A Comprehensive Training Model for Simulation of Intracranial Aneurysm Surgery Using a Human Placenta and a Cadaveric Head.

BACKGROUND AND OBJECTIVES: Aneurysmal surgery is technically complex, and surgeon experience is an important factor in therapeutic success, but training young vascular neurosurgeons has become a complex paradigm. Despite new technologies and simulation models, cadaveric studies still offer an incomparable training tool with perfect anatomic accuracy, especially in neurosurgery. The use of human placenta for learning and improving microsurgical skills has been previously described. In this article, we present a comprehensive simulation model with both realistic craniotomy exposure and vascular handling consisting of a previously prepared and perfused human placenta encased in a human cadaveric specimen. METHODS: Humans' placentas from the maternity and cadaveric heads from the body donation program of the anatomy laboratory were used. Placentas were prepared according to the established protocol, and aneurysms were created by catheterization of a placental artery. Ten participants, including senior residents or young attendees, completed an evaluation questionnaire after completing the simulation of conventional unruptured middle artery aneurysm clipping surgery from opening to closure. RESULTS: The skin incision, muscle dissection, and craniotomy were assessed as very similar to reality. Brain tissue emulation and dissection of the lateral fissure were judged to be less realistic. Vascular management was evaluated as similar to reality as closure. Participants uniformly agreed that this method could be implemented as a standard part of their training. CONCLUSION: This model could provide a good model for unruptured aneurysm clipping training.

Reossification of Bone Defects After Surgical Correction of Nonsyndromic Craniosynostosis: A Review and An Original Study.

BACKGROUND AND OBJECTIVES: Surgical correction of nonsyndromic craniosynostosis (NSC) aims to restore cranial shape. Reossification of bone defects is paramount for the best aesthetic prognosis. However, the literature on the quantitative evaluation of bone defects after NSC surgery is scarce. This study aimed to quantify and analyze the surface area of bone defects after NSC surgery and establish a threshold value for predicting persistent defects. METHODS: We conducted a systematic review and a prospective study of 28 children undergoing surgical treatment for NSC. We analyzed 426 defects on the first computed tomography scan (1 year postoperative) and 132 defects on the second computed tomography scan (4.6 years postoperative). Statistical analysis was performed using Spearman's rank correlation coefficient, Mann-Whitney-Wilcoxon rank-sum test, and Youden's J statistic. RESULTS: Our systematic review identified three studies reporting on bone defects' surface area and reossification rate. In our study, we found no statistically significant differences in the number or size of defects between sex or type of NSC. The threshold value for the surface area of bone defects above which there was a higher probability of persistent defects was 0.19 cm2 (Youden point), with an 89.47 % probability of persistence. Defects with a surface area below 0.19 cm2 had a considerably lower probability, only 15.07%, of persistence over time. CONCLUSION: Our study provides valuable quantitative data for managing bone defects after NSC surgery. Defects with a surface area above 0.19 cm2 should be monitored with radiological imaging because of the risk of persistence. Our findings highlight the importance of developing robust and reproducible methods for the quantitative analysis of bone defects after NSC surgery.

Determinants of Return to Work After a Stroke: A Systematic Review and Meta-analysis.

OBJECTIVE: To identify prognostic factors for return to work (RTW) after stroke. DATA SOURCES: PubMed, MEDLINE, Cochrane, and Embase were systematically searched. STUDY SELECTION: Studies had to include people of working age (<65 years old) at the time of stroke (ischemic, hemorrhagic, or subarachnoid hemorrhage). The evaluation of RTW and rate of RTW had to be mentioned. Study selection was done by 2 independent authors. In total, 1241 articles were screened, 39 met all inclusion criteria. DATA EXTRACTION: Characteristics of included studies were recorded independently by 2 authors. Differences were resolved through discussion or with a third author. Quality was assessed using the Scottish Intercollegiate Guidelines Network quality assessment tool. DATA SYNTHESIS: Among the 39 studies, prognostic factors for RTW were hemorrhagic stroke (odds ratio 0.53 [95% confidence interval 0.45-0.60], n=18 studies), sex (men) (1.26 [1.14-1.40], n=31), aphasia (0.37 [0.20-0.69], n=7), occupation (white collar worker) (1.84 [1.64-2.06], n=17), independence in activities of daily living (3.99 [1.73-9.23], n=7), and stroke severity (NIHSS) (1.23 [1.08-1.39], n=6). CONCLUSIONS: This meta-analysis highlighted positive and negative prognostic factors associated with RTW after stroke. Two categories were distinguished: modifiable and non-modifiable prognostic factors. This study provides information to help understand the issues, set appropriate objectives and implement appropriate strategies to guide people to RTW after stroke. Randomized controlled studies are needed to better evaluate work-place intervention programs as well as the effects of intravenous thrombolysis, and cognitive and neuropsychological rehabilitation on return-to-work rates after stroke.

Vertebroplasty versus bracing in acute vertebral compression fractures: A prospective randomized trial.

BACKGROUND: The treatment of stable vertebral compression fractures remains controversial. OBJECTIVE: To compare the efficacy of vertebroplasty and bracing for acute vertebral compression fractures. METHODS: We conducted a prospective, randomized, non-blinded, single-center study. Adult participants were randomized to undergo vertebroplasty or bracing. Both groups were stratified by age. The primary outcome was functional disability (Roland-Morris disability questionnaire [RMDQ]). Secondary outcomes were pain intensity (Visual Analogue Scale [VAS]), and change in vertebral body height and kyphosis angle. Outcomes were assessed on day 2, and 1, 3 and 6 months after treatment. RESULTS: Ninety-nine people were included, 51 in the vertebroplasty group and 48 in the brace group. Treatment was performed within 2 weeks of the trauma. On day 2 post-treatment, pain was lower in the vertebroplasty group (mean [SD] 2.3 [1.5] versus 3.4 [2.1], p = 0.004) but the difference was no longer significant at 6 months. Functional disability was significantly lower in the vertebroplasty than brace group at all time-points (RMDQ score 7.5 [5.7] vs 11.4 [5.3], p<0.001 at 1 month). At 6 months, the increase in kyphosis angle was smaller in the vertebroplasty than the brace group (+1.5°versus +4°, p<0.001). CONCLUSION: In people with acute vertebral compression fractures, the immediate effect of vertebroplasty was greater than that of bracing on pain and function, and for restoring sagittal balance. At 6 months, the superiority of vertebroplasty decreased, except for the maintenance of sagittal balance. DATABASE REGISTRATION: ClinicalTrials.gov number, NCT01643395.

A rare complication of flow diverter: delayed migration causing aneurysm expansion and brainstem compression.

Flow-diverting stents (FD) are admitted therapeutic devices for challenging aneurysms. Delayed migrations of FD remain exceptional, particularly with brainstem compression. We report a case of delayed migration of pipeline embolization device (PED) responsible of medulla oblongata compression due to expansion of posterior inferior cerebellar artery (PICA) aneurysm. This is the first report of brainstem compression due to delayed migration of FD. Among the seven previously reported cases of FD delayed migration, two led to death. Our case illustrates the importance of technical issues of stenting and the role of surgery facing the clinical emergency of vascular compression of lower brainstem. We wanted to warn neurosurgeons of this rare and delayed complication, which likely could become less exceptional with the increase of indications and utilizations of FD.

Mechanical Complications of Sophysa SM8 Shunt in Adult Hydrocephalus: A Monocentric Experience.

BACKGROUND: Sophysa SM8 is widely used by neurosurgeons in France. Published studies report shunt malfunction rates in adults between 18% and 29%. However, these studies included multiple valve types and thus entailed a serious confounding factor. OBJECTIVE: To ascertain the incidence the Sophysa SM8 cerebrospinal fluid (CSF) shunt malfunctions in adults. METHODS: We present a retrospective series of adult patients who underwent CSF shunt placement between 2000 and 2013 with Sophysa SM8. RESULTS: In total, 599 patients (329 males and 270 females) were included. The mean age at surgery was 64.15 years (19-90) (SD 16.17; median 68.0). The causes of hydrocephalus were normal pressure hydrocephalus (49%), traumatic hemorrhages (26.5%), tumors (15.7%), cerebral aqueduct stenoses (3%), and arachnoid cysts (2%). The mean follow-up was 3.9 years (0-16) (SD 4.10; median 3 years). The rate of complications was 22.04% (132 of 599). Most frequent causes of complications were disconnection (25%), migration (12.9%), overdrainage (9.1%), and proximal obstruction (6.8%). In 17 cases (12.9%), no failure was diagnosed during revision. Seven infections (5.3%) were reported. The mean delay for the first revision was 1.70 years (0-13.93) (SD 2.67, median 0.35). The risk of shunt failure was 36% at 10 years. Seventeen percent of revisions occurred during the first year after shunt placement. CONCLUSION: Disconnections are a very frequent complication of Sophysa SM8 valve. They are related to the 2-connector system of this valve. Based on these results, we recommend using 1-piece valves.

Mechanical complications of cerebrospinal fluid shunt. Differences between adult and pediatric populations: myths or reality?

OBJECTIVE: Shunt malfunctions seem more frequent in children (44 to 81%) than in adults (18 to 29%). Because of discrepancies between studies, it is not possible to affirm this disparity. The objective was to verify whether the incidence of cerebrospinal fluid (CSF) shunt malfunctions is higher in children than adults. METHODS: We present a retrospective series of child and adult patients who underwent CSF shunt placement between 2000 and 2013 with a Sophysa SM8® valve. RESULTS: 599 adults and 98 children (sex ratio 1.28) underwent CSF shunt placement. Age at first surgery ranged between 1 day of life and 90 years (mean of 55.8 years, SD 25.8, median 64.8 years). The mean follow-up was 4 years (SD 4.264, 0-16; median 3 years). The cumulative complication rate was 25.5% (178/697). Mechanical complications were disconnection (25.1%), migration (11.8%), intracranial catheter obstruction (8.9%) and malposition (8.4%). The mean delay for the first revision was 1.90 years (0-13.9), (SD 2.73, median 0.5). The probability of shunt failure was 65% at 10 years in the child group and 36% at 10 years in the adult group. Moreover, in the child group, 33% of revisions occurred during the first year after shunt placement versus 17% in the adult group. Thus, the probability of shunt failure was higher in children than in adults (log-rank test, p < 0.001). CONCLUSIONS: This is the first retrospective study, comparing children and adults undergoing CSF shunt using the same valve, able to confirm the higher rate of complications in children.

Resolution of isolated syringomyelia after removing thoracic disc herniation.

Syringomyelia is an abnormal cystic dilatation of the spinal cord caused by excessive accumulation of CSF (cerebrospinal fluid). The pathophysiology remains complex and unelucidated. We report a rare case of resolution of cervico-thoracic syringomyelia after thoracic disc excision in a 3 months follow-up time.

MRI Atlas of the Human Deep Brain.

Mastering detailed anatomy of the human deep brain in clinical neurosciences is challenging. Although numerous pioneering works have gathered a large dataset of structural and topographic information, it is still difficult to transfer this knowledge into practice, even with advanced magnetic resonance imaging techniques. Thus, classical histological atlases continue to be used to identify structures for stereotactic targeting in functional neurosurgery. Physicians mainly use these atlases as a template co-registered with the patient's brain. However, it is possible to directly identify stereotactic targets on MRI scans, enabling personalized targeting. In order to help clinicians directly identify deep brain structures relevant to present and future medical applications, we built a volumetric MRI atlas of the deep brain (MDBA) on a large scale (infra millimetric). Twelve hypothalamic, 39 subthalamic, 36 telencephalic, and 32 thalamic structures were identified, contoured, and labeled. Nineteen coronal, 18 axial, and 15 sagittal MRI plates were created. Although primarily designed for direct labeling, the anatomic space was also subdivided in twelfths of AC-PC distance, leading to proportional scaling in the coronal, axial, and sagittal planes. This extensive work is now available to clinicians and neuroscientists, offering another representation of the human deep brain ([https://hal.archives-ouvertes.fr/] [hal-02116633]). The atlas may also be used by computer scientists who are interested in deciphering the topography of this complex region.

Pulse generator battery life in deep brain stimulation: out with the old in with the less durable?

BACKGROUND: Battery life of the most commonly used implantable pulse generators in deep brain stimulation is limited. Device replacement is costly and may expose patients to additional risks. Driven by the observation that in our experience newer generation devices seemed to need earlier replacement than the older generation, we aimed to retrospectively analyze the battery life of two generations of non-rechargeable devices, manufactured by a single company (Medtronic, USA). METHODS: Battery life of 281 devices in 165 patients was taken into account for data analysis. This represented 243 older generation devices (Kinetra and Soletra) and 38 newer generation devices (Activa). RESULTS: The battery life of older generation stimulators was 2-fold longer than the newer generation. CONCLUSIONS: Newer devices are more versatile than the older generation. Their battery life is however significantly shorter. Development of next-generation devices needs to address this issue in order to limit health risks and reduce financial costs.

Deep brain stimulation in five patients with severe disorders of consciousness.

OBJECTIVE: The efficacy of deep brain stimulation in disorders of consciousness remains inconclusive. We investigated bilateral 30-Hz low-frequency stimulation designed to overdrive neuronal activity by dual pallido-thalamic targeting, using the Coma Recovery Scale Revised (CRS-R) to assess conscious behavior. METHODS: We conducted a prospective, single center, observational 11-month pilot study comprising four phases: baseline (2 months); surgery and titration (1 month); blind, random, crossover, 1.5-month ON and OFF periods; and unblinded, 5-month stimulation ON. Five adult patients were included: one unresponsive-wakefulness-syndrome male (traumatic brain injury); and four patients in a minimally conscious state, one male (traumatic brain injury) and three females (two hemorrhagic strokes and one traumatic brain injury). Primary outcome measures focused on CRS-R scores. Secondary outcome measures focused notably on baseline brain metabolism and variation in activity (stimulation ON - baseline) using normalized fluorodeoxyglucose positron emission tomography maps. Statistical analysis used random-effect models. RESULTS: The two male patients (one minimally conscious and one unresponsive wakefulness syndrome) showed improved mean CRS-R scores (stimulation ON vs. baseline), in auditory, visual and oromotor/verbal subscores, and visual subscores respectively. The metabolism of the medial cortices (low at baseline in all five patients) increased specifically in the two responders. INTERPRETATION: Our findings show there were robust but limited individual clinical benefits, mainly in visual and auditory processes. Overall modifications seem linked to the modulation of thalamo-cortico-basal and tegmental loops activating default mode network cortices. Specifically, in the two responders there was an increase in medial cortex activity related to internal awareness.

Pattern of Closure of Skull Base Synchondroses in Crouzon Syndrome.

BACKGROUND: The age of closure of skull base synchondroses has never been analyzed in a homogenous population of children with Crouzon syndrome. METHODS: A retrospective case-control study was performed on 30 Crouzon children (17 male, 13 female) aged 1 month to 12.48 years with Fibroblast Growth Factor Receptor type 2 mutation. Eleven synchondroses were analyzed on millimetric computed tomodensitometric slices before surgery. Syndromic patients were compared with a series of 235 healthy children previously published. RESULTS: Synchondrosis closure follows a global pattern that occurs earlier in Crouzon syndrome than in controls (P ≤ 0.002). Synchondrosis fusion starts at 10 months of age with posterior intraoccipital synchondroses and lambdoid sutures, followed by occipitomastoid synchondroses between 1.85 (right) and 2.27 years (left) and anterior intraoccipital synchondroses at approximately 2.80 years. Time to complete fusion varies considerably according to the synchondroses. Spheno-occipital and petro-occipital synchondroses fuse last, at approximately 3 years old. CONCLUSIONS: In children with Crouzon syndrome, synchondrosis closure occurs prematurely, with a time course specific to each synchondrosis.

Assessment of citalopram and escitalopram on neuroblastoma cell lines. Cell toxicity and gene modulation.

Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (p<2.26 10-7), -24.1 (p<5.6 10-9) and -17.7 (p<1.2 10-7). CCNE1, AURKA, IGF2, MYCN and ERBB2 were more moderately down-regulated by both molecules. Glioma markers E2F1, DAPK1 and CCND1 were down-regulated. Citalopram displayed more powerful action with broader and distinct spectrum of action than escitalopram.

Subthalamus stimulation in Parkinson disease: Accounting for the bilaterality of contacts.

BACKGROUND: Deep brain stimulation (DBS) in Parkinson's disease uses bi-hemispheric high-frequency stimulation within the subthalamus, however, the specific impacts of bilaterality of DBS are still not clear. Thus, we aimed to study the individual-level clinical impact of locations of right-left contact pair-up accounting for each subthalamic nucleus (STN) anatomy. METHODS: Contact locations and effects at 1 year were studied retrospectively in an unselected series of 53 patients operated between 2004 and 2010. Location of contacts was defined relatively to the main axis of STN used to map longitudinal and transversal positions, and STN membership (out meaning out-of-STN). Contact pairings were described via three methods: (i) Unified contact location (UCL) collapsing DBS into an all-in-one contact; (ii) balance of contact pair-up (BCPU), defined as symmetric or asymmetric regardless of laterality; (iii) hemisphere-wise most frequent contact pair-up (MFCP) regardless of BCPU. Clinical data were: mean levodopa equivalent dose, Unified Parkinson's Disease Rating Scale (UPDRS) motor score III without medication, UPDRS II and III speech sub-scores, UPDRS II freezing sub-score, 1 year versus preoperative values, with and without levodopa. Ad-hoc two-sided tests were used for statistical analysis. RESULTS: Worsening speech, was more frequent for UCL_out patients and when the left MFCP contact was rear and/or superolateral, however, it less frequent for BCPU-asymmetric patients. Worsening freezing was more frequent when the right MFCP contact was rear and superolateral. CONCLUSIONS: These results point to strategies for minimizing dysarthria and freezing as adverse effects of DBS.

Human Foramen Magnum Area and Posterior Cranial Fossa Volume Growth in Relation to Cranial Base Synchondrosis Closure in the Course of Child Development.

BACKGROUND: To date, no study has compared the evolution of the foramen magnum area (FMA) and the posterior cranial fossa volume (PCFV) with the degree of cranial base synchondrosis ossification. OBJECTIVE: To illustrate these features in healthy children. METHODS: The FMA, the PCFV, and the ossification of 12 synchondroses according to the Madeline and Elster scale were retrospectively analyzed in 235 healthy children using millimeter slices on a computed tomography scan. RESULTS: The mean FMA of 6.49 cm in girls was significantly inferior to the FMA of 7.67 cm in boys (P < .001). In both sexes, the growth evolved in a 2-phase process, with a phase of rapid growth from birth to 3.75 years old (yo) followed by a phase of stabilization. In girls, the first phase was shorter (ending at 2.6 yo) than in boys (ending at 4.33 yo) and proceeded at a higher rate. PCFV was smaller in girls (P < .001) and displayed a biphasic pattern in the whole population, with a phase of rapid growth from birth to 3.58 yo followed by a phase of slow growth until 16 yo. In girls, the first phase was more active and shorter (ending at 2.67 yo) than in boys (ending at 4.5 yo). The posterior interoccipital synchondroses close first, followed by the anterior interoccipital and occipitomastoidal synchondroses, the lambdoid sutures simultaneously, then the petro-occipital and spheno-occipital synchondroses simultaneously. CONCLUSION: The data provide a chronology of synchondrosis closure. We showed that FMA and PCFV are constitutionally smaller in girls at birth (P ≤ .02) and suggest that a sex-related difference in the FMA is related to earlier closure of anterior interoccipital synchondroses in girls (P = .01). ABBREVIATIONS: AIOS, anterior interoccipital synchondrosesFMA, foramen magnum areaLS, lambdoid suturesOMS, occipitomastoidal synchondrosesPCFV, posterior cranial fossa volumePIOS, posterior interoccipital synchondrosesPOS, petro-occipital synchondrosesSOS, spheno-occipital synchondrosisyo, years old.

Anatomy of the Spinal Meninges.

BACKGROUND: The spinal meninges have received less attention than the cranial meninges in the literature, although several points remain debatable and poorly understood, like their phylogenesis, their development, and their interactions with the spinal cord. Their constancy among the chordates shows their crucial importance in central nervous system homeostasis and suggests a role far beyond mechanical protection of the neuraxis. OBJECTIVE: This work provides an extensive study of the spinal meninges, from an overview of their phylogenesis and embryology to a descriptive and topographic anatomy with clinical implications. It examines their involvement in spinal cord development, functioning, and repair. METHODS: This work is a review of the literature using PubMed as a search engine on Medline. RESULTS: The stages followed by the meninges along the phylogenesis could not be easily compared with their development in vertebrates for methodological aspects and convergence processes throughout evolution. The distinction between arachnoid and pia mater appeared controversial. Several points of descriptive anatomy remain debatable: the functional organization of the arterial network, and the venous and lymphatic drainages, considered differently by classical anatomic and neuroradiological approaches. Spinal meninges are involved in neurodevelopment and neurorepair producing neural stem cells and morphogens, in cerebrospinal fluid dynamics and neuraxis functioning by the synthesis of active molecules, and the elimination of waste products of central nervous system metabolism. CONCLUSION: The spinal meninges should be considered as dynamic functional formations evolving over a lifetime, with ultrastructural features and functional interactions with the neuraxis remaining not fully understood.