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.

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.

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.

The growth of the foramen magnum in Crouzon syndrome.

BACKGROUND: Though the craniovertebral junction is often abnormal in children with Crouzon's syndrome, no study had measured accurately the size of their foramen magnum (FM). PATIENTS AND METHODS: We compared the FM size (area, diameters) on computed tomography examination in 21 children with a genetically confirmed Crouzon's syndrome prior to any surgery and in 23 control children without craniofacial abnormalities. We extrapolated the growth pattern in both groups. RESULTS: We found a statistically significant smaller FM area (p=0.0228), FM sagittal diameter (p=0.0287), and FM sagittal posterior diameter (p=0.0023) in children with Crouzon's syndrome. No differences were detected with regard to the transversal diameter. Hydrocephalus in children with Crouzon's syndrome was associated with a small FM area (p=0.05), small sagittal diameter (p=0.023), small sagittal posterior diameter (p=0.0173), and reduced transversal diameter (p=0.03985). No association of the aforementioned findings was found with the position of the cerebellar tonsils or the lambdoid suture functional state (open or fused). Comparable results were observed among the two genetic forms (exon 8 or 10 mutations). Concerning the growth pattern, a first phase of rapid increase and a second phase of slow increase could be recognized in all the measurements in both populations, though with some significant differences. DISCUSSION AND CONCLUSIONS: The growth of FM follows a biphasic pattern in both Crouzon's and control children. The sagittal diameter and the global size of the FM are mostly affected in children with Crouzon's syndrome. The small FM, especially its posterior part, is likely to play a key role in the physiopathology of hydrocephalus.