Evaluation of safety of fluoxetine for cerebellar mutism syndrome in children after posterior fossa surgery.

BACKGROUND: Cerebellar mutism syndrome (CMS) occurs in 8-29 % of children undergoing posterior fossa tumor surgery. Its main symptoms are mutism and emotional lability. Although it is always transient, recovery time can be lengthy with long-term cognitive sequelae. There is no approved drug treatment for CMS, but some drugs are used in everyday medical practice. One of these is fluoxetine, which has been used for many years in our institution. The main objective of this study was to establish the safety profile of fluoxetine in this condition. MATERIALS AND METHODS: The records of patients admitted to the pediatric intensive care unit after brain surgery at Angers University Hospital from 2010 to 2020 were reviewed. Children aged 2 years and older who underwent a posterior fossa tumor surgery and were diagnosed with CMS were included. Data on patient characteristics, prescription of fluoxetine treatment, side effects if any, and complete mutism duration were collected. RESULTS: Among 246 patients admitted to the pediatric intensive care unit for brain surgery during the study period, 23 had CMS and eight were prescribed fluoxetine. No serious adverse event related to fluoxetine was reported. Complete mutism duration did not differ significantly between the fluoxetine group and the non-fluoxetine group(p = 0.22). However, the treatment was initiated after recovery from complete mutism in half of the treated patients. CONCLUSION: This study suggests a positive safety profile of fluoxetine used in postoperative CMS. It does not answer the question of whether the treatment is effective for this indication. A randomized controlled trial based on a syndrome severity scale should be conducted to provide a more reliable assessment of the efficacy and safety of fluoxetine.

Metameric pruritus as the sole manifestation of an intramedullary tumor in a toddler.

An 18-month-old child presented with persistent pruritus and excoriation involving the right T9 and T10 dermatomes. She did not exhibit any other dermatological or neurological anomalies. Based on magnetic resonance imaging investigation of the spine, T8 ganglioglioma was diagnosed and surgically removed resulting in resolution of the pruritus within a few days. This observation underlines the importance of neuroimaging in patients presenting with metameric pruritus without specific skin lesions, especially in young children.

Chiari malformation type I surgery in children: French multicenter 10-year cohort.

OBJECTIVE: Chiari malformation type I (CM-I) is frequent in children and remains a surgical challenge. Several techniques have been described for posterior fossa decompression. No decision algorithm has been validated, and strategies are highly variable between institutions. The goal of this study was to define therapeutic guidelines that take into consideration patient specificities. METHODS: The authors retrospectively collected data from patients who were < 18 years of age, were diagnosed with CM-I, and were treated surgically between 2008 and 2018 in 8 French pediatric neurosurgical centers. Data on clinical features, morphological parameters, and surgical techniques were collected. Clinical outcomes at 3 and 12 months after surgery were assessed by the Chicago Chiari Outcome Scale. The authors used a hierarchical clustering method to define clusters of patients by considering their anatomical similarities, and then compared outcomes between surgical strategies in each of these clusters. RESULTS: Data from 255 patients were collected. The mean age at surgery was 9.6 ± 5.0 years, syringomyelia was reported in 60.2% of patients, the dura mater was opened in 65.0% of patients, and 17.3% of patients underwent a redo surgery for additional treatment. The mean Chicago Chiari Outcome Scale score was 14.4 ± 1.5 at 3 months (n = 211) and 14.6 ± 1.9 at 12 months (n = 157). The hierarchical clustering method identified three subgroups with potentially distinct mechanisms underlying tonsillar herniation: bony compression, basilar invagination, and foramen magnum obstruction. Each cluster matched with specific outcomes. CONCLUSIONS: This French multicenter retrospective cohort study enabled the identification of three subgroups among pediatric patients who underwent surgery for CM-I, each of which was associated with specific outcomes. This morphological classification of patients might help in understanding the underlying mechanisms and providing personalized treatment.

Collateral effects of targeting the nucleus pulposus via a transpedicular or transannular surgical route: a combined X-ray, MRI, and histological long-term descriptive study in sheep.

PURPOSE: In the context of regenerative medicine strategies, based in particular on the injection of regenerative cells, biological factors, or biomaterials into the nucleus pulposus (NP), two main routes are used: the transpedicular approach (TPA) and the transannular approach (TAA). The purpose of our study was to compare the long-term consequences of the TPA and the TAA on intervertebral disc (IVD) health through a longitudinal follow-up in an ovine model. METHODS: The TPA and the TAA were performed on 12 IVDs from 3 sheep. Six discs were left untreated and used as controls. The route and injection feasibility, as well as the IVD environment integrity, were assessed by MRI (T2-weighted signal intensity), micro-CT scan, and histological analyses (Boos' scoring). The sheep were assessed at 1, 3, and 7 months. RESULTS: Both the TPA and the TAA allowed access to the NP. They both induced NP degeneration, as evidenced by a decrease in the T2wsi and an increase in the Boos' scores. The TPA led to persistent end-plate defects and herniation of NP tissue (Schmorl's node-like) after 7 months as well as the presence of osseous fragments in the NP. CONCLUSIONS: The TPA induced more severe lesions in IVDs and vertebrae compared to the TAA. The lesions induced by the TPA are reason to consider whether or not this route is optimal for studying IVD regenerative medicine approaches.

Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): Clinical, radiological and pathological characteristics in a French series.

BACKGROUND: Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics. METHODS: In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology. RESULTS: Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies. CONCLUSIONS: The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.

Sustained Response and Rationale of Programmed Cell Death-1-Targeting for Progressive Multifocal Leukoencephalopathy.

In this study, we report a complete (clinical, radiological, and virological) sustained (1 year) response after nivolumab salvage therapy in a progressive multifocal leukoencephalopathy patient. Analyses of the cells infiltrate in a pretreatment brain biopsy suggest that parenchymal programmed cell death-L1+ macrophages could be the T-cells partnership in immune exhaustion and virus escape.

The transpedicular surgical approach for the development of intervertebral disc targeting regenerative strategies in an ovine model.

PURPOSE: To investigate the suitability of the transpedicular approach (TPA) in a sheep model of IVD regenerative strategies METHODS: 24 IVD from four sheep were used. TPA and biopsies of the Nucleus pulposus (NP) were performed in 18 IVD (6 IVD control). Seven discographies were performed to assess the feasibility of injecting contrast agent. MRI, micro-CT scan, and histological analyses were performed and the accuracy of the TPA was evaluated. The effects on the vertebra and endplates were analyzed. RESULTS: 83% of our biopsies or injections were located in the NP. Osseous fragments in IVD were observed in 50%. We observed two cases (11%) of rostral endplate fracture and five cases (27%) of breaching of the cortical pedicle and encroachment into the spinal canal. Two cases of perivertebral venous embolism and two of backflow through the canal of the TPA inside the vertebra were noted. Significant damage occurred to the bone structure of the vertebra and to the rostral endplate on which the IVD had been inserted. CONCLUSIONS: TPA induces damage to the endplates, and it may lead to neurological impairment and leakage of injected materials into the systemic circulation. These adverse effects must be fully considered before proceeding with TPA for IVD regenerative strategies.

Management of hydrocephalus in pediatric metastatic tumors of the posterior fossa at presentation.

PURPOSE: Presence of metastases in newly diagnosed pediatric posterior fossa tumors (PFT) is not a rare situation, but optimal treatment of associated hydrocephalus in these children has remained undetermined. METHODS: Twenty-nine children treated between January 2005 and December 2015 for a metastatic PFT associated with hydrocephalus constituted the study cohort. Patients were divided into three groups: ventriculoperitoneal shunt (VPS), endoscopic third ventriculostomy (ETV), and temporary ventricular drainage before or during tumor resection (PVD). RESULTS: There were 4 VPS, 18 ETV, and 7 PVD. The global incidence of CSF diversion failure was 52%. No case of dysfunction or dissemination of metastatic cells occurred in the VPS group. Recurrence of hydrocephalus occurred in 55% of the ETV group. Presence of multiple macroscopic metastases and CSF metastatic cells after tumor surgery was associated with ETV failure. Fifty-seven percent of the children in the PVD group were reoperated after an average time of 53 days. Specific oncologic treatment was initiated earlier in the VPS group (11 days) compared to ETV (27 days) and PVD (23 days) groups. CONCLUSIONS: ETV should be avoided in cases of multiple macroscopic metastases, and children who underwent ETV must be followed carefully when metastatic cells are present in CSF after tumor surgery. External ventricular drainage before or during surgical removal should not be considered as a final option to treat hydrocephalus. VPS remains a safe alternative in this situation and allows an early specific oncologic treatment.

Mild head injury and attention deficit hyperactivity disorder in children.

PURPOSE: Post-concussion syndrome is a well-described complication following moderate and severe head trauma but whether it occurs after mild head injury in children remains unclear. The aim of this study was to evaluate whether exposure to mild head injury with potential additional risk factors (non-surgical lesion on computed tomographic, high kinetic trauma, or Glasgow Coma Scale <15) is associated with attention deficit hyperactivity disorder (ADHD) after the head trauma. METHODS: This study was performed in an emergency department on children admitted between 2009 and 2013. It compared victims of mild head injury aged 6-16 years with matched children presenting isolated non-surgical forearm fracture (ratio1/2). ADHD was assessed using Conners' Global Index-Parent short version 3-40 months after the trauma. The patients were compared using chi-square test or Fisher's exact test, t test or u-test as appropriate with a p value set at 0.05. RESULTS: During the study period, 676 patients were admitted for mild head injury. Among them, 34 (5 %) fulfilled the inclusion criteria and were compared with 64 matched patients admitted for a forearm fracture. The groups were comparable. ADHD was observed in both groups (18 % in the mild head injury group, 11 % in the control group) with no significant differences between groups. The prevalence was high when compared to an expected frequency of 3.5-5.6 % in children aged 6-12 years in the general population. CONCLUSIONS: These results suggest that pre-existing ADHD may have contributed to injury proneness in both groups and does not argue for a specific risk of ADHD induced by mild head injury. The diagnosis of ADHD should be evoked at admission of children aged 6-16 years presenting with a trauma.

Intradiploic growing skull fracture: review of mechanisms and literature.

PURPOSE: A rare case of intradiploic growing fracture of the occipital bone is presented. Examination of this case and literature review was carried out to find significant specific features of such a rare condition. CASE: A 4-year-old boy was operated on for a huge occipital intradiploic growing skull fracture. His medical history, surgical management, and postoperative course are presented. LITERATURE REVIEW: A computer literature search using the Medline database revealed 31 well-documented cases. CONCLUSIONS: Special attention must be paid to skull fractures in childhood when occurring near CSF large spaces, especially if ventricle enlargement, suggesting that hydrocephalus is present. Surgeons should evaluate hydrocephalus before treating such lesions in order to improve surgical result and postoperative clinical evolution.

Pore formation in a lipid bilayer under a tension ramp: modeling the distribution of rupture tensions.

The rupture of fluid membrane vesicles with a steady ramp of micropipette suction has been shown to produce a distribution of breakage tensions, with a mean that rises rapidly with tension rate. Starting from a lattice model that incorporates the essential features of the lipid bilayers held together with hydrophobic forces, and developing it to handle varying tension rates, we reproduce the main features of the experimental results. In essence, we show that the rupture kinetics are driven by the nucleation and growth of pores, with two limiting kinetics-growth-limited and nucleation-limited. The model has been extended to address the role of peptides in solution that can adsorb and insert themselves into the bilayer. At concentrations below those required to spontaneously rupture the membrane, the effect of the peptides is to lower the rupture tensions systematically for all tension rates.

Atypical pattern of acute severe shoulder pain: contribution of sonography.

A patient presented with an atypical pattern of acute severe shoulder pain. Sonography elucidated the mechanism of the pain and allowed effective treatment. The patient was unable not only to move her shoulder but also to flex and to extend her elbow. Sonography showed a calcific deposit in the subscapularis tendon with local edema displacing the long head of the biceps tendon out of the bicipital groove. Local injection of a glucocorticoid under ultrasonographic control was followed within 7 days by subsidence of the subscapularis tendon edema and by a return of the long head of the biceps tendon to its normal position in the bicipital groove.

Factors associated with early-stage pulmonary fibrosis as determined by high-resolution computed tomography among persons occupationally exposed to asbestos.

OBJECTIVES: Asbestosis remains difficult to diagnose, particularly in its early stages. The aim of this study was to determine criteria for independently associated features of pulmonary fibrosis in high-resolution computed tomograms among persons occupationally exposed to asbestos. METHODS: Retired persons with documented occupational asbestos exposure and no known asbestos-related diseases were assessed for occupational, clinical, functional respiratory, and chest X-ray criteria. In addition, they all underwent high-resolution computed tomography (HRCT) in the prone position. RESULTS: Altogether 51 (7.2%) of the 706 enrolled participants had features of pulmonary fibrosis consistent with asbestosis in the HRCT. Among those with small irregular opacities of <1/0 according to the 1980 International Labour Office Classification (ILO-C) in their X-rays, 5% had asbestosis in the HRCT. In a multivariate analysis, only age [odds ratio (OR) per year 1.08, 95% confidence interval (95% CI) 1.02-1.14], cumulative-exposure index (CEI) for asbestos (OR 6.4, 95% CI 1.5-28.4 for a CEI of > or =100 fibers/ml x years), and the presence of small irregular X-ray opacities of > or =1/0 ILO-C (OR 3.0, 95% CI 1.6-6.0) were independently associated with HRCT asbestosis. No combinations of these criteria simultaneously yielded high sensitivity and specificity for the diagnosis of early-stage HRCT asbestosis. Moreover, only 2% of the persons with a CEI of <25 fibers/ml x years had HRCT asbestosis, the finding confirming the low incidence of asbestosis for such low exposure, as previously reported on the basis of X-ray data. CONCLUSIONS: Additional research is needed to better identify the persons most likely to benefit from HRCT screening for asbestosis.

Lattice model for the kinetics of rupture of fluid bilayer membranes.

We have constructed a model for the kinetics of rupture of membranes under tension, applying physical principles relevant to lipid bilayers held together by hydrophobic interactions. The membrane is characterized by the bulk compressibility (for expansion) K, the thickness 2h(t) of the hydrophobic part of the bilayer, the hydrophobicity sigma, and a parameter gamma characterizing the tail rigidity of the lipids. The model is a lattice model which incorporates strain relaxation, and considers the nucleation of pores at constant area, constant temperature, and constant particle number. The particle number is conserved by allowing multiple occupancy of the sites. An equilibrium "phase diagram" is constructed as a function of temperature and strain with the total pore surface and distribution as the order parameters. A first-order rupture line is found with increasing tension, and a continuous increase in protopore concentration with rising temperature till instability. The model explains current results on saturated and unsaturated phosphatidylcholine lipid bilayers and thicker artificial bilayers made of diblock copolymers. Pore size distributions are presented for various values of area expansion and temperature, and the fractal dimension of the pore edge is evaluated.