Spinocerebellar ataxia 27B (SCA27B), a frequent late-onset cerebellar ataxia.

Genetic cerebellar ataxias are still a diagnostic challenge, and yet not all of them have been identified. Very recently, in early 2023, a new cause of late-onset cerebellar ataxia (LOCA) was identified, spinocerebellar ataxia 27B (SCA27B). This is an autosomal dominant ataxia due to a GAA expansion in intron 1 of the FGF14 gene. Thanks to the many studies carried out since its discovery, it is now possible to define the clinical phenotype, its particularities, and the progression of SCA27B. It has also been established that it is one of the most frequent causes of LOCA. The core phenotype of the disease consists of slowly progressive late-onset ataxia with cerebellar syndrome, oculomotor disorders including downbeat nystagmus, and episodic symptoms such as diplopia. Therapeutic approaches have been proposed, including acetazolamide, and 4-aminopyridine, the latter with a better benefit/tolerance profile.

[Association between students' clinical performance and their success in the computerized national ranking tests: A single-center retrospective cohort study]. / Association entre les performances cliniques des étudiants et leur réussite aux Épreuves classantes nationales informatisées : une étude de cohorte rétrospective monocentrique.

INTRODUCTION: Before attending residency, 6th-year French medical students must validate a final examination including a practical clinical test in their faculty. However, the national ranking that determines their future specialty and region solely relies on a computerized knowledge test. Our goal was to investigate the association between the final faculty test and the national ranking test. METHODS: In our faculty, the final examination includes a computerized theoretical test (similar to the national one) and a practical test: a standardized evaluation of semiology skills at the bedside and a standardized assessment of relational skills with role plays. The agreements between the national test and faculty computerized and practical tests were analyzed by intraclass correlation coefficients (ICC). RESULTS: Data from 1806 students who underwent the three examinations from 2017 to 2021 were analyzed. There was a good agreement between the ranks in the faculty and national computerized tests: ICC 0.83 (95% CI 0.81-0.85). By contrast, the agreement between the ranks in the faculty practical test and the national computerized test was poor: ICC 0.13 (95% CI 0.08-0.17). Results were stable over the years. CONCLUSION: The agreement between the ranking of the current national test and the clinical skills assessed by a specific faculty test is poor. This could relate to a true independence or to different levels of motivation to perform well. Indeed, the result of the national test is the most important one as it determines their career. Incorporating a clinical assessment into the national ranking test will motivate students to acquire clinical skills and value those who perform well this practical dimension.

Progressive clinical case-based multiple-choice questions: An innovative way to evaluate and rank undergraduate medical students.

INTRODUCTION: In France, at the end of the sixth year of medical studies, students take a national ranking examination including progressive clinical case-based multiple-choice questions (MCQs). We aimed to evaluate the ability of these MCQs for testing higher-order thinking more than knowledge recall, and to identify their characteristics associated with success and discrimination. METHODS: We analysed the 72 progressive clinical cases taken by the students in the years 2016-2019, through an online platform. RESULTS: A total of 72 progressive clinical cases (18 for each of the 4 studied years), corresponding to 1059 questions, were analysed. Most of the clinical cases (n=43, 60%) had 15 questions. Clinical questions represented 89% of all questions, whereas basic sciences questions accounted for 9%. The most frequent medical subspecialties were internal medicine (n=90, 8%) and infectious diseases (n=88, 8%). The most frequent question types concerned therapeutics (26%), exams (19%), diagnosis (14%), and semiology (13%). Level 2 questions ("understand and apply") accounted for 59% of all questions according to the Bloom's taxonomy. The level of Bloom's taxonomy significantly changed over time with a decreasing number of level 1 questions ("remember") (P=0.04). We also analysed the results of the students among 853 questions of training ECNi. Success and discrimination significantly decreased when the number of correct answers increased (P<0.0001 both). The success, discrimination, mean score, and mean number of discrepancies did not differ according to the diagnosis, exam, imaging, semiology, or therapeutic type of questions. CONCLUSION: Progressive clinical case-based MCQs represent an innovative way to evaluate undergraduate students.

Are script concordance tests suitable for the assessment of undergraduate students? A multicenter comparative study.

INTRODUCTION: Script concordance tests (SCTs) have been developed to assess clinical reasoning in uncertain situations. Their reliability for the evaluation of undergraduate medical students has not been evaluated. METHODS: Twenty internal medicine SCT cases were implemented in undergraduate students of two programs. The results obtained on the SCTs were compared to those obtained by the same students on clinical-based classical multiple-choice questions (MCQs). RESULTS: A total of 551/883 students (62%) answered the SCTs. The mean aggregate score (based on a total 20 points) was 11.54 (3.29). The success rate and mean score for each question did not differ depending on the modal response but the discrimination rate did. The results obtained by the students on the SCT test correlated with their scores on the MCQ tests. Among students, 446/517 (86%) considered the SCTs to be more difficult than classical MCQs, although the mean score did not differ between the SCT and MCQ tests. CONCLUSION: The use of SCTs is a feasible option for the evaluation of undergraduate students. The SCT scores correlated with those obtained on classical MCQ tests.

Pseudoxanthoma elasticum overlaps hereditary spastic paraplegia type 56.

PURPOSE: Pseudoxanthoma elasticum (PXE) is a recessive disorder involving skin, eyes and arteries, mainly caused by ABCC6 pathogenic variants. However, almost one fifth of patients remain genetically unsolved despite extensive genetic screening of ABCC6, as illustrated in a large French PXE series of 220 cases. We searched for new PXE gene(s) to solve the ABCC6-negative patients. METHODS: First, family-based exome sequencing was performed, in one ABCC6-negative PXE patient with additional neurological features, and her relatives. CYP2U1, involved in hereditary spastic paraplegia type 56 (SPG56), was selected based on this complex phenotype, and the presence of two candidate variants. Second, CYP2U1 sequencing was performed in a retrospective series of 46 additional ABCC6-negative PXE probands. Third, six additional SPG56 patients were evaluated for PXE skin and eye phenotype. Additionally, plasma pyrophosphate dosage and functional analyses were performed in some of these patients. RESULTS: 6.4% of ABCC6-negative PXE patients (n = 3) harboured biallelic pathogenic variants in CYP2U1. PXE skin lesions with histological confirmation, eye lesions including maculopathy or angioid streaks, and various neurological symptoms were present. CYP2U1 missense variants were confirmed to impair protein function. Plasma pyrophosphate levels were normal. Two SPG56 patients (33%) presented some phenotypic overlap with PXE. CONCLUSION: CYP2U1 pathogenic variants are found in unsolved PXE patients with neurological findings, including spastic paraplegia, expanding the SPG56 phenotype and highlighting its overlap with PXE. The pathophysiology of ABCC6 and CYP2U1 should be explored to explain their respective role and potential interaction in ectopic mineralization.

El futuro: ¿Hygeia versus Panakeia? / The future: Hygeia versus Panakeia?

En la antigüedad, Asklepios era el dios de la salud. Aunque según la mitología fue sacudido por un trueno en el culmen de su gloria por intentar resucitar a un muerto a cambio de una gran cantidad de dinero, su culto es el que más ha persistido de entre los dioses griegos. Asklepios tenía dos hijas, Hygeia y Panakeia. Esta última era una auténtica diosa de la curación, versada en el uso de las drogas derivadas de las plantas, o de la tierra; en la actualidad, su culto se halla en buen estado, visible en la búsqueda universal de la panacea. Su hermana Hygeia, en cambio, era la diosa para la cual la salud constituía el orden natural de las cosas. Enseñó a los griegos que, viviendo de acuerdo con la razón, con moderación en todos los ámbitos, podían permanecer sanos. Todavía honramos su memoria usando la palabra higiene. Hoy día, en este mundo dominado por lo tecnológico en que vivimos, ambos puntos de vista se hallan más enfrentados que...(AU)

Acute smell and taste loss in outpatients: all infected with SARS-CoV-2?

During SARS-CoV-2 pandemic, our region (Alsace, East of France) became a Covid-19 cluster quite early in Europe. Loss of smell and taste was quickly flagged by the Ears-Nose and Throat scientific community as a potential warning signs of SARS-CoV-2 infection (1). Many patients and medical/paramedical workers with mild to moderate form of SARS-CoV-2 infection complained about their loss of sense of smell and taste to our ENT department. The aim of our study was to compare the characteristics of loss of smell and taste between patients with a clinical diagnosis of SARS-CoV-2 infection to patients with a RT-PCR diagnosis.

Process evaluation of 'Brains Ahead!': an intervention for children and adolescents with mild traumatic brain injury within a randomized controlled trial.

OBJECTIVE: To investigate whether the 'Brains Ahead! Intervention for children and adolescents with mild traumatic brain injury' was implemented as intended. In addition, involvement in and satisfaction with the intervention among patients, caregivers and professionals delivering the intervention were studied. DESIGN: Mixed methods, prospective study. PARTICIPANTS: Children with mild traumatic brain injury and their caregivers, allocated to the intervention group of the randomized controlled trial in the 'Brains Ahead!' study, and the two professionals providing the intervention. INTERVENTION: The intervention consists of a standardized and individualized psychoeducational session with written take-home information, and follow-up telephone call(s). MAIN MEASURES: Registration forms, evaluation questionnaires for patients and caregivers and semi-structured interviews for professionals. DATA ANALYSIS: Qualitative data were categorized based on content. Quantitative data were reported as descriptive statistics. RESULTS: Fifty-five patients and caregivers out of 60 study-participants attended both sessions. All elements of the intervention were delivered to 53 study-participants. Evaluation questionnaires were completed by 21 of the 31 patients aged 12 years and older, and by 41 caregivers. Overall, the sessions were considered useful by 19 patients, 40 caregivers and both professionals. Reassurance, creating a better understanding and recognition of symptoms were rated as important aspects. On a scale from 1 to 10, the intervention was rated by children, caregivers and professionals with 7.6 (SD 1.2), 8.1 (SD .9) and 8.0 (SD .0), respectively. CONCLUSION: The 'Brains Ahead!' intervention was largely implemented as intended and the process evaluation revealed that it is considered feasible according to patients, caregivers and professionals.

New Measurement of

Carbon and oxygen burning reactions, in particular, ^{12}C+^{12}C fusion, are important for the understanding and interpretation of the late phases of stellar evolution as well as the ignition and nucleosynthesis in cataclysmic binary systems such as type Ia supernovae and x-ray superbursts. A new measurement of this reaction has been performed at the University of Notre Dame using particle-γ coincidence techniques with SAND (a silicon detector array) at the high-intensity 5U Pelletron accelerator. New results for ^{12}C+^{12}C fusion at low energies relevant to nuclear astrophysics are reported. They show strong disagreement with a recent measurement using the indirect Trojan Horse method. The impact on the carbon burning process under astrophysical scenarios will be discussed.

Effectiveness of the Brains Ahead! Intervention: 6 Months Results of a Randomized Controlled Trial in School-Aged Children With Mild Traumatic Brain Injury.

OBJECTIVE: To examine the effectiveness of Brains Ahead!, a psychoeducational intervention aimed to prevent long-term problems with activities and participation in children after mild traumatic brain injury (mTBI). PARTICIPANTS: In total, 124 children, aged 6 to 18 years, diagnosed with mTBI and their caregivers. METHOD: After randomization, participants in the intervention group received a face-to-face psychoeducational session with written take-home information and follow-up telephone call(s). Participants in the control group received usual care, consisting of a concise information brochure. PRIMARY OUTCOME MEASURES: Activities and participation (Child and Adolescent Scale of Participation [CASP]). SECONDARY OUTCOMES: fatigue, postconcussive symptoms (PCSs), posttraumatic stress symptoms (PTSSs), and quality of life (QOL). RESULTS: Generalized Estimated Equation analyses showed that both groups improved over the first 6 months post-mTBI, but the intervention group did not differ significantly on the CASP. Mann-Whitney U tests showed that the intervention group reported significantly less fatigue, PCSs, and PTSSs and better QOL compared with the control group at 6 months post-MTBI. CONCLUSIONS: The Brains Ahead! intervention resulted in significant improvements compared with usual care in reducing fatigue, PCSs, and PTSSs and improving QOL. Lack of an effect on activities and participation may be due to the ceiling effect of the CASP.

Activities and Participation in the First 6 Months After Mild Traumatic Brain Injury in Children and Adolescents.

OBJECTIVE: To investigate the natural course of activities and participation of children up to 6 months after a mild traumatic brain injury (mTBI). METHODS: A prospective longitudinal cohort study with complete data sets of 231 children diagnosed with mTBI and their caregivers. MAIN MEASURES: Activities and participation assessed with the Child and Adolescent Scale of Participation (CASP) and the Children's Assessment of Participation and Enjoyment (CAPE) measured at 2 weeks, 3 months, and 6 months post-mTBI. Because of a ceiling effect, the primary outcome measure (CASP) was divided into deviant (not maximum score) or full functioning. RESULTS: Friedman's, Cochran's Q, and McNemar's tests (CASP) and repeated-measures analyses of variance (CAPE) showed significant increases in activities and participation between 2 weeks and 3 and 6 months after mTBI. Based on the parents' perspective, 67% of the children returned to full functioning at 6 months postinjury, with only 38% of the children describing themselves as functioning at their premorbid level. DISCUSSION: Findings indicate that most children return to maximum level of activities and participation over time after mTBI. In a substantial number of children, however, the level of activities and participation at 6 months postinjury is evaluated as lower than that of peers. The importance of investigating predictors for child and caregiver perspectives is emphasized.

Self-Extubation Revisited: A Case-Control Study.

BACKGROUND: To increase the understanding of the self-extubation phenomena, we assessed its rate in our medical ICU and aimed to identify the risk factors of self-extubation and the risk factors for re-intubation. METHODS: We prospectively identified subjects who self-extubated. Their baseline characteristics, including the Richmond Agitation Severity Scale score, reason for intubation, shift, distance of the endotracheal tube tip to the carina, and outcomes were collected retrospectively. For every subject who self-extubated, a control subject was selected from the mechanical ventilation database. RESULTS: During the study period, there were 2,578 admissions with 4,072 mechanical ventilation days. Fifty-three cases of self-extubation were recorded, which resulted in a self-extubation event rate of 1.3 per 100 days of mechanical ventilation. Forty-five controls were identified. The most common reason for intubation was hypoxic respiratory failure, followed by the need for airway protection and hypercapnic respiratory failure. Sedation was administered continuously in 34% of the subjects. Thirty-seven percent received no sedation. At the time of the event, the subjects who self-extubated had a higher Richmond Agitation Severity Scale score, a longer distance from the endotracheal tip to carina on the chest radiograph preceding the event, and a shorter duration of mechanical ventilation, and were more likely to be on volume-controlled mechanical ventilation. ICU mortality was lower in the self-extubation group, despite having a trend toward a higher Simplified Acute Physiology Score II. Sixteen subjects required re-intubation. Independent predictors of re-intubation were hypoxic respiratory failure as the reason for the initial intubation and self-extubation that occurred at night. The need for re-intubation was not associated with higher mortality. CONCLUSIONS: Results of our study showed that, in the era of reduced use of sedatives in the ICU, clinicians must be vigilant of the risk of self-extubation in the first 2 d of mechanical ventilation in patients who are agitated and with a longer endotracheal tube to carina distance on chest radiograph.

Prevalence and characterisation of vocal fold motion impairment (VFMI) in patients with Multiple system atrophy compared with Parkinson's disease.

INTRODUCTION: Multiple system atrophy (MSA) is a neurodegenerative disorder in which vocal fold mobility can be affected, sometimes leading to life-threatening situations. Our aim was to know if laryngeal examination could help differentiate MSA from Parkinson's disease (PD). MATERIALS AND METHODS: Between 2004 to 2014, all consecutive patients diagnosed with probable MSA were included in this retrospective, monocentric study. Flexible laryngoscopy was obtained in 51 MSA patients and compared with 27 patients with Parkinson's disease (PD). Laryngeal muscles EMG was available in 6 MSA patients. RESULTS: Vocal fold motion impairments (VFMI) was found in 35 (68.6%) MSA patients: 15 (29.4%) had uni- or bilateral vocal fold abnormal movement (VFAM), 13 (25.5%) had uni- or bilateral vocal fold abductor paresis (VFABP), 4 (7.8%) had uni- or bilateral vocal fold adductor paresis (VFADP), 10 (19.6%) had bilateral vocal fold paralysis (BVFP). VFMI was found in 13 PD patients (48.1%) all of whom had VFADP. Presence of BVFP was found associated with stridor (P<0.001) and dysphagia (P=0.002). In all muscles examined in 6 MSA patients, the EMG showed neuropathic patterns. CONCLUSIONS: Our data support that VFMI may be encountered in two-thirds of MSA with a variable degree of gravity. Laryngological examination should be considered as a supplementary tool for the diagnosis and prognosis of MSA. VFMI in particular VFAM, VFABD and BVFP should be discussed as an additional possible red flag even at an early stage of MSA and could help discriminate MSA from PD.

Predictors of activities and participation six months after mild traumatic brain injury in children and adolescents.

OBJECTIVE: This study aimed to identify predictors of long-term consequences for activities and participation in children and adolescents with mild traumatic brain injury (mTBI). METHODS: A multicentre prospective longitudinal cohort study was conducted. The primary outcome measure was activities and participation measured with the Child and Adolescent Scale of Participation - CASP and completed by children (N = 156) and caregivers (N = 231) six months post-mTBI. The CASP items were categorized into home, community, school, and environment. Predictors were categorized according to the International Classification of Functioning, Disability and Health for Children and Youth. Predictors included pre-injury personal- and environmental factors, injury-related factors, symptoms, and resumption of activities in the first two weeks after mTBI. Univariate and multivariate logistic regression analyses were used to determine the predictive value of these factors. RESULTS: Results show that predictors differ across settings and perspectives (child or caregiver). Decreased activities and participation in children with mTBI can be predicted by adverse pre-injury behavioral functioning of the child (p < .000 - p = .038), adverse pre-injury family functioning (p = .001), lower parental SES (p = .038), more stress symptoms post-injury (p = .017 - p = .032), more post-concussive symptoms (p = .016 - p = .028) and less resumption of activities (p = .006 - p = .045). DISCUSSION: Pre-injury factors, more symptoms post-injury and less resumption of activities should be considered when children are screened for unfavorable outcomes. Additional factors may add to the prediction, but injury-related factors do not. It is recommended that future research explores psychosocial factors, such as coping styles, emotion-regulation, personality traits, social support, and other comorbid problems of both children and caregivers.

The "Neurological Hat Game": A fun way to learn the neurological semiology.

INTRODUCTION: In-class courses are deserted by medical students who tend to find it more beneficial to study in books and through online material. New interactive teaching methods, such as serious games increase both performance and motivation. We developed and assessed a new teaching method for neurological semiology using the "Hat Game" as a basis. METHODS: In this game, two teams of second-year medical students are playing against one another. The game is played with a deck of cards. A neurological symptom or sign is written on each card. Each team gets a predefined period of time to guess as many words as possible. One member is the clue-giver and the others are the guessers. There are three rounds: during the first round, the clue-giver uses any descriptive term he wants and as many as he wants to make his team guess the maximum number of words within the allocated time. During the second round, the clue-giver can only choose one clue-word and, during the third round, he mimes the symptom or sign. The team that has guessed the most cards wins the game. To assess the efficacy of this learning procedure, multiple choices questions (MCQs) were asked before and after the game. Exam results of second-year students on their final university Neurology exam were analyzed. A satisfaction survey was proposed to all participating students. RESULTS: Among 373 students, 121 volunteers (32.4%) were enrolled in the "Neurology Hat Game" and 112 attended the game. One hundred and seven of the 112 students completed the MCQs with a significant improvement in their responses after the game (P<0.001). The 112 students who completed the satisfaction self-administered questionnaire were very satisfied with this funny new teaching method. CONCLUSIONS: Teaching neurological semiology via the "Hat Game" is an interesting method because it is student-centered, playful and complementary to the lecturer-centered courses. A randomized controlled study would be necessary to confirm these preliminary results.

Iatrogenic meningoencephalocele after traumatic perforation of the cribriform plate during nasal intubation of a preterm infant.

Traumatic iatrogenic meningoencephaloceles infants are rare and there is no consensus on management in the literature. This article presents a case of a meningoencephalocele diagnosed 15 months after a traumatic perforation of the cribriform plate due to a difficult intubation of a preterm infant that was treated by an endoscopic endonasal surgery. A close collaboration between pediatricians and ENT surgeons appears essential for early diagnosis and management. Endoscopic endonasal approach for meningoencephalocele management has several advantages and is a safe procedure when performed by an experienced surgeon.

The Brains Ahead! intervention for children and adolescents with mild traumatic brain injury and their caregivers: rationale and description of the treatment protocol.

PURPOSE:: Approximately 20% of the children and adolescents after mild traumatic brain injury will not fully recover. They suffer long-term postconcussive symptoms and may experience limitations in activities and participation. Research suggests that early psychoeducational interventions may prevent long-term postconcussive symptoms. The Brains Ahead! intervention was developed to prevent long-term symptoms and, furthermore, to establish a more successful return to activities and participation after mild traumatic brain injury in children and adolescents. The intervention is currently being evaluated in a multicenter randomized controlled trial. RATIONALE:: Providing individualized information and personal advice in addition to standardized information about the injury and possible consequences early after the injury may enable patients and caregivers to recognize and anticipate on relevant symptoms at an early stage and to prevent problems in activities and participation. THEORY INTO PRACTICE:: The Brains Ahead! intervention is a psychoeducational intervention for children and adolescents who sustained a mild traumatic brain injury and for their caregivers. The patients will receive a partially standardized and partially individualized psychoeducational session and a telephone follow-up within the first two to eight weeks after the injury.

Prospective study of relevance of 123I-MIBG myocardial scintigraphy and clonidine GH test to distinguish Parkinson's disease and multiple system atrophy.

BACKGROUND: 123I-MIBG myocardial scintigraphy and clonidine growth hormone test (CGH test) may help to distinguish multiple system atrophy (MSA) from Parkinson's disease (PD). Their relevance in the first-stage parkinsonism of uncertain etiology is unknown. METHODS: Patients experiencing parkinsonism of ambiguous etiology were clinically classified into the PD group or the MSA group as initial clinical diagnosis (ICD). Then, CGH test and myocardial scintigraphy were performed. Clinical assessment was repeated throughout the disease course until the final clinical diagnosis (FCD) could be established according to the criteria of PD and MSA, respectively. RESULTS: Twenty-five patients with uncertain diagnosis were included (15 MSA and 10 PD as ICD). At the end of a 6-year follow-up, FCD was MSA in 11/25 patients and PD in 14/25. The CGH test and the scintigraphy showed a sensitivity of 82%, and a specificity of 71 and 93%, respectively, for the diagnosis of MSA. The combination of a normal scintigraphy (i.e., with myocardial MIBG uptake) with genitourinary dysfunction was the most relevant test to diagnose MSA, whereas an abnormal scintigraphy with a levodopa response of > 30% or an abnormal scintigraphy with the absence of OH was the most relevant combinations to diagnose PD. All these combinations had an accuracy superior than 90% and a specificity of 100%. CONCLUSION: Combinations of myocardial scintigraphy with genitourinary dysfunction, levodopa response of > 30%, or orthostatic hypotension could be of interest for the distinction between PD and MSA when the clinical diagnosis remains ambiguous at the first stage of the disease.