[Long-term prognosis of idiopathic chronic adult hydrocephalus: I. The University Hospital Marqués de Valdecilla diagnostic and therapeutic protocol]. / Pronóstico a largo plazo de la hidrocefalia crónica del adulto idiopática: I. Protocolo diagnóstico-terapéutico del Hospital Universitario Marqués de Valdecilla.

INTRODUCTION: Despite the existence of published guidelines for more than a decade, there is still a substantial variation in the management of idiopathic normal pressure hydrocephalus due to its diagnostic and therapeutic complexity. DEVELOPMENT: The diagnostic and therapeutic protocol for the management of idiopathic normal pressure hydrocephalus in use at the Department of Neurosurgery of the University Hospital Marqués de Valdecilla is presented. The diagnostic process includes neuropsychological testing, phase contrast cine MRI, urodynamic evaluation, continuous intracranial pressure monitoring, cerebrospinal fluid hydrodynamics by means of lumbar infusion testing, and intra-abdominal pressure measurement. A patient is considered a surgical candidate if any of the following criteria is met: mean intracranial pressure >15mmHg, or B-waves present in >10% of overnight recording; pressure-volume index <15ml, or resistance to cerebrospinal fluid outflow (ROUT) >4.5mmHg/ml/min in bolus infusion test; ROUT >12mmHg/ml/min, intracranial pressure >22mmHg, or high amplitude B-waves in the steady-state of the continuous rate infusion test; or a clinical response to high-volume cerebrospinal fluid withdrawal. CONCLUSIONS: The implementation of a diagnostic and therapeutic protocol for idiopathic normal pressure hydrocephalus management could improve various aspects of patient care. It could reduce variability in clinical practice, optimise the use of health resources, and help in identifying scientific uncertainty areas, in order to direct research efforts in a more appropriate way.

Cellular plasticity confers migratory and invasive advantages to a population of glioblastoma-initiating cells that infiltrate peritumoral tissue.

Glioblastoma (GBM) is associated with infiltration of peritumoral (PT) parenchyma by isolated tumor cells that leads to tumor regrowth. Recently, GBM stem-like or initiating cells (GICs) have been identified in the PT area, but whether these GICs have enhanced migratory and invasive capabilities compared with GICs from the tumor mass (TM) is presently unknown. We isolated GICs from the infiltrated PT tissue and the TM of three patients and found that PT cells have an advantage over TM cells in two-dimensional and three-dimensional migration and invasion assays. Interestingly, PT cells display a high plasticity in protrusion formation and cell shape and their migration is insensitive to substrate stiffness, which represent advantages to infiltrate microenvironments of different rigidity. Furthermore, mouse and chicken embryo xenografts revealed that only PT cells showed a dispersed distribution pattern, closely associated to blood vessels. Consistent with cellular plasticity, simultaneous Rac and RhoA activation are required for the enhanced invasive capacity of PT cells. Moreover, Rho GTPase signaling modulators αVß3 and p27 play key roles in GIC invasiveness. Of note, p27 is upregulated in TM cells and inhibits RhoA activity. Gene silencing of p27 increased the invasive capacity of TM GICs. Additionally, ß3 integrin is upregulated in PT cells. Blockade of dimeric integrin αVß3, a Rac activator, reduced the invasive capacity of PT GICs in vitro and abrogated the spreading of PT cells into chicken embryos. Thus, our results describe the invasive features acquired by a unique subpopulation of GICs that infiltrate neighboring tissue.

[Insular-opercular associative tracts: Review of their anatomy and relevance for the trans-opercular approach to the insula]. / Fascículos asociativos ínsulo-operculares: revisión de su anatomía y de las implicaciones para el abordaje transopercular a la ínsula.

INTRODUCTION: The insula is a highly connected area, as an intricate network of afferent and efferent projections connect it with adjacent and distant cortical regions. OBJECTIVE: To perform an extensive review of recent literature to analyse the anatomy of the associative tracts related to the insula. RESULTS: The frontal aslant tract, arcuate fasciculus, horizontal portion of the superior longitudinal fasciculus and the middle longitudinal fasciculus are associative tracts connected to the opercula. The inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus run under the anterior and inferior portion of the insula. CONCLUSIONS: the pars triangularis and orbicularis of the inferior frontal gyrus, as well as the middle and anterior part of the superior temporal gyrus, have few connections with the perisylvian associative network. Consequently, in the trans-opercular approach to the insula, these 2 regions represent anatomical corridors that give access to the insula. The IFOF and the uncinate fasciculus represent the deep functional margin of resection.

Cost-utility of maximal safe resection of WHO grade II gliomas within eloquent areas.

BACKGROUND: Despite the growing use of intraoperative electrical stimulation (IES) mapping for resection of WHO grade II gliomas (GIIG) located within eloquent areas, some authors claim that this is a complex, time-consuming and expensive approach, and not well tolerated by patients, so they rely on other mapping techniques. Here we analyze the health related quality of life, direct and indirect costs of surgeries with and without intraoperative electrical stimulation (IES) mapping for resection of GIIG within eloquent areas. METHODS: A cohort of 11 subjects with GIIG within eloquent areas who had IES while awake (group A) was matched by tumor side and location to a cohort of 11 subjects who had general anesthesia without IES (group B). Direct and indirect costs (measured as loss of labor productivity) and utility (measured in quality adjusted life years, QALYs), were compared between groups. RESULTS: Total mean direct costs per patient were $38,662.70 (range $19,950.70 to $61,626.40) in group A, and $32,116.10 (range $22,764.50 to $46,222.50) in group B (p = 0.279). Total mean indirect costs per patient were $10,640.10 (range $3,010.10 to $86,940.70) in group A, and $48,804.70 (range $3,340.10 to $98,400.60) in group B (p = 0.035). Mean costs per QALY were $12,222.30 (range $3,801.10 to $47,422.90) in group A, and $31,927.10 (range $6,642.90 to $64,196.50) in group B (p = 0.023). CONCLUSIONS: Asleep-awake-asleep craniotomies with IES are associated with an increase in direct costs. However, these initial expenses are ultimately offset by medium and long-term costs averted from a decrease in morbidity and preservation of the patient's professional life. The present study emphasizes the importance to switch to an aggressive and safer surgical strategy in GIIG within eloquent areas.

Complications of endoscopic microdiscectomy using the EASYGO! system: is there any difference with conventional discectomy during the learning-curve period?

BACKGROUND: Microendoscopic discectomy (MED) is emerging as a minimally invasive alternative to conventional microsurgical discectomy (MSD). EASYGO! is a new system for spinal endoscopy that claims smooth transition from MSD to MED, with a reduced learning curve period. The aims of this study were to describe the complications that appeared during the learning curve period of MED and to compare their incidence with the rate and type of complications that occurred during a simultaneous non-randomised series of standard MSDs. METHODS: Between July 2009 and December 2010, 138 patients underwent scheduled first-time discectomy in our institution, 37 using an MED approach and 101 by a conventional MSD. A MED learning curve was obtained by plotting every case with its respective operative time. Complications, length of hospital stay, need of further surgery and outcome were prospectively recorded in both groups. RESULTS: The mean operative time was 66 min for the MSD group and 100 min for the MED group, although for the last 14 cases of the latter group the time was reduced. Curve-fitting techniques showed that the inverse equation, ƒ(x) = 122.12/x + 73.05, had the best correlation between case number and operative time. The learning curve was overcome after the 30th case. Complications occurred in 9.8 % of the MSD group and 8.1 % of the MED group (P = 0.49). Average length of hospital stay was 2.36 days for the MED group and 3.36 days for the MSD group (P = 0.01). The procedure successfully relieved patient symptoms in 68.63 % of the MSD group and 89.92 % of the MED group. No revision surgery was required in the MED group, but it was necessary in ten patients of the MSD group. CONCLUSIONS: Between 25 and 30 cases are needed to reach the learning curve's asymptote of MED. Even during this initial learning period MED is a safe procedure, with comparable results to those obtained with conventional MSD and with a similar complication rate. The key points for reducing intraoperative complications are an adequate expertise in MSD, a precise selection of initial cases, a proper surgical planning and a careful technique, which are mandatory to avoid unnecessary neurological injury in an otherwise secure surgical approach.

[Penetrating spinal injury with glass fragments causing CSF leak: case report]. / Fístula de líquido cefalorraquídeo secundaria a traumatismo medular por cristales: a propósito de un caso.

Penetrating injuries to the spine are important causes of spinal cord traumatism. There are two varieties: gunshot or stab wounds. Within the second category, sharp knifelike objects and, rarely, glass are found. This article presents a case of penetrating glass injury to the lumbar spine in an 18-year-old girl, with the migration of pieces of glass within muscles and spinous process until reaching the dural sac.

[Controversy in the management of WHO grade II gliomas in eloquent brain areas: recent literature review]. / Controversias en el tratamiento de los gliomas OMS grado II localizados en áreas elocuentes: revisión de la bibliografía reciente.

Recent studies have shown that diffuse grade II gliomas (GGII) located in eloquent brain areas represent over 80% of all GGII. The optimal management of these tumours is still controversial. It has long been considered that surgery is not an option for GGII within eloquent areas, due to the high risk of inducing postoperative sequelae in patients with normal neurological explorations. However, the safety of these surgeries has significantly improved in recent years due to the rapid development of techniques enabling a precise mapping of brain functions. Noninvasive functional neuroimaging techniques have been recently developed, enabling cortical mapping of the entire brain prior to surgical procedures. Such precise data provide a preoperative estimation of the location of eloquent areas in relation to the tumour, which is essential for surgical planning and preoperative assessment of morbidity for various surgical approaches. The intraoperative electrical stimulation (IES) mapping technique consists in the application of a bipolar electrode on the brain tissue, enabling an accurate location of brain functions. This provides unique assistance in GGII resection, as it generates a discrete and transient "virtual" lesion within the eloquent tissue. Tumour removal is then tailored according to functional boundaries in order to optimise the quality of resection and to minimise the risk of postoperative sequelae, preserving quality of life. For patients with a GGII in an eloquent area, the possibility of an early resection should be evaluated by a multidisciplinary neuro-oncology team specialising in the management of such tumours.

[WHO grade II gliomas: review of the current management]. / Gliomas hemisféricos OMS grado II: revisión del manejo actual.

The optimal management of diffuse WHO grade II gliomas (GGII) is still controversial. Some authors propose a long-term radiological follow-up of the tumor, others perform a biopsy and treat only if clinical or radiological signs of progression, finally, others propose an active treatment from diagnosis. There is mounting evidence that suggest that expectant management is no longer optimal, supporting active treatment from diagnosis. In the present work, an extensive review of the recent literature was performed, in order to clarify some of these controversies. Neuroimaging techniques, such as magnetic resonance imaging (MRI), multivoxel spectroscopy or methionine positron emission tomography (PET), give valuable information about the tumor, but lack of sufficient reliability to make a definitive diagnosis of GGII. Stereotactic biopsy leads to misdiagnosis in up to 71% of cases, which has been associated with sampling errors and inter-observer variability due to the small sample obtained. Therefore, it is now considered that a definitive diagnosis of GGII requires a detailed histological analysis of the sample after maximum tumor removal. Despite the lack of class I evidence, there is growing evidence from cohort studies, favoring extensive surgical resection to improve survival and time to tumor degeneration. Surgery is also effective to treat epilepsy, as an improvement in up to 76% of drug-resistant epilepsies has been documented. Consequently, surgery is now considered as a crucial step for diagnosis and treatment of these tumors. Early radiotherapy after surgery lengthens the period without progression but does not affect overall survival, and is related to cognitive disorders that affect quality of life. Hence, this treatment could be deferred until tumor progression.

[Establishment of a modified surgical safety checklist for the neurosurgical patient: Initial experience in 400 cases]. / Implantación de la lista de verificación quirúrgica de la Organización Mundial de la Salud modificada para el paciente neuroquirúrgico: experiencia inicial en 400 casos.

INTRODUCTION: Adverse events during diagnostic and therapeutic procedures and medical errors associated with them are an important source of patient morbidity. In an attempt to reduce these, the WHO has proposed a series of measures applicable to medical and surgical patients. Within these last ones is the surgical safety checklist (SSC), a brief questionnaire that does not increase healthcare costs, is accessible to all surgical centres and can be adapted to each specific environment. OBJECTIVES: To evaluate the effectiveness of establishing a modified WHO SSC on the safety and quality of care of the neurosurgical patient in a third-level university hospital. MATERIAL AND METHODS: The SSC was applied to a series of 400 scheduled surgeries between May 2009 and May 2010. During the initial 6 months, 183 surgical procedures were performed (group 1). All adverse events detected in this period were studied with a root-cause analysis methodology (RCA) and, according to its results, corrective measures were introduced. After that, 217 procedures were performed (group 2). RESULTS: We recorded 51 events in 44 surgeries (11%). We were able to correct 88.23% of them before surgery was initiated, avoiding any consequence in the normal management of the case. In Group 1, incidents were noted in 15.3% of the procedures. The RCA suggested that 37.8% of the events had a human cause, followed by problems related to material resources and equipment in 29.7%, and organisational reasons in 21.6%. Incidence of events was reduced in group 2 to 7.4% (P=.01). Corrective measures prevented the appearance of perioperative events in 1 out of 13 procedures. CONCLUSIONS: The SSC is an effective tool for improving safety in neurosurgical patients, which can be established in surgical departments of any hospital without increasing healthcare costs or operative time.

Cortex-sparing fiber dissection: an improved method for the study of white matter anatomy in the human brain.

Classical fiber dissection of post mortem human brains enables us to isolate a fiber tract by removing the cortex and overlying white matter. In the current work, a modification of the dissection methodology is presented that preserves the cortex and the relationships within the brain during all stages of dissection, i.e. 'cortex-sparing fiber dissection'. Thirty post mortem human hemispheres (15 right side and 15 left side) were dissected using cortex-sparing fiber dissection. Magnetic resonance imaging study of a healthy brain was analyzed using diffusion tensor imaging (DTI)-based tractography software. DTI fiber tract reconstructions were compared with cortex-sparing fiber dissection results. The fibers of the superior longitudinal fasciculus (SLF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF) were isolated so as to enable identification of their cortical terminations. Two segments of the SLF were identified: first, an indirect and superficial component composed of a horizontal and vertical segment; and second, a direct and deep component or arcuate fasciculus. The IFOF runs within the insula, temporal stem and sagittal stratum, and connects the frontal operculum with the occipital, parietal and temporo-basal cortex. The UF crosses the limen insulae and connects the orbito-frontal gyri with the anterior temporal lobe. Finally, a portion of the ILF was isolated connecting the fusiform gyrus with the occipital gyri. These results indicate that cortex-sparing fiber dissection facilitates study of the 3D anatomy of human brain tracts, enabling the tracing of fibers to their terminations in the cortex. Consequently, it is an important tool for neurosurgical training and neuroanatomical research.

Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review. / La estimulación cerebral profunda en el trastorno obsesivo-compulsivo refractario al tratamiento: una revisión sistemática.

INTRODUCTION: At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. METHOD: We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. RESULTS: The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. CONCLUSIONS: The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit.

Stimulus-Evoked Electromyographic Monitoring During Minimally Invasive Transpedicular Implantation of Screws in Lumbosacral Spine: Threshold Value, Methodology and Clinical Effectiveness.

BACKGROUND: Stimulus-evoked electromyography (EMG) has been developed to increase the safety of transpedicular placement of screws. There is more consensus about this monitoring method in open surgery. Alarm thresholds for minimally invasive surgery are based on referential value for open surgery. Nevertheless, there are no uniform alarm criteria on this modality for minimally invasive surgery. Using an analysis of alarm threshold, methodology and clinical effectiveness on stimulus-evoked EMG monitoring for minimally invasive transpedicular implantation of screws in the lumbosacral spine, this study aims to reflect and recommend for optimizing accuracy. METHODS: Using a selection of studies, an analysis of the pedicle breach rates and breach-related clinical complication rates was made between studies on minimally invasive surgery by applying different thresholds. A second analysis of the pedicle breach rates and breach-related clinical complication rates was made between studies on open and minimally invasive surgery by applying the same threshold. RESULTS: In minimally invasive surgery, stimulus-evoked EMG has an acceptable accuracy in the detection of clinical relevant pedicle breaches. Suction limitation may alter the stimulation threshold. No significant differences in clinical effectiveness were observed between studies by applying thresholds of 5 mA, 7 mA, and 12 mA. However, a low threshold of 5 mA seems inappropriate for the tap stimulation. CONCLUSION: In minimally invasive surgery, continuous stimulation of instrumentation devices is recommended. A minimum 5-mA threshold should be used for stimulation of the pedicle access needle. Use of higher-stimulation thresholds during tapping and incorporation of an adapted continuous suction system may optimize the accuracy of stimulus-evoked EMG.

Recovery of long-term paresis following resection of WHO grade II gliomas infiltrating the pyramidal pathway.

Recent publications had reported high rates of preoperative neurological impairments in WHO grade II gliomas (GIIG) that significantly affect the quality of life. Consequently, one step further in the analysis of surgical outcome in GIIG is to evaluate if surgery is capable to improve preoperative deficits. Here are reported two cases of GIIG infiltrating the primary motor cortex and pyramidal pathway that had a long-term paresis before surgery. Both patients were operated with intraoperative electrical stimulation mapping, with identification and preservation of the primary motor cortex and pyramidal tract. Despite the long-lasting paresis, both cases had a significant improvement of motor function after surgery. Knowledge of this potential recovery before surgery is of major significance for planning the surgical strategy in GIIG. Two possible predictors of motor recovery were analyzed: 1) reconstruction of the corticospinal tract with diffusion tensor imaging tractography is indicative of anatomo-functional integrity, despite tract deviation and infiltration; 2) intraoperative identification of motor response by electrostimulation confirms the presence of an intact peritumoral tract. Thus, resection should stop at this boundary even in cases of long lasting preoperative hemiplegia.

[A very slow-growing exophytic hemisphere glioma: a case report]. / Glioma exofítico hemisférico de muy lento crecimiento: a propósito de un caso.

INTRODUCTION: Gliomas are characterized by a infiltrative pattern of growth, with cellular migration along the white matter fiber tracts, exophytic growth in low-grade gliomas has not been described yet. A case of hemispheric glioma with slow growing and an exophytic component is presented. CASE REPORT: 55 year-old male, with motor partial seizures. MRI shows a WHO grade II oligodendroglioma infiltrating the superior frontal gyrus with exophytic extension above the precentral gyrus. Clinical and radiological follow-up was performed for 23 years. Volumetric assessment of tumor progression revealed a growth rate of 0.5 mm per year. Surgical dissection revealed that the precentral gyrus was displaced inferiorly by the tumor, and a clear subarachnoid plane separated both structures. Functional areas were not identified within the exophytic component. Postoperative neurological deficits were not observed. CONCLUSIONS: The growth rate in low-grade gliomas has been estimated between 4 and 6 mm per year. The tumor described here had a growth rate of 0.5 mm per year, far below this average. Preoperative identification of this exophytic growth pattern is of major significance for surgical planning. The exophytic tumor is amenable for a safe and complete resection as it is covered by the arachnoid and pial membranes of the cistern and the surrounding brain.

TITLE: Glioma exofitico hemisferico de muy lento crecimiento: a proposito de un caso.Introduccion. Los gliomas de bajo grado presentan un patron de crecimiento caracteristico a traves de las fibras de la sustancia blanca. El crecimiento exofitico en gliomas de bajo grado hemisfericos no se ha descrito previamente. Se presenta un caso de glioma hemisferico de lenta progresion y con crecimiento exofitico. Caso clinico. Varon de 55 años, con crisis parciales motoras secundarias a un oligodendroglioma de grado II de la Organizacion Mundial de la Salud. El tumor infiltraba la circunvolucion frontal superior con extension exofitica que se extendia por encima de la circunvolucion precentral. Fue seguido con controles clinicorradiologicos durante 23 años. El analisis de la evolucion radiologica del tumor demostraba un crecimiento tumoral lento, con una velocidad de crecimiento de 0,5 mm al año. Durante la exeresis quirurgica se definio un plano subaracnoideo entre el componente exofitico y la circunvolucion precentral, que se encontraba desplazada inferiormente sin infiltracion tumoral. La estimulacion electrica intraoperatoria no evidencio funcion en el componente exofitico, pero si en la circunvolucion precentral. No se observaron deficits neurologicos postoperatorios. Conclusiones. La velocidad de crecimiento en gliomas de bajo grado se ha estimado en 4-6 mm al año. El tumor que se describe aqui tiene una velocidad de crecimiento de 0,5 mm al año, muy por debajo de esta media. La identificacion de la porcion exofitica es un paso importante en la planificacion preoperatoria. Este componente es mas facil de resecar debido al plano de clivaje subaracnoideo y a la ausencia de funcion.

Insular Gliomas with Exophytic Extension to the Sylvian Cistern: A Glioma Growth Pattern That Has Gone Previously Unnoticed.

BACKGROUND: An exophytic tumor is defined as a tumor that has its epicenter in the nervous tissue but grows outside the anatomical superficial boundaries of the brain within an adjacent space. Exophytic extension of hemispheric gliomas is extremely rare. The object of this study is to describe the exophytic growth pattern of insular gliomas. METHODS: A series of 28 insular gliomas operated on consecutively were analyzed. The definition of exophytic glioma included these 2 criteria: 1) preoperative magnetic resonance imaging with evidence of exophytic local tumor extension outside the anatomical superficial boundaries of the brain; and 2) surgical identification of piamater and arachnoid invasion, with tumor growth to the adjacent cisterns. RESULTS: A series of 6 exophytic gliomas (21.4%) are reported, among a series of 28 consecutive insular gliomas operated. The exophytic component originated from the posterior portion of the basal frontal lobe, with extension to the sphenoidal compartment of the sylvian cistern, reaching the temporal pole. All exophytic tumors were type 5A in Yasargil classification. The histologic diagnosis was World Health Organization grade II glioma in 3 cases and anaplastic glioma in 3 cases. All patients underwent surgery, and the exophytic component was removed completely. CONCLUSIONS: Radiologic features that define the exophytic growth pattern in insular gliomas are the posterior displacement of the middle cerebral artery and a sharp subarachnoid margin that separates the exophytic tumor from the temporal pole. Contrary to the tumor that infiltrates the anterior perforating substance, the exophytic tumor is amenable for safe and complete resection.

Incidence of Idiopathic Normal-Pressure Hydrocephalus in Northern Spain.

BACKGROUND: Although the incidence of idiopathic normal-pressure hydrocephalus (iNPH) can be 1.20 cases/1000 inhabitants/year in individuals ≥ 70 years old, in most series, the incidence of shunt-responsive iNPH appears to be <1/100,000 inhabitants/year. We report the results of a prospective 10-year longitudinal study of the incidence of iNPH in a northern Spanish population. METHODS: In a stable population of 590,000 inhabitants served by a single neurosurgical department, we periodically asked all primary care practitioners, neurologists, and geriatricians to refer for iNPH screening any patient with ventricular dilation who was complaining of motor disturbances, cognitive impairment, or sphincter dysfunction. RESULTS: From January 2003 to December 2012, 293 patients were referred with suspected normal-pressure hydrocephalus. In 187 patients, iNPH was diagnosed; 89 of these patients were classified as probable iNPH, and 98 were classified as possible iNPH. Cerebrospinal fluid diversion was performed in 152 patients, and 119 showed a good outcome. The incidence of iNPH was significantly greater in male patients and patients >60 years old and increased exponentially with age. After age 60, the standardized age- and sex-adjusted incidence rates for iNPH, shunt surgery for iNPH, and shunt-responsive iNPH were 13.36 cases/100,000 inhabitants/year, 10.85 cases/100,000 inhabitants/year, and 8.55 cases/100,000 inhabitants/year. No differences were detected in the response rate between probable and possible iNPH (80.52% vs. 76.00%; P = 0.497). CONCLUSIONS: Even with a protocol for patient referral in place, reported iNPH incidence was lower than predicted, reflecting a persistent problem of underdiagnosis in our population.

Epidemiology of Idiopathic Normal Pressure Hydrocephalus: A Systematic Review of the Literature.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is an important cause of gait disturbance and cognitive impairment in elderly adults. However, the epidemiology of iNPH is relatively unknown, largely as a result of the paucity of specifically designed population studies. This systematic review aims to assess the prevalence and incidence of iNPH. METHODS: A systematic literature review on the epidemiology of iNPH was conducted using MEDLINE/PubMed searching for articles published up to June 2014. RESULTS: The inclusion criteria were met by 21 studies. Of the studies, 12 were specifically designed for detecting cases of iNPH; however, only 4 were prospective. In people >65 years old, pooled prevalence obtained from specific population studies was 1.3%, which was almost 50-fold higher than that inferred from door-to-door surveys of dementia or parkinsonism. Prevalence may be higher in assisted-living and extended-care residents, with 11.6% of patients fulfilling the criteria for suspected iNPH and 2.0% of patients showing permanent improvement after cerebrospinal fluid diversion. The only prospective population-based survey that reported iNPH incidence estimated 1.20 cases/1000 inhabitants/year, 15-fold higher than estimates obtained from studies based on hospital catchment areas. The incidence of shunt surgery for iNPH and shunt-responsive iNPH obtained from incident cases of hospital catchment areas appears to be <2 cases/100,000 inhabitants/year and 1 case/100,000 inhabitants/year, respectively. No population-based study reporting the real values for these 2 parameters could be found. CONCLUSIONS: iNPH appears to be extremely underdiagnosed. Properly designed and adequately powered population-based studies are required to characterize the epidemiology of this disease accurately.

Subcortical anatomy as an anatomical and functional landmark in insulo-opercular gliomas: implications for surgical approach to the insular region.

OBJECT: Little attention has been given to the functional challenges of the insular approach to the resection of gliomas, despite the potential damage of essential neural networks that underlie the insula. The object of this study is to analyze the subcortical anatomy of the insular region when infiltrated by gliomas, and compare it with the normal anatomy in nontumoral hemispheres. METHODS: Ten postmortem human hemispheres were dissected, with isolation of the inferior fronto-occipital fasciculus (IFOF) and the uncinate fasciculus. Probabilistic diffusion tensor imaging (DTI) tractography was used to analyze the subcortical anatomy of the insular region in 10 healthy volunteers and in 22 patients with insular Grade II and Grade III gliomas. The subcortical anatomy of the insular region in these 22 insular gliomas was compared with the normal anatomy in 20 nontumoral hemispheres. RESULTS: In tumoral hemispheres, the distances between the peri-insular sulci and the lateral surface of the IFOF and uncinate fasciculus were enlarged (p < 0.05). Also in tumoral hemispheres, the IFOF was identified in 10 (90.9%) of 11 patients with an extent of resection less than 80%, and in 4 (36.4%) of 11 patients with an extent of resection equal to or greater than 80% (multivariate analysis: p = 0.03). CONCLUSIONS: Insular gliomas grow in the space between the lateral surface of the IFOF and uncinate fasciculus and the insular surface, displacing and compressing the tracts medially. Moreover, these tracts may be completely infiltrated by the tumor, with a total disruption of the bundles. In the current study, the identification of the IFOF with DTI tractography was significantly associated with the extent of tumor resection. If the IFOF is not identified preoperatively, there is a high probability of achieving a resection greater than 80%.

Culture dimensionality influences the resistance of glioblastoma stem-like cells to multikinase inhibitors.

Sunitinib, an inhibitor of kinases, including VEGFR and platelet-derived growth factor receptor (PDGFR), efficiently induces apoptosis in vitro in glioblastoma (GBM) cells, but does not show any survival benefit in vivo. One detrimental aspect of current in vitro models is that they do not take into account the contribution of extrinsic factors to the cellular response to drug treatment. Here, we studied the effects of substrate properties including elasticity, dimensionality, and matrix composition on the response of GBM stem-like cells (GSC) to chemotherapeutic agents. Thirty-seven cell cultures, including GSCs, parenchymal GBM cells, and GBM cell lines, were treated with nine antitumor compounds. Contrary to the expected chemoresistance of GSCs, these cells were more sensitive to most agents than GBM parenchymal cells or GBM cell lines cultured on flat (two-dimensional; 2D) plastic or collagen-coated surfaces. However, GSCs cultured in collagen-based three-dimensional (3D) environments increased their resistance, particularly to receptor tyrosine kinase inhibitors, such as sunitinib, BIBF1120, and imatinib. Differences in substrate rigidity or matrix components did not modify the response of GSCs to the inhibitors. Moreover, the MEK-ERK and PI3K-Akt pathways, but not PDGFR, mediate at least in part, this dimensionality-dependent chemoresistance. These findings suggest that survival of GSCs on 2D substrates, but not in a 3D environment, relies on kinases that can be efficiently targeted by sunitinib-like inhibitors. Overall, our data may help explain the lack of correlation between in vitro and in vivo models used to study the therapeutic potential of kinase inhibitors, and provide a rationale for developing more robust drug screening models.

Fiber dissection and diffusion tensor imaging tractography study of the temporoparietal fiber intersection area.

BACKGROUND: Lesion studies and recent surgical series report important sequelae when the inferior parietal lobe and posterior temporal lobe are damaged. Millions of axons cross through the white matter underlying these cortical areas; however, little is known about the complex organization of these connections. OBJECTIVE: To analyze the subcortical anatomy of a specific region within the parietal and temporal lobes where 7 long-distances tracts intersect, ie, the temporoparietal fiber intersection area (TPFIA). METHODS: Four postmortem human hemispheres were dissected, and 4 healthy hemispheres were analyzed through the use of diffusion tensor imaging--based tractography software. The different tracts that intersect at the posterior temporal and parietal lobes were isolated, and the relations with the surrounding structures were analyzed. RESULTS: Seven tracts pass through the TPFIA: horizontal portion of the superior longitudinal fasciculus, arcuate fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, optic radiations, and tapetum. The TPFIA was located deep to the angular gyrus, posterior portion of the supramarginal gyrus, and posterior portion of the superior, middle, and inferior temporal gyri. CONCLUSION: The TPFIA is a critical neural crossroad; it is traversed by 7 white matter tracts that connect multiple areas of the ipsilateral and contralateral hemisphere. It is also a vulnerable part of the network in that a lesion within this area will produce multiple disconnections. This is valuable information when a surgical approach through the parieto-temporo-occipital junction is planned. To decrease surgical risks, a detailed diffusion tensor imaging tractography reconstruction of the TPFIA should be performed, and intraoperative electric stimulation should be strongly considered.