Nuclear Analyses for the Assessment of the Loads on the ITER Radial Neutron Camera In-Port System and Evaluation of Its Measurement Performances

The radial neutron camera (RNC) is a key ITER diagnostic system designed to measure the uncollided 14- and 2.5-MeV neutrons from deuterium-tritium (DT) and deuterium-deuterium (DD) fusion reactions, through an array of detectors covering a full poloidal plasma section along collimated lines of sight (LoS). Its main objective is the assessment of the neutron emissivity/alpha source profile and the total neutron source strength, providing spatially resolved measurements of several parameters needed for fusion power estimation, plasma control, and plasma physics studies. The present RNC layout is composed of two fan-shaped collimating structures viewing the plasma radially through vertical slots in the diagnostic shielding module (DSM) of ITER Equatorial Port 1 (EP01): the ex-port subsystem and the in-port one. The ex-port subsystem, devoted to the plasma core coverage, extends from the Port Interspace to the Bioshield Plug: it consists of a massive shielding unit hosting two sets of collimators lying on different toroidal planes, leading to a total of 16 interleaved LoS. The in-port system consists of a cassette, integrated inside the port plug DSM, containing two detectors per each of the six LoS looking at the plasma edges. The in-port system must guarantee the required measurement performances in critical operating conditions in terms of high radiation levels, given its proximity to the plasma neutron source. This article presents an updated neutronic analysis based on the latest design of the in-port system and port plug. It has been performed by means of the Monte Carlo MCNP code and provides nuclear loads on the in-port RNC during normal operating conditions (NOC) and inputs for the measurement performance analysis

Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study

\ua9 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.Background and purpose: Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort. Methods: The study employed two distinct methods. MDC was calculated using distribution-based approaches to consider standard error of measurement and effect size change in a population of 321 patients (176 SMA II and 145 SMA III), allowing for stratification based on age and function. MCID was assessed using anchor-based methods (receiver operating characteristic [ROC] curve analysis and standard error) on 76 patients (52 SMA II and 24 SMA III) for whom the 12-month HFMSE could be anchored to a caregiver-reported clinical perception questionnaire. Results: With both approaches, SMA type II and type III patients had different profiles. The MCID, using ROC analysis, identified optimal cutoff points of −2 for type II and −4 for type III patients, whereas using the standard error we found the optimal cutoff points to be 1.5 for improvement and −3.2 for deterioration. Furthermore, distribution-based methods uncovered varying values across age and functional status subgroups within each SMA type. Conclusions: These results emphasize that the interpretation of a single MCID or MDC value obtained in large cohorts with different functional status needs to be made with caution, especially when these may be used to assess possible responses to new therapies

Non-interventional, retrospective data of long-term home parenteral nutrition in patients with benign diseases: Analysis of a nurse register (SERECARE)

Objectives: The aim of this study was to evaluate the safety and efficacy of home parenteral nutrition (HPN) service in patients with benign chronic intestinal failure (CIF). Methods: This was a 10-y retrospective, non-interventional, multicenter study conducted with adult and pediatric patients with CIF who received HPN service. We analyzed data prospectively collected from a dedicated register by HPN nurses. Results: From January 2002 to December 2011 a total of 794 patients (49.7% male, median age 1 y for children and 57 y for adults) were included in the analysis. Over the 10-y period, 723 central venous catheter (CVC) complications occurred, of which 394 were infectious (54.5%), 297 were mechanical (41.1%), and 32 (3.3%) were defined as CVC-related thrombosis. The complication rate was higher in children (1.11 per patient) than in adults (0.70 per patient). During the observation period, the rates of both infectious and mechanical complications showed a global declining trend and 3c75% of patients had neither infectious nor mechanical CVC complications. HPN efficacy was evaluated in 301 patients with a minimum follow-up of 36 mo. Body mass index and Karnofsky score showed that the median growth significantly increased (P < 0.001) over baseline for adults and pediatric patients in the 0 to 2 age range. Conclusions: The use of a structured register has proved to be a key strategy for monitoring the outcomes of long-term treatment, improving time efficiency, and preventing potential malpractice. To our knowledge, this is largest survey ever documented; the results were consistent despite the heterogeneity of the centers because of duly applied standard rules and protocols

Pediatric SARS-CoV-2-Related Diplopia and Mesencephalic Abnormalities

ObjectiveThis case report describes a patient with mesencephalic MRI signal abnormality and diplopia, possibly associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsWe describe a boy with binocular diplopia and nystagmus. The pattern of serology positivity and negative direct research of SARS-CoV-2 RNA in our patient allowed us to consider novel coronavirus as the trigger of possible immune-mediated phenomena against the central nervous system.ResultsDuring hospitalization, blood tests revealed a recent SARS-CoV-2 infection. MRI revealed hyperintensity of the mesencephalic tegmentum and periaqueductal region, consistent with an inflammatory lesion of the midbrain tegmentum. Viral and bacterial molecular screening on cerebrospinal fluid and isoelectrofocusing analysis, anti-myelin oligodendrocyte glycoprotein, anti-Aquaporine-4, and anti-N-methyl-d-Aspartate antibodies were negative. The patient was treated with steroids and immunoglobulin therapy with complete remission of neurologic symptoms.DiscussionThis report expands the spectrum of pediatric COVID-19-Associated neurologic symptoms and highlights a possible isolated neurologic COVID-19-related symptom

Musculoskeletal features without ataxia associated with a novel de novo mutation in KCNA1 impairing the voltage sensitivity of Kv1.1 channel

The KCNA1 gene encodes the \u3b1 subunit of the voltage-gated Kv1.1 potassium channel that critically regulates neuronal excitability in the central and peripheral nervous systems. Mutations in KCNA1 have been classically associated with episodic ataxia type 1 (EA1), a movement disorder triggered by physical and emotional stress. Additional features variably reported in recent years include epilepsy, myokymia, migraine, paroxysmal dyskinesia, hyperthermia, hypomagnesemia, and cataplexy. Interestingly, a few individuals with neuromyotonia, either isolated or associated with skeletal deformities, have been reported carrying variants in the S2\u2013S3 transmembrane segments of Kv1.1 channels in the absence of any other symptoms. Here, we have identified by whole-exome sequencing a novel de novo variant, T268K, in KCNA1 in a boy displaying recurrent episodes of neuromyotonia, muscle hypertrophy, and skeletal deformities. Through functional analysis in heterologous cells and structural modeling, we show that the mutation, located at the extracellular end of the S3 helix, causes deleterious effects, disrupting Kv1.1 function by altering the voltage dependence of activation and kinetics of deactivation, likely due to abnormal interactions with the voltage sensor in the S4 segment. Our study supports previous evidence suggesting that specific residues within the S2 and S3 segments of Kv1.1 result in a distinctive phenotype with predominant musculoskeletal presentation

Body mass indePEx in type 2 spinal muscular atrophy: a longitudinal study

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 further reduction

Sometimes they come back: New and old spinal muscular atrophy adults in the era of nusinersen

Background and purpose: Following the commercial availability of nusinersen, there have been a number of new referrals of adults with spinal muscular atrophy (SMA) not regularly followed in tertiary-care centers or enrolled in any disease registry. Methods: We compared demographics and disease characteristics, including assessment of motor and respiratory function, in regularly followed patients and newcomers subdivided according to the SMA type. Results: The cohort included 166 adult patients (mean age: 37.09 years): one type I, 65 type II, 99 type III, and one type IV. Of these 166, there were 67 newcomers. There was no significant difference between newcomers and regularly followed patients in relation to age and disease duration. The Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module scores were higher in the regularly followed patients compared to newcomers in the whole cohort and in both SMA II and II. A difference was also found on ventilatory status (p = 0.013) and Cobb’s angle >50° (p = 0.039) between the two subgroups. No difference was found in scoliosis surgery prevalence (p > 0.05). Conclusions: Our results showed differences between the two subgroups, even if less marked in the type III patients. In the type II patients, there was a higher proportion of newcomers who were in the severe end of the spectrum. Of the newcomers, only approximately a third initiated treatment, as opposed to the 51% in the regularly followed patients. The identification of patients who were not part of the registries will help to redefine the overall prevalence of SMA and the occurrence of different phenotypes