD in 9% of the measurements. The BMI/age z-scores were relatively stable < 5 years of age with an increasing number of patients < − 2SD after the age of 5, and a wider range of BMI/age z-scores after the age of 13. A difference on the BMI/age z-scores was found among the different age subgroups (< 5, 5–12, ≥ 13 years). A multivariate analysis in 58 patients with longitudinal assessments showed that baseline BMI/age z-scores and gender were significantly contributing to the changes while other variables were not. Conclusion: Our results confirm that careful surveillance of weight and BMI/age z-scores is needed in type 2 SMA. Further studies, including assessments of chewing and swallowing and of lean/fat body mass, will help to better understand the possible mechanisms underlying weight issues.What is Known:• Feeding difficulties have been reported in a few studies and were invariably found in patients with type 1 SMA.• Type 2 SMA patients often have low BMI with a relevant number of patients requiring tube feeding.What is New:• Reduction in BMI/age z-score overtime appeared to depend on baseline BMI/age z-score and gender.• Patients with a low BMI/age z-score were at higher risk of developing fu

Febrile infection-related epilepsy syndrome (FIRES) is a challenging condition with unfavorable outcome in most cases. Preliminary evidence suggests that some interleukins, in particular IL-1 Receptor Antagonist (IL-1RA), could be elevated due to a functional deficiency of anti-inflammatory pathways. Therefore, treatment strategies acting on innate immunity could represent a targeted treatment. We describe the case of an 11-year-old child with super-refractory status epilepticus (SE), lasting more than two months. After being treated aggressively with antiseizure medications, anesthetics and empiric treatment for autoimmune encephalitis without success, she responded to anakinra and ketogenic diet. Escalation of the therapy was supported by the finding of a very high serum level of IL-1RA. This immunomodulatory approach allowed to discharge the child from intensive care 48 days after the SE onset. After more than one year follow-up the patient has moderate intellectual disability but with good language skills; she is seizure free and without motor deficits. This case suggests that serum IL-1RA serum levels may help to support treatment escalation. Moreover, anakinra and ketogenic diet represent encouraging immunomodulatory strategies which deserve further studies and could potentially have a synergistic effect. Finally, structured neuropsychological testing is an important outcome measure that will help to define the effectiveness of different treatment strategies.