Comparative analysis of linezolid, vancomycin, and hyperbaric oxygen therapies in a rat model of ventriculoperitoneal shunt infection.

PURPOSE: Staphylococcus epidermidis is the most common causative microorganism of ventriculoperitoneal shunt infections. This study aimed to compare linezolid and vancomycin treatments and to examine the effect of these antibiotics alone and combined with hyperbaric oxygen therapy on the amount of bacterial colonies in the experimental S. epidermidis shunt infection model. METHODS: A shunt catheter was placed in the cisterna magna of 49 adult male Wistar albino rats. The rats were randomly divided into seven groups, as follows: sterile control, infected control, vancomycin, linezolid, hyperbaric oxygen, vancomycin + hyperbaric oxygen, linezolid + hyperbaric oxygen. In all groups except the sterile control group, 0.2 ml 107 CFU/mL S. epidermidis was inoculated to the cisterna magna. Parenteral vancomycin was administered 40 mg/kg/day to the vancomycin groups, and 50 mg/kg/day of enteral linezolid to the linezolid groups. Hyperbaric oxygen groups were given 100% oxygen at a pressure of 2.4 ATA for 50 min a day. One day after the last treatment, colony quantities in the shunt catheters and CSF were analyzed. RESULTS: The number of CSF colonies in the linezolid group was significantly lower than in the vancomycin group (p < 0.05). The number of CSF colonies in the linezolid + HBO group was significantly lower than in the vancomycin + HBO group (p < 0.05). CONCLUSIONS: Linezolid treatment was found to be more effective than vancomycin in ventriculoperitoneal shunt infection caused by S. epidermidis. There was no statistical difference among other treatment groups. Hyperbaric oxygen therapy is shown to contribute to the sterilization of cultures.

Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas.

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway  in neoplasia.

Pentoxifylline and Vitamin E Can Restrict Radiation Necrosis via Vascular Pathways, Experimental Study in an Animal Model.

OBJECTIVE: Radiation necrosis (RN) is a long-term side effect of Gamma Knife stereotactic radiosurgery that may require surgical intervention. Pentoxifylline and vitamin E have previously been shown to be effective in the treatment of RN in the published literature, but there are no data on the prophylactic use of these molecules or, more importantly, whether prophylaxis is required. METHODS: The iatrogenic RN model included 50 Sprague-Dawley rats of both sexes. There were 7 treatment subgroups established. Gamma-Plan 8.32 was used to plan after magnetic resonance scans were performed in a specially designed frame. The injection doses used in the treatment groups were vitamin E (30 mg/kg/day in a single dose) and pentoxifylline (50 mg/kg/day in 2 doses). Control magnetic resonance scans were performed at the end of a 16-week treatment, and the subjects were decapitated for pathological evaluations. RESULTS: The intensity of hypoxia - inducible factor 1α immunoreactivity is statistically significantly lower in the therapeutic vitamin E, prophylactic pentoxifylline and vitamin E, and therapeutic pentoxifylline and vitamin E groups than in the other groups. Similarly, the intensity of vascular endothelial growth factor immunoreactivity was reduced in the therapeutic vitamin E and prophylactic pentoxifylline and vitamin E treatment modality groups. When compared with other groups, the therapeutic pentoxifylline group had significantly fewer vascular endothelial growth factor-immunoreactive cells in the perinecrotic area, with an accompanying decreased contrast enhancement pattern. CONCLUSIONS: Both vitamin E and pentoxifylline are effective for the treatment and/or restriction of RN, either alone or in combination. The use of these molecules as a preventive measure did not outperform the therapeutic treatment.

Safety and efficacy of flow diverter stents in the treatment of middle cerebral artery aneurysms: a single-center experience and follow-up data

PURPOSE: This study aims to evaluate the safety and efficacy of flow diverters (FDs) in the treatment of middle cerebral artery (MCA) aneurysms and share the follow-up (F/U) results. METHODS: The treatment and F/U results of 76 MCA aneurysms treated with the flow re-direction endoluminal device (FRED), FRED Jr., and pipeline embolization device (PED) FD stents were evaluated retrospectively. The aneurysm occlusion rates were compared between FDs, and the integrated and jailed branches were evaluated through follow-ups. The oversizing of the stent was compared between occluded/non-occluded aneurysms and integrated branches. RESULTS: The mean F/U duration was 32 ± 6.3 months, and the mean aneurysm diameter was 4.45 mm. A total of 61 (80.3%) aneurysms were wide-necked; 73 (96.1%) were saccular; 52 (68.4%) were located at the M1 segment; and 36 (45.6%) FREDs, 23 (29.1%) FRED Jr.s, and 19 (24.1%) PEDs were used for treatment. The overall occlusion rates for the 6-, 12-, 24-, 36-, and 60-month digital subtraction angiographies were 43.8%, 63.5%, 73.3%, 85.7%, and 87.5% respectively. The last F/U occlusion rates were 67.6% for FRED, 66.7% for PED, and 60.6% for FRED Jr. (P = 0.863). An integrated branch was covered with an FD during the treatment of 63 (82.8%) aneurysms. A total of six (10%) of the integrated branches were occluded without any symptoms at the last F/U appointment. The median oversizing was 0.45 (0-1.30) for occluded aneurysms, and 0.50 (0-1.40) for non-occluded aneurysms (P = 0.323). The median oversizing was 0.70 (0.45-1.10) in occluded integrated branches and 0.50 (0-1.40) in non-occluded branches (P = 0.131). In-stent stenosis was seen in 22 (30.1%) of the stents at the 6-month F/U and in only 2 (4.7%) at the 24-month F/U. Thus, none of the patients had any neurological deficits because of the in-stent stenosis. Severe in-stent stenosis was seen in two stents. CONCLUSION: MCA aneurysms tend to be complex, with integrated branches and potentially wide necks. FD stents are safe and effective in the treatment of MCA aneurysms, and the patency of the side and jailed branches is preserved in most cases. Higher occlusion and lower in-stent stenosis rates are seen with longer F/U durations.

A new method for quantification of frontal retrusion and complex skull shape in metopic craniosynostosis: a pilot study of a new outcome measure for endoscopic strip craniectomy.

OBJECTIVE: The objective of this study was to propose a new skull outline-based method to objectively quantify complex 3D skull shapes and frontal and supraorbital retrusion in metopic craniosynostosis using 3D photogrammetry. METHODS: A standard section from 3D photogrammetry, which represents the trigonocephalic shape, was used in this study. From the midpoint of the area of this section, half diagonals were calculated to the skull outline at 5° increments in the anterior half of the head. These half diagonals were used to create a sinusoidal curve, and the area under the sinusoidal curve (AUC) was used to represent the mathematical expression of the trigonocephalic head shape. The AUC from 0° to 180° (90° from the midline to each side) was calculated and is referred to as AUC0→180. The AUC from 60° to 120° (30° from the midline to each side) was also calculated and is referred to as AUC60→120. A total of 24 patients who underwent endoscopic strip craniectomy and 13 age- and sex-matched controls were included in the study. The AUC values obtained in patients at different time points and controls were analyzed. RESULTS: The mean preoperative AUC60→120 and AUC0→180 in the patients were significantly lower than those in control individuals. The increase in both AUC60→120 and AUC0→180 values is statistically significant at the discontinuation of helmet therapy and at final follow-up. Receiver operating characteristic curve analysis indicated that AUC60→120 is a more accurate classifier than AUC0→180. CONCLUSIONS: The proposed method objectively quantifies complex head shape and frontal retrusion in patients with metopic craniosynostosis and provides a quantitative measure for follow-up after surgical treatment. It avoids ionizing radiation exposure.

Modified endoscopic strip craniectomy technique for sagittal craniosynostosis: provides comparable results and avoids bony defects.

PURPOSE: This study describes a modified technique addressing bony defects and incomplete ossification after endoscopic strip craniectomy (ESC) for SC followed by postoperative helmet therapy (PHT). The study aims to delineate quantitative and qualitative outcomes of this modified ESC technique followed by PHT and discern the optimal duration of PHT following ESC. A secondary aim is to address the effects of the technique on bony defects. METHODS: Patients undergoing ESC followed by PHT between 2017 and 2021 were included. Patient sex, age at surgery, duration of surgery, red blood cell transfusion, length of hospital stay, PHT duration, cephalic index (CI) at multiple time points, and bony defect information were collected. Descriptive and correlative analysis was done. RESULTS: Thirty-one patients (25 male, 6 female) were operated in study period. Mean age at surgery was 12.81 weeks, mean duration of surgery was 57.50 min, average transfused RBC volume was 32 cc, mean length of hospital stay was 1.84 days, mean PHT duration was 33.16 weeks, and mean follow-up time was 63.42 weeks. Mean preoperative CI was 70.6, and mean CI at the end of PHT was significantly higher, being 77.1. Maximum improvement in CI (CImax) took place at week 22.97. PHT duration did not have a correlation with CI at last follow up. There were no bony defects. CONCLUSION: Modified ESC technique is effective in successful correction of sagittal craniosynostosis. CImax already takes place, while PHT is continuing, but there is no certain time point for dishelmeting. The technique avoided bony defects and incomplete ossification.

Long-term results and comparison of flow re-direction endoluminal device and pipeline embolization device in endovascular treatment of intracranial carotid aneurysms.

OBJECTIVE: This study aims to compare the efficacy, safety, and long-term outcomes of two flow diverters, i.e., pipeline embolization device and flow re-direction endoluminal device, in the treatment of distal carotid aneurysms. METHODS: A total of 138 patients with 175 aneurysms were included from February 2012 to September 2019. Ninety-nine aneurysms were treated with flow re-direction endoluminal device and 76 with pipeline embolization device. Angiographic follow-ups were at the 6th, 12th, 24th, 36th, and 60th months; the O'Kelly-Marotta grading scale was used to assess aneurysms occlusion. Outcomes of two devices were compared; possible associations regarding patient characteristics, aneurysm properties, treatment details, and adverse events were evaluated. RESULTS: The mean follow-up period was 33 months, with 10 patients lost to follow-up. Occlusion rates at the 6th and 12th months and during the last follow-up were similar for flow re-direction endoluminal device (81%, 84%, and 90%) and pipeline embolization device (82%, 85%, and 93%). Occlusion rates were also similar after stand-alone use without coiling. There was no significant difference regarding adverse event rates with a 10.9% overall complication rate, 3.6% mortality, and 0.7% permanent morbidity. All the mortality and morbidity were related to hemorrhagic complications. Device deployment failure was observed with five flow re-direction endoluminal devices and two pipeline embolization devices, whereas two severe in-stent stenoses occurred with each device. CONCLUSIONS: Both flow re-direction endoluminal device and pipeline embolization device are feasible and effective in flow diversion of distal internal carotid artery aneurysms, with similar adverse events rates and aneurysm occlusion success. Aneurysm occlusion rates increase with time, while the presence of an integrated branch significantly decreases treatment success.

Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience.

PURPOSE: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. METHODS: Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. RESULTS: At the time of diagnosis, the median age was 48 (17-77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1-68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). CONCLUSION: Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.

Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus.

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.

Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

OBJECTIVE: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts. METHODS: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features. RESULTS: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation. CONCLUSIONS: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

Anterior third ventricular height and infundibulochiasmatic angle: two novel measurements to predict clinical success of endoscopic third ventriculostomy in the early postoperative period.

OBJECTIVE: The authors sought to develop a set of parameters that reliably predict the clinical success of endoscopic third ventriculostomy (ETV) when assessed before and after the operation, and to establish a plan for MRI follow-up after this procedure. METHODS: This retrospective study involved 77 patients who had undergone 78 ETV procedures for obstructive hydrocephalus between 2010 and 2015. Constructive interference in steady-state (CISS) MRI evaluations before and after ETV were reviewed, and 4 parameters were measured. Two well-known standard parameters, fronto-occipital horn ratio (FOHR) and third ventricular index (TVI), and 2 newly defined parameters, infundibulochiasmatic (IC) angle and anterior third ventricular height (TVH), were measured in this study. Associations between preoperative measurements of and postoperative changes in the 4 variables and the clinical success of ETV were analyzed. RESULTS: Of the 78 ETV procedures, 70 (89.7%) were successful and 8 (10.3%) failed. On the preoperative MR images, the mean IC angle and anterior TVH were significantly larger in the successful procedures. On the 24-hour postoperative MR images of the successful procedures, the mean IC angle declined significantly from 114.2° to 94.6° (p < 0.05) and the mean anterior TVH declined significantly from 15 to 11.2 mm (p < 0.05). The mean percentage reduction of the IC angle was 17.1%, and that of the anterior TVH was 25.5% (both p < 0.05). On the 1-month MR images of the successful procedures, the mean IC angle declined significantly from 94.6° to 84.2° (p < 0.05) and the mean anterior TVH declined significantly from 11.2 to 9.3 mm (p < 0.05). The mean percentage reductions in IC angle (11%) and anterior TVH (16.9%) remained significant at this time point but were smaller than those observed at 24 hours. The 6-month and 1-year postoperative MR images of the successful group showed no significant changes in mean IC angle or mean anterior TVH. Regarding the unsuccessful procedures, there were no significant changes observed in IC angle or anterior TVH at any of the time points studied. Reduction of IC angle and reduction of anterior TVH on 24-hour postoperative MR images were significantly associated with successful ETV. However, no clinically significant association was found between FOHR, TVI, and ETV success. CONCLUSIONS: Assessing the IC angle and anterior TVH on preoperative and 24-hour postoperative MR images is useful for predicting the clinical success of ETV. These 2 measurements could also be valuable as radiological follow-up parameters.

In Vitro Effects of Mesenchymal Stem Cells and Various Agents on Apoptosis of Glioblastoma Cells.

AIM: To investigate a new anti-tumor treatment method using stem cells transfected with specific genes and proteins that induce apoptosis in tumor cells. MATERIAL AND METHODS: We used glioblastoma (GBM) cells and human adipose tissue-derived mesenchymal stem cells (ADMSCs) in this study. The AD-MSCs were transfected with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To overcome apoptosis resistance in tumor cells, we used suberoylanilide hydroxamic acid (SAHA) as the histone deacetylase inhibitor and embelin as the X-linked inhibitor of apoptosis protein (XIAP). In addition, we silenced the XIAP gene on GBM cells with the shXIAP plasmid. Following the determination of half-maximal effective concentration (EC50%) doses of SAHA and embelin, GBM cells were incubated with them for 24 hours. XIAP-silenced and XIAP-non-silenced GBM cells were cultured with TRAIL-nontransfected and TRAIL-transfected stem cells for 24 hours. Viability and cell cycle analysis of all groups were determined using annexin V/propidium iodide and cell cycle method via flow cytometry. RESULTS: TRAIL-transfected AD-MSCs, XIAP silencing, embelin, and SAHA induced apoptosis in GBM cells and decreased their proliferation, whereas TRAIL-non-tranfected AD-MSCs did not. CONCLUSION: Engineered stem cell therapies and molecular studies show promise in developing combination therapies for effective treatment of GBM.

De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus.

Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 × 10-7), SMARCC1 (p = 8.15 × 10-10), and PTCH1 (p = 1.06 × 10-6). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 × 10-4). Together, these probands account for ∼10% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications.

Acute Obstructive Hydrocephalus due to a Giant Posterior Cerebral Artery Aneurysm in a Pediatric Patient.

INTRODUCTION: Intracranial aneurysms are very rare in children. Although subarachnoidal hemorrhage (SAH) is by far the most common presentation of aneurysms in the majority of the pediatric case series, it is not rare for an unruptured aneurysm to present with a mass effect. Acute hydrocephalus is a common finding following aneurysmal SAH. However, this malady may develop even in the absence of SAH but secondary to direct obstruction by a giant aneurysm. This situation is extremely rare in children, with only a few known case reports in the literature. CASE REPORT: We report the case of a 10-year-old girl who presented with signs and symptoms of acute hydrocephalus; further radiological evaluation revealed obstructive hydrocephalus and a giant posterior cerebral artery aneurysm. Following endovascular treatment of the aneurysm, hydrocephalus was completely resolved, and the patient was symptom free. CONCLUSION: Although they are very rare, giant intracranial aneurysms must be kept in mind during the differential diagnosis of pediatric acute hydrocephalus cases. Hydrocephalus may resolve spontaneously after the successful treatment of these aneurysms.

Somatosensory evoked potentials as a screening tool for diagnosis of spinal pathologies in children with treatment refractory overactive bladder.

PURPOSE: To evaluate the usefulness of somatosensory evoked potential as a screening tool for spinal pathologies in patients with treatment refractory overactive bladder. METHODS: This prospective study was performed between January 2011 and January 2014. Children >5 years old with treatment refractory overactive bladder were enrolled after exclusion of anatomical and neurological causes of incontinence. All patients underwent urodynamic studies, spinal MRI, and somatosensory evoked potential (SEP). Sensitivity, specificity, PPV, and NPV were calculated for SEP. RESULTS: Thirty-one children (average age 8.3 ± 2.9 years) were included in the study. SEP was abnormal in 13 (41.9%), and MRI was abnormal in 8 (25.8%) patients. SEP was found to have a sensitivity of 87.5%, a specificity of 73.9%, positive predictive value of 53.85%, and negative predictive value (NPV) of 94.4%. CONCLUSION: In patients with treatment refractory OAB, SEP is an important tool for the screening of tethered cord/spinal pathologies. Our results suggest that a child with a normal SEP study in this group of patients may not require further investigation with MRI.

Drainage Vein Induced Hydrocephalus Caused by an Unruptured Arteriovenous Malformation in an Adult Presenting with Visual Loss.

Arteriovenous malformations (AVMs) commonly present with seizures and hemorrhage. Hydrocephalus associated with an unruptured AVM in an adult patient is exceedingly rare. A 37-year-old male patient presented with total visual loss in his right eye and severe impairment in his left eye. His evaluation showed an unruptured right frontal AVM and bilaterally dilated lateral ventricles. The major draining vein of the AVM was obstructing the third ventricle. An urgent external ventricular drainage was used as the first line intervention and followed with a ventriculoperitoneal shunt two days later. His definitive treatment for AVM was staged stereotactic gamma-knife radiosurgery. Unruptured AVMs in adult patients may rarely cause hydrocephalus. Visual loss caused by such a hydrocephalus has not been reported before. Both communicating and non-communicating type hydrocephalus can be seen with unruptured AVMs, and have different pathophysiological mechanisms. Our patient was treated with ventriculoperitoneal shunting, and visual examination remained unchanged after the operation. Visual loss caused by hydrocephalus associated with an unruptured AVM in an adult patient has not been reported before. It may indicate an association of different pathophysiological mechanisms. The treatment must depend on the neurological condition of the patient.

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus.

Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

Direct withdrawal of a knife lodged in the thoracic spinal canal in a patient with normal neurologic examination: is it safe?

Stab wound injuries to the spinal cord are rare, although they commonly cause complete or incomplete neurological deficits. Normal neurological examination with a knife traversing the spinal canal is extremely rare. Here we report on a patient with a knife lodged in the thoracic spine with normal neurological examination and describe direct withdrawal of the knife with excellent results that have not been reported to date. A 50-year-old male patient was admitted to the emergency service because of his sustaining a stab wound to thoracic 3-4 level due to a knife traversing the spinal canal and still lodged in the vertebral bodies. His neurological examination was normal. The knife was withdrawn in the operating room under general anesthesia without bleeding or cerebrospinal fluid leakage. After withdrawal neurological examination was normal and control magnetic resonance imaging showed no abnormalities. Surgical exploration is suggested for spinal stab wounds if there is a retained body. Some authors recommend exploration even no foreign body is detected. Incomplete or complete cord injuries deserve surgical exploration, but in a patient with normal neurological examination direct withdrawal can be a safe option. Exploration of the wound surgically may have risks associated with enlarging the incision, muscle dissection, enlarging dural tear and bony removal, which may have long-term adverse effects. The operation team must be ready for urgent exploration. Cerebrospinal fluid leakage, excessive bleeding or any neurological deficit after removal must mandate surgical exploration. Long-term close follow-up of the patient has paramount importance for late complications such as infection and pseudomeningocele development.

Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4 gene.

We report an association between a new causative gene and spastic paraplegia, which is a genetically heterogeneous disorder. Clinical phenotyping of one consanguineous family followed by combined homozygosity mapping and whole-exome sequencing analysis. Three patients from the same family shared common features of progressive complicated spastic paraplegia. They shared a single homozygous stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous mutation (c.853_871del19) in the gene coding the kinesin light chain 4 protein (KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a stop codon and thus a truncated messenger RNA and protein. The association of a KLC4 mutation with spastic paraplegia identifies a new locus for the disease.

Spinal epidural cavernous angioma: two case reports and review of the literature.

Cavernous angiomas are vascular malformations that occur most frequently in the supratentorial area of the central nervous system (CNS). Spinal epidural occurrence is rare. This article describes 2 cases of spinal epidural cavernous angioma. The lesions were hypo- to isointense on T1-weighted magnetic resonance images (MRIs) and hyperintense on T2-weighted images. Both were enhanced homogenously with intravenous contrast. Total resection was achieved in both cases, and the lesions were histopathologically diagnosed as cavernous angiomas. The patients' symptoms regressed postsurgery. Although the MRI features of cavernous angiomas are well known, spinal epidural occurrence is rare and many differential diagnoses have similar clinical and imaging findings. It is important to definitively diagnose these lesions prior to surgery in order to prevent possible intraoperative complications such as massive bleeding and to maximize chances for complete resection. In addition to case descriptions, this article includes a thorough literature review to raise clinical awareness about this well-known but rare spinal entity.