Neurofibromatosis type 1 mosaicism in patients with constitutional mismatch repair deficiency.

Differential diagnosis between constitutional mismatch repair deficiency (CMMRD) and neurofibromatosis type 1 (NF1) is crucial as treatment and surveillance differ. We report the case of a girl with a clinical diagnosis of sporadic NF1 who developed a glioblastoma. Immunohistochemistry for MMR proteins identified PMS2 loss in tumour and normal cells and WES showed the tumour had an ultra-hypermutated phenotype, supporting the diagnosis of CMMRD. Germline analyses identified two variants (one pathogenic variant and one classified as variant(s) of unknown significance) in the PMS2 gene and subsequent functional assays on blood lymphocytes confirmed the diagnosis of CMMRD. The large plexiform neurofibroma of the thigh and the freckling were however more compatible with NF1. Indeed, a NF1 PV (variant allele frequencies of 20%, 3% and 9% and in blood, skin and saliva samples, respectively) was identified confirming a mosaicism for NF1. Retrospective analysis of a French cohort identified NF1 mosaicism in blood DNA in 2 out of 22 patients with CMMRD, underlining the existence of early postzygotic PV of NF1 gene in patients with CMMRD whose tumours have been frequently reported to exhibit somatic NF1 mutations. It highlights the potential role of this pathway in the pathogenesis of CMMRD-associated gliomas and argues in favour of testing MEK inhibitors in this context.

Co-existence of depression and post-concussion syndrome one month after mild traumatic brain injury.

BACKGROUND: Previous studies suggest an association between Post-concussion syndrome (PCS) and depression, both highly prevalent after mTBI. OBJECTIVE: To assess the prevalence and risk-factors of depression among patients with PCS 1 month after mTBI. METHODS: We prospectively screened 372 mTBI patients admitted in two academic Emergency Departments between 2017 and 2019. One month after mTBI, we administered the Rivermead Post-concussion symptoms Questionnaire (RPQ) and the Patient Health Questionnaire (PHQ-9) questionnaires over the telephone. PCS and depression were defined by RPQ ≥ 12 and PHQ-9 ≥ 10. Multivariate multinomial regression identified baseline factors associated with PCS and depression. RESULTS: Two hundred and eight completed RPQ and PHQ-9. Forty-seven patients (22.5%) met criteria for PCS, among which 22 (46.8%) met criteria for depression (PCS+D+). Patients with PCS but without depression were less likely to present with an associated injury (Coefficient = -1.6, p = 0.047) and to report initial sadness (Coefficient = -2.5, p = 0.03). Initial sadness (Coefficient = -1.3, p = 0.047), associated injury (Coefficient = -1.9, p = 0.008), as well as initial nausea (Coefficient = -1.8, p = 0.002), and male sex (Coefficient = 1.8, p = 0.002), were associated with the absence of depression and PCS in comparison with PCS+D+ patients. CONCLUSION: Among patients with PCS 1 month after mTBI, those with depression are more likely to present with initial sadness and with an associated injury.

A Minimal PBPK Model for Plasma and Cerebrospinal Fluid Pharmacokinetics of Trastuzumab after Intracerebroventricular Administration in Patients with HER2-Positive Brain Metastatic Localizations.

BACKGROUND: Dosing regimens of trastuzumab administered by intracerebroventricular (icv) route to patients with HER2-positive brain localizations remain empirical. The objectives of this study were to describe pharmacokinetics (PK) of trastuzumab in human plasma and cerebrospinal fluid (CSF) after simultaneous icv and intravenous (iv) administration using a minimal physiologically-based pharmacokinetic model (mPBPK) and to perform simulations of alternative dosing regimens to achieve therapeutic concentrations in CSF. METHODS: Plasma and CSF PK data were collected in two patients with HER2-positive brain localizations. A mPBPK model for mAbs consisting of four compartments (tight and leaky tissues, plasma and lymph) was enriched by an additional compartment for ventricular CSF. The comparison between observed and model-predicted concentrations was evaluated using prediction error (PE). RESULTS: The developed mPBPK model described plasma and CSF trastuzumab concentrations reasonably well with mean PE for plasma and CSF data of 41.8% [interquartile range, IQR = -9.48; 40.6] and 18.3% [-36.7; 60.6], respectively, for patient 1 and 11.4% [-10.8; 28.7] and 22.5% [-27.7; 77.9], respectively, for patient 2. Trastuzumab showed fast clearance from CSF to plasma with Cmin,ss of 0.56 and 0.85 mg/L for 100 and 150 mg q1wk, respectively. Repeated dosing of 100 and 150 mg q3day resulted in Cmin,ss of 10.3 and 15.4 mg/L, respectively. Trastuzumab CSF target concentrations are achieved rapidly and maintained above 60 mg/L from 7 days after a continuous perfusion at 1.0 mg/h. CONCLUSION: Continuous icv infusion of trastuzumab at 1.0 mg/h could be an alternative dosing regimen to rapidly achieve intraventricular CSF therapeutic concentrations.

How is Video Efficient to Diagnose Sport-Related Concussion? A Cross-Sectional Study in the French TOP14 Rugby Championship.

OBJECTIVE: To describe the frequency of clinical signs and the accuracy of video diagnosis of sport-related concussion. DESIGN: An observational cross-sectional study. SETTING AND PARTICIPANTS: Videos from a database of all suspected sport-related concussion in TOP14 matches (French professional male rugby Championship) were used, from 2012 to 2015 seasons. The videos were analyzed by 4 observers, blinded to the concussion diagnosis, after a training phase, and an inter-rater reliability analysis. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Video analysis for clinical signs and presumed diagnosis of sport-related concussion. The observer's diagnosis was compared with the team physicians' diagnosis. RESULTS: Four hundred seventeen videos were analyzed with 142 concussed players. Sport-related concussions happened mostly from an impact to the head (seen by the observers in 98.4%), against an opponent (73.2%), and during a tackle (74.6%). Video signs were observable in 98.6% for suspected loss of consciousness, tonic posturing (95%), ataxia (77.2%), dazed look (35.7%), abnormal behavior (18.2%), and seizures (96.2%). Ataxia was seen in 77.7% of concussed players, suspected loss of consciousness in 61.4%, dazed look in 63.2%, abnormal behavior in 55%, and tonic posturing in 7.1%. The observers diagnosed 79.8% of concussions. CONCLUSIONS: We described the frequency of video clinical signs of sport-related concussion, with a good accuracy of the blinded observers for the diagnosis. This emphasizes the importance of pitch-side video analysis as an extra tool for sport-related concussion diagnosis.

Surface reconstruction from routine CT-scan shows large anatomical variations of falx cerebri and tentorium cerebelli.

BACKGROUND: Finite element modeling of the human head offers an alternative to experimental methods in understanding the biomechanical response of the head in trauma brain injuries. Falx, tentorium, and their notches are important structures surrounding the brain, and data about their anatomical variations are sparse. OBJECTIVE: To describe and quantify anatomical variations of falx cerebri, tentorium cerebelli, and their notches. METHODS: 3D reconstruction of falx and tentorium was performed by points identification on 40 brain CT-scans in a tailored Matlab program. A scatter plot was obtained for each subject, and 8 anatomical landmarks were selected. A reference frame was defined to determine the coordinates of landmarks. Segments and areas were computed. A reproducibility study was done. RESULTS: The height of falx was 34.9 ± 3.9 mm and its surface area 56.5 ± 7.7 cm2. The width of tentorium was 99.64 ± 4.79 mm and its surface area 57.6 ± 5.8 cm2. The mean length, height, and surface area of falx notch were respectively 96.9 ± 8 mm, 41.8 ± 5.9 mm, and 28.8 ± 5.8 cm2 (range 15.8-40.5 cm2). The anterior and maximal widths of tentorial notch were 25.5 ± 3.5 mm and 30.9 ± 2.5 mm; its length 54.9 ± 5.2 mm and its surface area 13.26 ± 1.6 cm2. The length of falx notch correlated with the length of tentorial notch (r = 0.62, P < 0.05). CONCLUSION: We observe large anatomical variations of falx, tentorium, and notches, crucial to better understand the biomechanics of brain injury, in personalized finite element models.

What Is the Impact of Physical Effort on the Diagnosis of Concussion?

OBJECTIVE: Sport-related concussion commonly occurs in contact sports such as rugby. To date, diagnosis is based on the realization of clinical tests conducted pitch-side. Yet, the potential effect of prior physical effort on the results of these tests remains poorly understood. The purpose of this study was to determine whether preceding physical effort can influence the outcome of concussion assessments. DESIGN: Prospective observational study. SETTING: University Medicine Center. PATIENTS: A cohort of 40 subjects (20 rugby players and 20 athletes from a range of sports). INTERVENTION: A concussion assessment was performed immediately after physical activity. After a period of 6 months and under the same experimental conditions, the same cohort performed the same tests in resting conditions. MAIN OUTCOME MEASURES: Results of concussion tests. RESULTS: In both cohorts, the comparison for postexercise and rest assessments demonstrated a most likely moderate-to-very large increase in the number of symptoms, severity of symptoms, and balance error scoring system score. In the rugby cohort, scores for concentration, delayed memory and standardized assessment of concussion (SAC), likely-to-most likely decreased following completion of physical activity compared with baseline values. The between-cohort comparison reported a most likely greater impact after exercise in the rugby players for delayed recall (0.73 ± 0.61) and SAC score (0.75 ± 0.41). CONCLUSIONS: Physical activity altered the results of concussion diagnostic tests in athletes from a range of sports and notably in rugby players. Therefore, physical efforts before the concussion incident should be accounted for during pitch-side assessments and particularly during rugby competition and training.

A governmental program to encourage medical students to deliver primary prevention: experiment and evaluation in a French faculty of medicine.

BACKGROUND: A public health student service was set up by the French government in 2018 with the aim of increasing awareness of primary health promotion among the 47,000 students of medicine and other health professions. It is an annual program involving community-based actions on nutrition, physical activity, addiction or sexuality. Our objective was to evaluate its implementation at local level and the different experiences of the stakeholders. METHODS: A quasi-experimental study using process evaluation was performed in a Faculty of Medicine in Paris. Quantitative and qualitative data were collected from medical students who carried out preventive health actions, in the institutions in which the actions took place and from a subsample of beneficiaries. RESULTS: One hundred and eight actions were carried out by 341 students in 23 educational or social institutions, mostly high schools (n = 12, 52%). Two thirds of the students did not feel sufficiently prepared to deliver preventive health interventions (65.7%, 224/341); however the beneficiaries found that the interventions were good (278/280, 99,2%). Nineteen (83%) of the host institutions agreed to welcome health service students again, of which 9 required some modifications. For students, the reporting of a satisfactory health service experience was associated with the reporting of skills or knowledge acquisition (p < 0.01). Delivering actions in high schools and to a medium-sized number of beneficiaries per week was associated with students' satisfaction. No effect of gender or theme of prevention was observed. For 248/341 (72.7%) students, the public health service program prompts them to address prevention issues in the future. CONCLUSION: The public health service undertaken by medical students through the program is a feasible and acceptable means of delivering preventive actions. Reinforcement of training and closer interaction with the host institutions would improve results.

Long-term consequences of recurrent sports concussion.

BACKGROUND: Recurrent concussions are suspected to promote the development of long-term neurological disorders. The study was designed to assess the prevalence of major depressive disorder, mild cognitive disorders and headache in a population of retired high-level sportsmen and rugby players and to study the link between scores evaluating these disorders and the number of reported concussions (RCs). METHODS: A total of 239 retired rugby players (RRPs) and 138 other retired sportsmen (ORSs) who had reached the French national or international championship level between 1985 and 1990 filled in a self-administered questionnaire describing their sociodemographic data, comorbidities and reported history of RC. A phone interview was then conducted using validated questionnaires for the detection of major depressive disorder (PHQ-9), mild cognitive disorders (F-TICS-m) and headache (HIT-6). RESULTS: RRPs reported a higher number of RCs than ORSs (p < 0.001). A higher rate of major depressive disorder (PHQ-9 score >9) was observed among RRPs compared to ORSs (9% versus 6%) (p = 0.04), and the PHQ-9 score increased with the number of RCs regardless of the type of sport (p = 0.026). A higher rate of mild cognitive disorders (TICS-m score ≤30) was observed in RRPs compared to ORSs (57% versus 40%, p = 0.005), but no association was found with the number of RC. The HIT-6 score increased with the number of RCs (p = 0.019) CONCLUSIONS: More than 20 years after the end of their career, RRPs present higher rates of depression and lower F-TICS-m scores in favor of mild cognitive impairment compared with ORSs. PHQ-9 and HIT-6 scores were significantly associated with the number of RCs.

The prevalence of IgG4-positive plasma cells in hypophysitis: a possible relationship to IgG4-related disease.

AIMS: Hypophysitis is a rare chronic inflammation of the pituitary gland corresponding currently to six histopathological subtypes. Among them, immunoglobulin- G4-related hypophysitis was recently added in this classification. The aim of this study was to perform a retrospective histopathological and immunohistochemical analysis to evaluate the prevalence of IgG4-related hypophysitis and review reported cases. METHODS: All samples of hypophysitis from Lariboisiere hospital were reviewed by two pathologists to assess their subtypes. An immunohistochemistry against IgG4 and IgG was performed. Slides were numerized, and IgG4-positive plasma cells and IgG plasma cells were counted in three high-power fields to evaluate the ratio. RESULTS: Eight cases were included: 5 lymphocytic hypophysitis, 1 granulomatous subtype, and 2 IgG4-related hypophysitis, affecting two young women without other coaffected organ. CONCLUSION: Our results show that IgG4-related hypophysitis is not an exceptional entity. Storiform fibrosis and obliterative phlebitis, histopathological characteristics of IgG4-related disease in other organs, are lacking in pituitary lesions. This study proves the interest of immunohistochemistry for diagnosis of IgG4-related hypophysitis. Due to the sensibility of IgG4-disease to steroids in other organs, this finding could be of clinical relevance.

The International Rugby Board (IRB) Pitch Side Concussion Assessment trial: a pilot test accuracy study.

BACKGROUND: 'On the field and on the run' assessments of head impact events in professional rugby have resulted in a high proportion of players subsequently diagnosed with confirmed concussion not leaving the field of play at the time of injury. The International Rugby Board (IRB) consequently developed a process to support team doctors in the recognition and management of players at risk of concussion, including development of a multimodal assessment instrument-the Pitch Side Concussion Assessment (PSCA) tool. METHODS: This was a pilot cohort study designed to determine the feasibility of assessing the accuracy of the IRB PSCA tool in elite male rugby. The study population comprised consecutive players identified with a head impact event with the potential to result in concussion during eight international/national competitions. Players were assessed off field by match-day or team doctors, following a temporary substitution. The accuracy of the PSCA tool was measured against a reference standard of postmatch confirmed concussion, based on clinical judgement aided by an established concussion support instrument. RESULTS: A total of 165 head injury events with the potential to cause concussion were included in the study. The PSCA tool demonstrated a sensitivity of 84.6% (95% CI 73.5% to 92.4%) and a specificity of 74% (95% CI 64.3% to 82.3%) to identify players subsequently diagnosed with confirmed concussion. The negative predictive value was 88.1% (95% CI 79.2% to 94.1%); the positive predictive value was 67.9% (95% CI 56.6% to 77.8%). There were no major barriers identified that would prevent the evaluation of the PSCA process or tool in a future large-scale study. CONCLUSIONS: This pilot study has provided the first preliminary estimates for the performance of the PSCA tool, suggesting a potentially favourable balance between positive and negative predictive values. The study has also offered a strong basis to conduct a further larger trial, providing information for sample size calculations and highlighting areas for methodological development.

3D mapping of cerebrospinal fluid local volume changes in patients with hydrocephalus treated by surgery: preliminary study.

OBJECTIVE: To develop automated deformation modelling for the assessment of cerebrospinal fluid (CSF) local volume changes in patients with hydrocephalus treated by surgery. METHODS: Ventricular and subarachnoid CSF volume changes were mapped by calculating the Jacobian determinant of the deformation fields obtained after non-linear registration of pre- and postoperative images. A total of 31 consecutive patients, 15 with communicating hydrocephalus (CH) and 16 with non-communicating hydrocephalus (NCH), were investigated before and after surgery using a 3D SPACE (sampling perfection with application optimised contrast using different flip-angle evolution) sequence. Two readers assessed CSF volume changes using 3D colour-encoded maps. The Evans index and postoperative volume changes of the lateral ventricles and sylvian fissures were quantified and statistically compared. RESULTS: Before surgery, sylvian fissure and brain ventricle volume differed significantly between CH and NCH (P = 0.001 and P = 0.025, respectively). After surgery, 3D colour-encoded maps allowed for the visual recognition of the CSF volume changes in all patients. The amounts of ventricle volume loss of CH and NCH patients were not significantly different (P = 0.30), whereas readjustment of the sylvian fissure volume was conflicting in CH and NCH patients (P < 0.001). The Evans index correlated with ventricle volume in NCH patients. CONCLUSION: 3D mapping of CSF volume changes is feasible providing a quantitative follow-up of patients with hydrocephalus. KEY POINTS: • MRI can provide helpful information about cerebrospinal fluid volumes. • 3D CSF mapping allows quantitative follow-up in communicating and non-communicating hydrocephalus. • Following intervention, fissures and cisterns readjust in both forms of hydrocephalus. • These findings support the hypothesis of suprasylvian block in communicating hydrocephalus. • 3D mapping may improve shunt dysfunction detection and guide valve pressure settings.

Imaging of the entire cerebrospinal fluid volume with a multistation 3D SPACE MR sequence: feasibility study in patients with hydrocephalus.

OBJECTIVES: To evaluate the feasibility of imaging the entire cerebrospinal fluid (CSF) volume using the SPACE MR sequence. METHODS: The SPACE sequence encompassing the brain and spine was performed at 1.5 T in 12 healthy volunteers and 26 consecutive patients with hydrocephalus. Image contrast was estimated using difference ratios in signal intensity between CSF and its background. Segmentation of CSF was performed using geometrical features and a topological assumption of CSF shapes. Subarachnoid and ventricular CSF space volumes were assessed in volunteers and patients and linear discriminant analysis was performed. RESULTS: Image contrast was 0.94 between the CSF and the brain and 0.90 between the CSF and the spinal cord. According to the phantom study, the accuracy of CSF volume measurement was 98.5 %. A clear distinction between patients and healthy volunteers was obtained using the linear discriminant analysis. Significant linear regression was found in healthy volunteers between ventricular (Vv) and the whole subarachnoid CSF volume (Vs) with Vv = 0.083 Vs. CONCLUSIONS: Imaging of the entire CSF volume is feasible in healthy volunteers and patients with hydrocephalus. CSF volume can be obtained on a whole-body scale. This approach may be of use for the diagnosis and follow-up of patients with hydrocephalus. KEY POINTS: • MRI assessment of CSF volume is feasible in healthy volunteers/hydrocephalus patients. • CSF volume can be obtained on a whole-body scale. • The ratio of subarachnoid and ventricular CSF is constant in healthy volunteers. • CSF linear discriminant analysis can distinguish between patients and healthy volunteers. • Entire CSF volume imaging is useful for diagnosing and following hydrocephalus.

Long-term neuromechanical results of selective tibial neurotomy in patients with spastic equinus foot.

BACKGROUND: The neuromechanical consequences of tibial neurotomy have not been extensively studied. METHODS: Fifteen patients were evaluated before and after selective tibial neurotomy (after 2 months and after 15 months) by means of clinical, neurophysiological [tendon (T) reflexes, Hoffmann (H) reflexes and maximum motor response, Mmax] and mechanical parameters (passive stiffness of plantar flexors at the ankle). The neurotomy concerned the soleus (100 % of cases), gastrocnemius (20 % of cases), posterior tibial (60 % of cases) and flexor digitorum longus (47 % of cases) nerves. RESULTS: Neurotomy provided more than 90 % improvement of clinical spasticity scores, 20 % improvement of walking scores and the angle of passive dorsiflexion (APDF) of the ankle (mean angle: 7°), temporary reduction of the soleus Mmax (18 % at 2 months with return to the preoperative value at 15 months), and lasting reduction of the soleus Hmax/Mmax (68 % at 2 months, 78 % at 15 months) and T/Mmax (84 % at 2 months, 80 % at 15 months). M and H responses of the gastrocnemius (whether or not they were included in the neurotomy) were not modified, while T/Mmax decreased to the same degree as for soleus. Passive stiffness was lastingly decreased from 64.0 Nm/rad to 49.0 Nm/rad (2 months) and 49.5 Nm/rad (15 months). CONCLUSION: Selective tibial neurotomy of the soleus nerve induces long-term reduction of reflex hyperexcitability and passive stiffness of plantar flexors in spastic patients, with no lasting impairment of motor efferents. In parallel, it modifies the tendon reflexes of synergistic muscles (gastrocnemius) not concerned by the neurotomy.

Time course of the soleus M response and H reflex after lidocaine tibial nerve block in the rat.

AIMS: In spastic subjects, lidocaine is often used to induce a block predictive of the result provided by subsequent surgery. Lidocaine has been demonstrated to inhibit the Hoffmann (H) reflex to a greater extent than the direct motor (M) response induced by electrical stimulation, but the timecourse of these responses has not been investigated. METHODS: An animal (rat) model of the effects of lidocaine on M and H responses was therefore developed to assess this time course. M and H responses were recorded in 18 adult rats before and after application of lidocaine to the sciatic nerve. RESULTS: Two to five minutes after lidocaine injection, M responses were markedly reduced (mean reduction of 44%) and H reflexes were completely abolished. Changes were observed more rapidly for the H reflex. The effects of lidocaine then persisted for 100 minutes. The effect of lidocaine was therefore more prolonged on the H reflex than on the M response. CONCLUSION: This study confirms that lidocaine blocks not only alpha motoneurons but also Ia afferent fibres responsible for the H reflex. The authors describe, for the first time, the detailed time course of the effect of lidocaine on direct or reflex activation of motoneurons in the rat.

Comparing the Effect of Implanted Peroneal Nerve Stimulation and Ankle-Foot Orthosis on Gait Kinematics in Chronic Hemiparesis: A Randomized Controlled Trial.

OBJECTIVE: Impaired ankle dorsiflexion in hemiparesis may be treated with ankle-foot orthosis or functional electrical stimulation. Semi-implanted selective functional electrical stimulation uses independent stimulations of deep and superficial peroneal nerves. The aim of this study was to compare gait kinematics using ankle-foot orthosis or semi-implanted selective functional electrical stimulation over 6 months in hemiparesis. METHODS: Subjects with chronic hemiparesis, randomized into ankle-foot orthosis or semi-implanted selective functional electrical stimulation groups, underwent comfortable gait analysis without and with device OFF and ON, before, and 3 and 6 months after treatment onset. The effects of condition, visit and group on gait kinematics (analysis of variance; ANOVA) were analysed. RESULTS: A total of 27 subjects were included (ankle-foot orthosis, n = 13; semi-implanted selective functional electrical stimulation, n = 14). The only between-group difference in changes from OFF to ON conditions was a deteriorated ankle dorsiflexion speed with ankle-foot orthosis at month 6 (condition*group, p = 0.04; ankle-foot orthosis, -60%, p = 0.02; semi-implanted selective functional electrical stimulation, non significant). Both groups pooled, from OFF to ON gait speed (+ 0.07 m/s; + 10%), cadence (+ 4%), step length (+ 6%) and peak ankle dorsiflexion (+ 6°) increased, and peak ankle inversion (-5°) and peak knee flexion (-2°) decreased (p < 0.001); finally, peak knee flexion in the OFF condition increased (+ 2°, p = 0.03). CONCLUSION: Semi-implanted selective functional electrical stimulation and ankle-foot orthosis similarly impacted gait kinematics in chronic hemiparesis after 6 months of use. Ankle dorsiflexion speed in swing deteriorated markedly with ankle-foot orthosis.

Blood Biomarkers for Return to Play after Concussion in Professional Rugby Players.

We prospectively evaluated a panel of seven blood biomarkers (S100 calcium-binding protein B [S100B], neuron specific enolase [NSE], spectrin breakdown products [SBDP], ubiquitin C-terminal hydrolase L1 [UCHL1], glial fibrillary acidic protein [GFAP], neurofilament light chain [NFL], and tubulin-associated unit [Tau]) for sport-related concussion (SRC) in a large multi-centric cohort of 496 professional rugby players from 14 French elite teams. Players were sampled twice during the season (beginning and end) away from any sport practice. From these two baseline samples, we evaluated the intra-individual variability to establish the effect of rugby on blood biomarkers over a season. Only S100B and GFAP remained stable over the course of a season. During the period of the study, a total of 45 SRC cases was reported for 42 players. In 45 SRCs, the head injury assessment (HIA) process was performed and blood collection was realized 36 h after the concussion (HIA-3 stage). For each biomarker, raw concentrations measured 36 h after SRC were not significantly different between players with a non-resolutive SRC (n = 28) and those with a resolutive SRC (n = 17; p between 0.06 and 0.92). In a second step, blood concentrations measured 36 h after SRC were expressed according to the basal concentrations as an individual percentage change (PCH36[%]), calculated as follows: PCH36 = 100 × (([Biomarker]36h - [Biomarker]basal)/[Biomarker]basal). S100B and NFL concentrations expressed as PCH36[%] were significantly different between non-resolutive and resolutive SRCs (p = 0.006 and 0.01 respectively), with a positive delta found in non-resolutive SRCs. Among the two biomarkers, it is important to note that only the S100B protein was stable during the season. In the context of our study, during HIA-3 assessment, S100B seems to perform better than NSE, SBDP, UCHL1, GFAP, NFL, and Tau as biomarker for SRC. From a clinical standpoint, the S100B modification over baseline may be valuable, at 36 h after concussion to distinguish non-resolutive SRC from resolutive SRC.

Accuracy of external ventricular drainage catheter placement.

BACKGROUND: External ventricular drainage (EVD) is a freehand neurosurgical procedure performed routinely using the anatomical landmarks. OBJECTIVE: The aim of this study was to determine the accuracy of EVD catheter freehand placement. MATERIALS AND METHODS: Pre-operative and post-operative computed tomography scans for 66 consecutive EVDs performed in 56 adult patients (26 men, 30 women) in 2008 were retrospectively reviewed. Etiologies of acute hydrocephalus were subarachnoid or intraventricular haemorrhage (43 cases) or miscellaneous (13 cases). Pre-operative lateral ventricular volume, position of the burr hole, length of the catheter and its sagittal and coronal angular variations from a theoretical trajectory were measured. RESULTS: The EVD was placed on the right (53 cases) or left (13 cases) side. The mean pre-operative lateral ventricular volume was 51 cc (10-118 cc). The average distance from the burr hole to the midline was 28 mm (10-49 mm) and to the supra-orbital ridge was 101 mm (75-125 mm). The mean intracranial catheter length was 60 mm (from 39-102 mm). Only 50% of the EVDs in the coronal plane and 40% in the sagittal plane were placed with an angular variation of ±5° to the target. The tip was placed outside of the ventricles in three cases; 13 catheters crossed the midline, and five intracranial minor haemorrhages were detected. CONCLUSION: Freehand placement of EVDs does not have sufficient accuracy and may lead to drainage dysfunctions. This data suggests that a guidance system for EVD's would be required.

Intracranial cerebrospinal fluid spaces imaging using a pulse-triggered three-dimensional turbo spin echo MR sequence with variable flip-angle distribution.

OBJECTIVE: To assess the three-dimensional turbo spin echo with variable flip-angle distribution magnetic resonance sequence (SPACE: Sampling Perfection with Application optimised Contrast using different flip-angle Evolution) for the imaging of intracranial cerebrospinal fluid (CSF) spaces. METHODS: We prospectively investigated 18 healthy volunteers and 25 patients, 20 with communicating hydrocephalus (CH), five with non-communicating hydrocephalus (NCH), using the SPACE sequence at 1.5T. Volume rendering views of both intracranial and ventricular CSF were obtained for all patients and volunteers. The subarachnoid CSF distribution was qualitatively evaluated on volume rendering views using a four-point scale. The CSF volumes within total, ventricular and subarachnoid spaces were calculated as well as the ratio between ventricular and subarachnoid CSF volumes. RESULTS: Three different patterns of subarachnoid CSF distribution were observed. In healthy volunteers we found narrowed CSF spaces within the occipital aera. A diffuse narrowing of the subarachnoid CSF spaces was observed in patients with NCH whereas patients with CH exhibited narrowed CSF spaces within the high midline convexity. The ratios between ventricular and subarachnoid CSF volumes were significantly different among the volunteers, patients with CH and patients with NCH. CONCLUSION: The assessment of CSF spaces volume and distribution may help to characterise hydrocephalus.

Incidence and Risk Factors in Concussion Events: A 5-Season Study in the French Top 14 Rugby Union Championship.

BACKGROUND: Concussions are a source of major concern in rugby, and a limited number of studies have attempted to identify risk factors for these injuries. PURPOSE: To investigate the incidence of match concussion and associated risk factors, including individual workload, anthropometric variables, playing position, and season phase, in elite rugby union players. STUDY DESIGN: Case-control study; Level of evidence 3. METHODS: All concussions and explanatory variables were collected for every match over 5 consecutive seasons (2014-2018) in 1334 professional players participating in the French Top 14 championship. Concussion risk was estimated using mixed effects Poisson regression. RESULTS: Mean match concussion incidence equated to 10.4 (95% CI, 9.3-11.5) concussions for 1000 hours of game exposure. A peak was reached in the 2016-2017 season (13.7; 95% CI, 11.0-16.5). A greater risk was observed in the playoffs as compared with the first phase of the season (incidence rate ratio, 3.96; 95% CI, 2.10-7.35). In comparison with other positions, half-backs incurred the highest rate of concussion events (incidence, 16.1; 95% CI, 11.8-20.3). Irrespective of playing position, those with greater height and lower body mass reported a higher risk of concussions (P = .02), especially during tackling actions for lighter players (P = .01) and during other match events for taller players (P = .03). When adjusted for season phase, players who had accumulated a higher amount of playing time since the beginning of the season demonstrated a lower risk of concussion (P = .005). CONCLUSION: Inter- and intraseasonal variations in concussion rates were observed. Within positional groups, lighter and taller players were more at risk, with the highest incidence generally observed in half-backs. Workload was measured by the number of matches played before a concussion event, and it appeared to have a protective rather than deleterious effect on concussion risk.