A New Surgical Paradigm for Postnatal Repair of Open Neural Tube Defects Using Intraoperative Neurophysiology Monitoring.

An open neural tube defect (ONTD) features an exposed, unclosed neural plate in the form of an expanded and frequently hefty neural placode. Traditional philosophy of ONTD repair aims at preserving the placode at any cost, which often means stuffing the entire thick and unwieldy but non-functional tissue into a tight dural sac, increasing the likelihood of future tethering of the spinal cord. The same philosophy of attempting to save the whole perimetry of the placode also sometimes leads to inadvertent inclusion of parts of the squamous epithelial membrane surrounding the placode into the reconstructed product, only to form inclusion dermoid cyst causing further injury to the neural tissues. Lastly, unsuccessful neurulation of the caudal primary neural tube almost always adversely affects junctional and secondary neurulation resulting in a defective conus, often with a locally active sacral micturition centre that is isolated from and therefore lacking suprasegmental inhibitory moderation. This frequently leads to the development of a spastic, hyperactive, low-compliance and high-pressure bladder predisposing to upstream kidney damage, without benefits of normal bladder function. We are introducing a new surgical technique designed to minimise or eliminate these three undesirable complications of conventional ONTD closure.

Junctional Neural Tube Defect (JNTD): A Rare and Relatively New Spinal Dysraphic Malformation.

Junctional neurulation completes the sequential embryological processes of primary and secondary neurulation as the intermediary step linking the end of primary neurulation and the beginning of secondary neurulation. Its exact molecular process is a matter of ongoing scientific debate. Abnormality of junctional neurulation-junctional neural tube defect (JNTD)-was first described in 2017 based on a series of three patients who displayed a well-formed secondary neural tube, the conus, that is physically separated by a fair distance from its companion primary neural tube and functionally disconnected from rostral corticospinal control. Several other cases conforming to this bizarre neural tube arrangement have since appeared in the literature, reinforcing the validity of this entity. The clinical, neuroimaging, and electrophysiological features of JNTD, as well as the hypothesis of its embryogenetic mechanism, will be described in this chapter.

Intracranial infantile hemangioma - rare entity and common pitfalls: A comprehensive multidisciplinary approach from Neurosurgery, Neurooncology and Neuropathology.

OBJECTIVE: To review the rare entity of pediatric intracranial hemangiomas and discuss surgical pitfalls and pathophysiology in regard to cerebral edema formation. MATERIALS AND METHODS: We describe an extremely rare case of intracranial infantile hemangioma in a neonate with massive cerebral edema, surgically resected urgently because of acute herniation. We review the literature of 46 other pediatric cases of intracranial hemangioma, including congenital capillary hemangiomas. We analyze the data on age, sex distribution, tumor location, growth pattern, edema formation, histopathology, treatment, and outcome. RESULTS: Isolated intracranial infantile hemangiomas in the neonatal period are extremely rare. Some but not all hemangiomas can be treated pharmacologically. Extensive cerebral edema is a frequent finding and can become an enormous problem at surgical resection. The pathogenesis of the edema formation in hemangiomas is complex and is yet not well understood. CONCLUSION: Surgical resection of intracranial hemangiomas is associated with a high morbidity, and pharmacological treatment should, if possible, always be considered first, at least for preoperative optimization. The severity of cerebral edema varies among intracranial hemangiomas, which may be an indicator of different molecular properties of the individual lesions. This implies that further sub-classification of intracranial hemangiomas may be necessary.

New surgical paradigm for open neural tube defects.

INTRODUCTION: An open neural tube defect (ONTD) features an exposed, unclosed neural plate in the form of an expanded, flat, and frequently hefty neural placode. Traditional philosophy of ONTD repair aims at preserving function at any cost, which often means stuffing the entire thick and unwieldy but non-functional placode into a tight dural sac, increasing the likelihood of future tethering of the spinal cord. The same philosophy of attempting to save the whole perimetry of the placode also sometimes leads to inadvertent inclusion of parts of the squamous epithelial membrane surrounding the placode into the reconstructed product, only to form inclusion dermoid cyst causing further injury to the neural tissues. Lastly, defective closure of the caudal primary neural tube usually results in abolition of secondary and junctional neurulation, leaving a defective conus and sacral nerve roots, clinically presenting in most cases with neurogenic bladder and bowel dysfunction. Preserving this trapped but locally active sacral micturition center, isolated from suprasegmental inhibitory moderation, leads to a spastic, hyperactive, low compliance, and high-pressure bladder predisposing to upstream kidney damage, without benefits of normal bladder function. METHOD AND MATERIAL: We report the post-natal surgical treatment of 8 newborn infants with ONTD, in which we resected the non-functional portion of the neural placode identified as such by direct spinal cord/placode and nerve root stimulation, as well as by transcortical evoked motor responses to check for suprasegmental corticospinal connectivity. Any part of the placode without local function or upstream connections was resected, and the small caudal spinal cord stump closed with pia-to-pia microsutures. The patients were followed for pre- and post-operative neuro-urological status and with serial magnetic resonance imaging (MRI) at 3 weeks, 6 months, and 2 years post-repair. Follow-up period ranged from birth to 3 years (mean of 24 months). RESULTS: Of the 8 patients analyzed, 7 had a terminal and one a segmental ONTD. Pre-operative neurological level ranged from L4 to S2. Applying our new surgical paradigm, we found no neurological worsening post-operatively. All patients had a neurogenic bladder and bowel dysfunction but none had a high-pressure bladder on urodynamics studies. Early and late MRIs all showed a loose and capacious neural placode to dural sac relationship. None had an inclusion dermoid cyst. CONCLUSION: We propose a new paradigm for the surgical repair of open neural tube defects with intraoperative neuromonitoring and introduce a safe and reliable technique of placode debulking.

Delayed Contralateral Trigeminal Neuralgia After Microvascular Decompression and Postoperative Changes in Venous Outflow.

A 66-year-old woman had presented with a 3-month history of left trigeminal neuralgia. She had undergone successful microvascular decompression for right-sided trigeminal neuralgia 8 years previously. To optimize visualization, microvascular decompression for trigeminal neuralgia has been commonly associated with sacrifice of the superior petrosal vein during surgery. The absence of sufficient collaterals can result in most of the posterior fossa venous drainage relying solely on the contralateral superior petrosal vein, leading to subsequent vessel enlargement and a compressive effect on the trigeminal nerve and causing iatrogenic contralateral trigeminal neuralgia. We have provided preoperative and intraoperative images illustrating nicely the adapted postoperative change in venous outflow causing contralateral compression of the trigeminal nerve. Consecutive treatment effects should be carefully considered when offering and performing surgical microvascular decompression.

Junctional Neural Tube Defect.

Junctional neurulation represents the most recent adjunct to the well-known sequential embryological processes of primary and secondary neurulation. While its exact molecular processes, occurring at the end of primary and the beginning of secondary neurulation, are still being actively investigated, its pathological counterpart -junctional neural tube defect (JNTD)- had been described in 2017 based on three patients whose well-formed secondary neural tube, the conus, is widely separated from its corresponding primary neural tube and functionally disconnected from corticospinal control from above. Several other cases conforming to this bizarre neural tube arrangement have since appeared in the literature, reinforcing the validity of this entity. The cardinal clinical, neuroimaging, and electrophysiological features of JNTD, and the hypothesis of its embryogenetic mechanism, form part of this review.

The Pantheon Variant of the Classic Cathedral Dome Procedure for Parieto-Occipital Skull Deformities.

OBJECTIVE: To describe a new technique for the reconstruction of parieto-occipital skull deformities. METHODS AND RESULTS: The technique is a variant of the previously described "cathedral dome procedure" used for frontal skull deformities. The authors apply the same principle of remodeling by making meridional slat craniotomies surrounding the depressed dome of the posterior skull deformity, followed by "green-stick fracture-reshaping" of the meridional slats to elevate and support the excised depressed dome. The authors present an illustrative patient with a follow-up of 2 years and an excellent cosmetic result. CONCLUSION: The authors introduce a new operative technique for the reconstruction of parieto-occipital skull deformities with excellent long-term results. The freshly reconstructed occiput resembles the dome of the pantheon in Rome, Italy, whose unique features inspired us to name this procedure the "Pantheon" variant of the cathedral dome operation.

Traumatic Posterior Fossa Subdural Hygroma and Secondary Occlusive Hydrocephalus.

BACKGROUND: Infratentorial subdural hygromas causing secondary occlusive hydrocephalus are extremely rare in children. Only a handful of cases have been reported in the literature. METHODS: We present a case of a 6-month-old infant with an occipital fracture and slow enlargement of a posterior fossa subdural hygroma that culminated in obstructive hydrocephalus. We give a review of the literature on post-traumatic posterior fossa hygroma with secondary occlusive hydrocephalus and discuss its pathogenesis and the mechanism of its later resolution, as well as the available treatment options. RESULTS: A temporary external ventricular drain led to acute relief of the hydrocephalus and subsequent complete resolution of the subdural hygroma. CONCLUSION: Temporary external ventricular drain placement led to complete resolution of the subdural hygroma and hydrocephalus. We recommend close clinical follow-up, and imaging if indicated, for as long as 4 weeks after trauma with occipital skull fractures.

Limited dorsal myeloschisis associated with dermoid elements.

INTRODUCTION: Limited dorsal myeloschisis (LDM) originates from undisjointed neural and cutaneous ectoderms during primary neurulation. Its hallmark is a fibroneural stalk causing tethering on the dorsal spinal cord rostral to the conus. Its treatment is a relatively straightforward resection of the LDM stalk from the spinal cord. METHODS AND RESULTS: On reviewing our series of 75 cases of LDMs, we found that the majority of LDM stalks have only a glioneuronal core within a fibrous stroma, but a small number have been found to have elements of dermoid cyst or a complete dermal sinus tract either contiguous with the fibroneural stalk or incorporated within its glial matrix, not surprising considering the original continuum of cutaneous and neural ectoderm in LDMs' embryogenesis. The dermoid element can be microscopic and escape casual observation, but could grow to large intradural dermoid cysts if part of the dermoid invested LDM stalk is left inside the dura. CONCLUSIONS: We present our series of LDMs associated with dermoid elements and recommend excising the entire length of the intradural LDM stalk from its dural entry point to its merge point with the spinal cord during the initial treatment to avoid secondary deterioration and additional surgery.

Unjoined primary and secondary neural tubes: junctional neural tube defect, a new form of spinal dysraphism caused by disturbance of junctional neurulation.

INTRODUCTION: Primary and secondary neurulation are the two known processes that form the central neuraxis of vertebrates. Human phenotypes of neural tube defects (NTDs) mostly fall into two corresponding categories consistent with the two types of developmental sequence: primary NTD features an open skin defect, an exposed, unclosed neural plate (hence an open neural tube defect, or ONTD), and an unformed or poorly formed secondary neural tube, and secondary NTD with no skin abnormality (hence a closed NTD) and a malformed conus caudal to a well-developed primary neural tube. METHODS AND RESULTS: We encountered three cases of a previously unrecorded form of spinal dysraphism in which the primary and secondary neural tubes are individually formed but are physically separated far apart and functionally disconnected from each other. One patient was operated on, in whom both the lumbosacral spinal cord from primary neurulation and the conus from secondary neurulation are each anatomically complete and endowed with functioning segmental motor roots tested by intraoperative triggered electromyography and direct spinal cord stimulation. The remarkable feature is that the two neural tubes are unjoined except by a functionally inert, probably non-neural band. CONCLUSION: The developmental error of this peculiar malformation probably occurs during the critical transition between the end of primary and the beginning of secondary neurulation, in a stage aptly called junctional neurulation. We describe the current knowledge concerning junctional neurulation and speculate on the embryogenesis of this new class of spinal dysraphism, which we call junctional neural tube defect.

Confounding factors in diagnostics of MGMT promoter methylation status in glioblastomas in stereotactic biopsies.

BACKGROUND: In nonresectable glioblastoma (GBM), stereotactic biopsies are performed to retrieve tissue for diagnostic purposes. The analysis of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation adds prognostic and predictive information. OBJECTIVES: The aim of the study was to detect confounding factors that limit the number of conclusive MGMT promoter methylation results. METHODS: We analyzed 71 consecutive GBM patients undergoing stereotactic biopsy on whom MGMT analysis was performed by methylation-specific polymerase chain reaction. Specimens were correlated to imaging by coregistration and prospective documentation of biopsy localization. Our findings were validated in an additional 62 GBM stereotactic biopsies. RESULTS: Our results demonstrate that the best MGMT promoter methylation results were obtained from samples (n = 71) taken in a tangential manner from tumor areas showing contrast enhancement in magnetic resonance imaging. In the additional validation series of 62 stereotactically biopsied GBM, we were able to increase the rate of conclusive MGMT promoter methylation results from 76.1 to 85.48% by strictly planning the route of biopsy in a tangential manner if possible. CONCLUSIONS: These results underline that within the contrast-enhanced tumor part, choosing the trajectory in a tangential manner increases the diagnostic yield for conclusive MGMT promoter methylation analyses in stereotactic biopsies as a basis for patient stratification and individualized therapy.

Intraoperative bleeding in stereotactic biopsies and its implication on postoperative management: can we predict CT findings?

BACKGROUND: Stereotactic biopsies are procedures with a high diagnostic yield and a low but serious risk of hemorrhage. Postoperative management remains controversial. OBJECTIVES: To evaluate the predictive value of intraoperative bleeding and its implication on postoperative management. METHODS: Cases of intraoperative bleeding were prospectively documented in a consecutive series comprising 303 patients. Categories were as follows: no bleeding, single drop, ≤10 drops and >10 drops. Incidence, size of hemorrhage and neurological deterioration were noted. Hemorrhage on routine postoperative CT scans was correlated with intraoperative findings, sample size, location and pathology. RESULTS: A total of 93 patients (30.7%) showed intraoperative bleeding and 68 (22.4%) showed blood on postoperative CT. In 13 patients (4.3%) the diameter was >1 cm; 19 patients (6.3%) experienced neurological worsening, 9 (3.0%) having postoperative hemorrhage and 3 (1.0%) permanent neurological deficits. Bleeding was associated with postoperative hemorrhage (p < 0.0001). The negative predictive values to rule out any postoperative hemorrhage or hemorrhages >1 cm were 92 and 100%, respectively. Number of samples, location and pathology had no significant influence on postoperative hemorrhage. CONCLUSION: Stereotactic biopsies have a low risk of symptomatic hemorrhages. Intraoperative bleeding is a surveillance parameter of hemorrhage on CT. Therefore, routine postoperative CT may be restricted to patients who show intraoperative bleeding.

Accuracy of 3D fluoroscopy in cranial stereotactic surgery: a comparative study in phantoms and patients.

BACKGROUND: To assess the precision and accuracy of 3D fluoroscopy (XT) in phantoms and patients compared to computed tomography (CT) in localizing stereotactic probes. METHODS: Approval was obtained from the institutional research ethics board. The prospective phantom study was compared to a retrospective patient cohort. Accuracy was assessed by the mean error and precision by the mean dispersion between XT and CT with a cubic or a skull phantom containing metallic spheres installed on plates or along trajectories. Significance was assessed by Friedman's and Levene's test. Secondary endpoints were Euclidean error, other influences e.g. installed frame and radiation exposure. RESULTS: A total of 3,342 distances were assessed in 17 XT and 13 CT phantom scans. The cubic phantom showed mean distance errors of 0.33 mm (SD + -0.46 mm) for XT compared to 0.19 mm (SD + -0.83 mm) for CT scans (p = 0.0004) and a dispersion of 0.22 mm (XT) and 0.70 mm (CT). The dispersion was 0.36 mm with and 0.63 mm without a stereotactic frame (p < 0.0001). The mean Euclidean error was 0.72 mm (SD + -0.59 mm) in the skull phantom and 1.34 mm (SD + -0.82 mm) in the patient cohort. The effective dose was 0.65 mSv for the XT and 1.12 mSv for the CT. CONCLUSIONS: The accuracy of XT imaging in phantoms revealed a slightly lower accuracy but higher precision than the CT. The overall accuracy of XT was higher than that of the stereotactic frame allowing stereotactic localization with about half of the effective dose of a CT-scan.

Correlation of active contact positions with the electrophysiological and anatomical subdivisions of the subthalamic nucleus in deep brain stimulation.

BACKGROUND: The most effective contacts in subthalamic nucleus (STN) deep brain stimulation are reported to be dorsolateral, and suppression of synchronized oscillatory activity might be a mechanism of action. OBJECTIVES: To analyze the optimal contact position in regard to the anatomical and electrophysiological position and to determine whether oscillatory and bursty activity is more frequent around the active contact. METHODS: In 21 patients, the clinically most effective contacts were analyzed according to their relative position to the anatomical and electrophysiological STN center, which was assessed by T2-weighted MRI and microrecording. In 12 out of 21 consecutive patients, autocorrelograms of the action potentials within the vicinity of the active contact were compared to the most ventromedial reference contact. RESULTS: The isocenter of the anatomical and electrophysiological STN had a mean deviation of 0.8 mm (SD 1.45). Thirty-two out of 42 active contacts were found dorsal to the anatomical isocenter of the STN. None of the active contacts were ventral to the STN. Synchronized oscillatory or bursty activity was found in 67% of the patients within the vicinity of the active contact. In 64% of the patients, the ventromedial reference contact showed irregular activity. CONCLUSIONS: Synchronized activity in the autocorrelogram correlates with the most effective contact. The optimal localization of the finally stimulated contact is dorsal to the STN isocenter.

Efficacy and safety of local versus general anesthesia in stereotactic biopsies: a matched-pairs cohort study.

BACKGROUND: Frame-based stereotactic biopsies remain the gold standard for the diagnosis of intracerebral lesions. A major advantage is the ability to perform these procedures under local anesthesia (LA). However, there is no consensus on whether or when to use LA or general anesthesia (GA). It has been postulated that the use of LA may reduce the risk of complications. This study aims to objectify the efficacy and safety of stereotactic biopsies under LA versus GA by analyzing a prospective registry for stereotactic biopsies. METHODS: A prospective registry for stereotactic procedures was analyzed for the activities performed between May 2009 and August 2011. Inclusion criteria were patients undergoing a stereotactic biopsy. Patients with functional stereotactic procedures, cyst or abscess evacuation, and children were excluded. Of the remaining 274 patients, 204 could be randomly matched considering sex, age, American Society of Anesthesiologists (ASA) classification, and type of hospitalization. The primary endpoint was the diagnostic yield. Secondary endpoints were safety and procedural time intervals. RESULTS: Ninety-six percent of diagnosis was achieved in the LA group and 94% within the GA group. There was no significant difference in the overall complication rate. However, the rate of pulmonary complications was higher in the GA group (P=0.059). The rate of bleeding was significantly higher in the LA group (P=0.003) intraoperatively. However, no significant difference was found clinically or on routine postoperative computed tomography scan reports. There was a significant reduction in the time spent in the operating room within the LA group (P<0.001). CONCLUSIONS: The type of anesthesia may not interfere with the diagnostic yield in stereotactic biopsies. Patients operated under LA are less likely to suffer pulmonary complications. Furthermore, LA could spare hospital resources in this setting.

Structural biology of mammalian lipoxygenases: enzymatic consequences of targeted alterations of the protein structure.

Lipoxygenases form a heterogeneous family of lipid peroxidizing enzymes, which have been implicated in the pathogenesis of diseases with major health political relevance (bronchial asthma, atherosclerosis, cancer, and osteoporosis). The crystal structures of one mammalian lipoxygenase and of two plant isoenzymes have been solved and the structural bases of important enzyme properties (reaction specificity, membrane binding, and suicidal inactivation) have been investigated in the past. This review will briefly summarize our current understanding on the structural biology of the most important mammalian lipoxygenase isoforms and will also address selected mechanistic features of the lipoxygenase reaction.