JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
7T MRI features in control human hippocampus and hippocampal sclerosis: An ex vivo study with histologic correlations.
Epilepsia
PUBLISHED: 09-05-2014
Show Abstract
Hide Abstract
Hippocampal sclerosis (HS) is the major structural brain lesion in patients with temporal lobe epilepsy (TLE). However, its internal anatomic structure remains difficult to recognize at 1.5 or 3 Tesla (T) magnetic resonance imaging (MRI), which allows neither identification of specific pathology patterns nor their proposed value to predict postsurgical outcome, cognitive impairment, or underlying etiologies. We aimed to identify specific HS subtypes in resected surgical TLE samples on 7T MRI by juxtaposition with corresponding histologic sections.
Related JoVE Video
Epilepsy surgery in children and adolescents with malformations of cortical development-Outcome and impact of the new ILAE classification on focal cortical dysplasia.
Epilepsy Res.
PUBLISHED: 06-09-2014
Show Abstract
Hide Abstract
To determine long-term efficacy and safety of epilepsy surgery in children and adolescents with malformations of cortical development (MCD) and to identify differences in seizure outcome of the various MCD subgroups. Special focus was set on the newly introduced International League Against Epilepsy (ILAE) classification of focal cortical dysplasia (FCD).
Related JoVE Video
Biochemical markers of neurodegeneration in hereditary diffuse leucoencephalopathy with spheroids.
BMJ Case Rep
PUBLISHED: 06-04-2014
Show Abstract
Hide Abstract
Hereditary diffuse leucoencephalopathy with spheroids (HDLS) is a rare autosomal dominantly inherited disease with unknown pathophysiology. Diagnosis of neurodegenerative diseases is increasingly based on biomarkers. Although lumbar puncture is routinely performed during the diagnostic workup of HDLS, reports on alterations of neurodegeneration-specific biochemical markers have not been documented so far. We report a 35-year-old woman with clinical, radiological and neuropathological signs of HDLS. She suffered from a rapidly progressive frontal lobe syndrome. Brain MRI revealed diffuse leucoencephalopathy with predominant involvement of the periventricular white matter and corpus callosum. Although she was severely impaired and leucoencephalopathy was prominent, only cerebrospinal fluid total-? was moderately elevated. Other markers of neuronal (NSE) and astrocytic (S100B) damage were within normal range. Therefore, biochemical markers of central nervous system damage are not helpful in the diagnosis of HDLS.
Related JoVE Video
Differential influence of hippocampal subfields to memory formation: insights from patients with temporal lobe epilepsy.
Brain
PUBLISHED: 05-09-2014
Show Abstract
Hide Abstract
To clarify the anatomical organization of human memory remains a major challenge in clinical neuroscience. Experimental data suggest dentate gyrus granule cells play a major role in memory acquisition, i.e. pattern separation and rapid pattern completion, whereas hippocampal CA1 neurons are implicated in place memory and autobiographical memory retrieval. Patients with temporal lobe epilepsy present with a broad spectrum of memory impairment, which can be assessed during clinical examination. Although long seizure histories may contribute to a pathophysiological reorganization of functional connectivity, surgical resection of the epileptic hippocampus offers a unique possibility to anatomically study the differential contribution of hippocampal subfields to compromised learning and memory in humans. Herein, we tested the hypothesis of hippocampal subfield specialization in a series of 100 consecutive patients with temporal lobe epilepsy submitted to epilepsy surgery. Memory profiles were obtained from intracarotid amobarbital testing and non-invasive verbal memory assessment before surgery, and correlated with histopathologically quantified cell loss pattern in hippocampal subfields obtained from the same patients using the new international consensus classification for hippocampal sclerosis proposed by the International League against Epilepsy (HS ILAE). Interestingly, patients with CA1 predominant cell loss (HS ILAE Type 2; n = 13) did not show declarative memory impairment and were indistinguishable from patients without any hippocampal cell loss (n = 19). In contrast, 63 patients with neuronal loss affecting all hippocampal subfields including CA1, CA4 and dentate gyrus (HS ILAE Type 1), or predominant cell loss in CA4 and partially affecting also CA3 and dentate gyrus (HS ILAE Type 3, n = 5) showed significantly reduced declarative memory capacities (intracarotid amobarbital testing: P < 0.001; verbal memory: P < 0.05). Our results suggested an alternative model of how memory processing can be organized amongst hippocampal subfields, and that CA1 pyramidal cells are less critically involved in declarative human memory acquisition compared to dentate gyrus granule cells or CA4/CA3 pyramidal cells.
Related JoVE Video
Sturge-Weber Syndrome Is Associated with Cortical Dysplasia ILAE Type IIIc and Excessive Hypertrophic Pyramidal Neurons in Brain Resections for Intractable Epilepsy.
Brain Pathol.
PUBLISHED: 05-04-2014
Show Abstract
Hide Abstract
Sturge-Weber syndrome (SWS) is a rare syndrome characterized by capillary-venous malformations involving skin and brain. Many patients with SWS also suffer from drug-resistant epilepsy. We retrospectively studied a series of six SWS patients with epilepsy and extensive neurosurgical resections. At time of surgery, the patients' age ranged from 11 to 35 years (with a mean of 20.2 years). All surgical specimens were well preserved, which allowed a systematic microscopical inspection utilizing the 2011 ILAE classification for focal cortical dysplasia (FCD). Neuropathology revealed dysmorphic-like neurons with hypertrophic cell bodies reminiscent to those described for FCD type IIa in all cases. However, gross architectural abnormalities of neocortical layering typical for FCD type IIa were missing, and we propose to classify this pattern as FCD ILAE type IIIc. In addition, our patients with earliest seizure onset also showed polymicrogyria (PMG; n?=?4). The ictal onset zones were identified in all patients by subdural electrodes, and these areas always showed histopathological evidence for FCD type IIIc. Four out of five patients had favorable seizure control after surgery with a mean follow-up period of 1.7 years. We concluded from our study that FCD type IIIc and PMG are frequently associated findings in SWS. FCD type IIIc may play a major epileptogenic role in SWS and complete resection of the associated FCD should be considered a prognostic key factor to achieve seizure control.
Related JoVE Video
Co-occurring malformations of cortical development and SCN1A gene mutations.
Epilepsia
PUBLISHED: 04-14-2014
Show Abstract
Hide Abstract
To report on six patients with SCN1A mutations and malformations of cortical development (MCDs) and describe their clinical course, genetic findings, and electrographic, imaging, and neuropathologic features.
Related JoVE Video
Intraoperative use of high-field MRI in hypothalamic hamartomas associated with epilepsy: clinico-pathological presentation of five adult patients.
Acta Neurochir (Wien)
PUBLISHED: 03-25-2014
Show Abstract
Hide Abstract
Hypothalamic harmartomas (HHs) are either occasionally associated with medically intractable epileptic syndromes or precocious puberty. Due to the extraordinary location and the expansive intra-axial growth, surgical resection is difficult and challenging without causing severe neurological, hypothalamic or endocrinological deficits, which account for higher mortality and morbidity.
Related JoVE Video
Cerebral cavernous malformations in the setting of focal epilepsies: pathological findings, clinical characteristics, and surgical treatment principles.
Acta Neuropathol.
PUBLISHED: 03-12-2014
Show Abstract
Hide Abstract
Cavernous cerebral malformations (CCMs) are a well-defined epilepsy-associated pathology. They represent lesions/conglomerates of abnormally configured vessels leading to seizures either as a result of physiological changes affecting the cerebral cortex immediately surrounding the CCM (an epileptogenic mechanism that is relevant for both temporal and extratemporal lesions), or as a result of promoting epileptogenicity in remote but anatomo-functionally connected brain regions (a mechanism that is particularly relevant for temporal lobe lesions). This review details the pathological findings in CCMs and discusses the mechanisms of epileptogenicity in this context. The bulk of the review will focus on therapeutic strategies. Medical therapy using antiepileptic drugs is recommended as a first-line therapy, but surgical removal of the CCM with the surrounding cortex should be pursued if seizures prove to be drug resistant. Early timing of the resection and complete removal of any associated epileptic pathology are critical for best outcomes. In addition to reviewing the available data from prior series, we present original research from two specialized epilepsy centers targeted at answering particularly pressing clinical questions mainly related to the ideal timing and extent of surgery. Further research is needed to define the best surgical strategies in patients with temporal lobe CCMs and structurally normal hippocampi.
Related JoVE Video
Comparative study of soft tissue perineurioma and meningioma using a five-marker immunohistochemical panel.
Histopathology
PUBLISHED: 01-04-2014
Show Abstract
Hide Abstract
Owing to their close embryological relationship, soft tissue perineurioma and meningioma may closely mimic each other, not only histologically but also by immunohistochemistry. We aimed to compare the frequency of perineurial marker expression in these two entities, and to determine whether somatostatin receptor 2 (SSTR2) and progesterone receptor (PR), both expressed frequently in meningiomas, are also expressed in perineuriomas.
Related JoVE Video
The overall pathological status of the left hippocampus determines preoperative verbal memory performance in left mesial temporal lobe epilepsy.
Hippocampus
PUBLISHED: 10-18-2013
Show Abstract
Hide Abstract
Studies on hippocampal cell loss in epilepsy have produced diverging evidence as to which subfields are specifically related to memory. This may be due to rather small and often heterogeneous samples, or to different memory measures. Therefore, the current study examined hippocampal cell densities and memory in a large sample of patients with solely mesial temporal lobe epilepsy (mTLE), employing measures with proven sensitivity to mesiotemporal pathology. In 104 patients who had undergone epilepsy surgery for mTLE, we evaluated the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical verbal and figural memory while controlling for side-of-surgery and hemispheric dominance. First of all, patients showed material-specific memory impairment concordant with the lateralization of epilepsy. Factor analysis of segmental cell loss revealed a single factor reflecting the overall integrity of the hippocampus. The overall pathological status of the left hippocampus correlated with verbal memory parameters (r=.28-.36, p<.05), especially when controlling for atypical hemispheric dominance (r=.33-.59, p<.05), and explained up to 33% of the observed variance. Further analyses revealed no superior role of a single subfield or cell loss pattern for memory performance. No systematic relations between neuronal cell densities of the right hippocampus and memory function were found, nor did left of right hippocampal pathology explain figural memory parameters. The results suggest that the overall pathological status of the left hippocampus - rather than a specific subfield pathology - is predictive for verbal memory in mTLE. The findings that figural memory parameters, although sensitive to right mTLE, were not related to neuronal cell densities of the right hippocampus, puts the left/right hippocampus verbal/nonverbal memory dichotomy into perspective. © 2013 Wiley Periodicals, Inc.
Related JoVE Video
Surgical management of epilepsy due to cerebral cavernomas using neuronavigation and intraoperative MR imaging.
Neurol. Res.
PUBLISHED: 09-30-2013
Show Abstract
Hide Abstract
Cure from seizures due to cavernomas might be surgically achieved dependent on both, the complete removal of the cavernoma as well as its surrounding hemosiderin rim. High field intraoperative MRI imaging (iopMRI) and neuronavigation might play a crucial role to achieve both goals. We retrospectively investigated the long-term results and impact of intraoperative 1·5T MRI (iopMRI) and neuronavigation on the completeness of surgical removal of a cavernous malformation (CM) and its perilesional hemosiderin rim as well as reduction of surgical morbidity.
Related JoVE Video
Surgical management of epilepsy due to cerebral cavernomas using neuronavigation and intraoperative MR imaging.
Neurol. Res.
PUBLISHED: 09-28-2013
Show Abstract
Hide Abstract
Cure from seizures due to cavernomas might be surgically achieved dependent on both, the complete removal of the cavernoma as well as its surrounding hemosiderin rim. High field intraoperative MRI imaging (iopMRI) and neuronavigation might play a crucial role to achieve both goals. Were trospectively investigated the long-term results and impact of intraoperative 1.5T MRI (iopMRI) andneuronavigation on the completeness of surgical removal of a cavernous malformation (CM) and its perilesional hemosiderin rim as well as reduction of surgical morbidity.METHODS: 26 patients (14 female, 12 male, mean age 39.1 years, range: 17â€"63 years) with CM related epilepsy were identified. Eighteen patients suffered from drug resistant epilepsy (69.2%). Mean duration of epilepsy was 11.9 years in subjects with drug resistant epilepsy (n=18) and 0.3 years in subjects presenting with first-time seizures (n=8). We performed 24 lesion ectomies and two lesion ectomies combined with extended temporal resections. Seven lesions were located extra temporally.RESULTS: Complete CM removal was documented by post surgical MRI in all patients. As direct consequence of io pMRI, refined surgery was necessary in 11.5% of patients to achieve complete cavernoma removal and in another 11.5% for complete resection of additional adjacent epileptogeniccortex. Removal of the hemosiderin rim was confirmed by iopMRI in 92% of patients. Two patients suffered from mild (7.7%) and one from moderate (3.8%) visual field deficits. Complete seizure control (Engel class 1A) was achieved in 80.8% of patients with a mean follow-up period of 47.7 months.DISCUSSION: We report excellent long-term seizure control with minimal surgical morbidity after completeresection of CM using our multimodal approach.
Related JoVE Video
Improved resection in lesional temporal lobe epilepsy surgery using neuronavigation and intraoperative MR imaging: Favourable long term surgical and seizure outcome in 88 consecutive cases.
Seizure
PUBLISHED: 09-24-2013
Show Abstract
Hide Abstract
To investigate the value of intraoperative MR imaging (iopMRI) combined with neuronavigation to avoid intraoperative underestimation of the resection amount during surgery of lesional temporal lobe epilepsy (LTLE) patients.
Related JoVE Video
Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.
Brain
PUBLISHED: 09-06-2013
Show Abstract
Hide Abstract
Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures.
Related JoVE Video
Neuroprotective intervention by interferon-? blockade prevents CD8+ T cell-mediated dendrite and synapse loss.
J. Exp. Med.
PUBLISHED: 09-02-2013
Show Abstract
Hide Abstract
Neurons are postmitotic and thus irreplaceable cells of the central nervous system (CNS). Accordingly, CNS inflammation with resulting neuronal damage can have devastating consequences. We investigated molecular mediators and structural consequences of CD8(+) T lymphocyte (CTL) attack on neurons in vivo. In a viral encephalitis model in mice, disease depended on CTL-derived interferon-? (IFN-?) and neuronal IFN-? signaling. Downstream STAT1 phosphorylation and nuclear translocation in neurons were associated with dendrite and synapse loss (deafferentation). Analogous molecular and structural alterations were also found in human Rasmussen encephalitis, a CTL-mediated human autoimmune disorder of the CNS. Importantly, therapeutic intervention by IFN-? blocking antibody prevented neuronal deafferentation and clinical disease without reducing CTL responses or CNS infiltration. These findings identify neuronal IFN-? signaling as a novel target for neuroprotective interventions in CTL-mediated CNS disease.
Related JoVE Video
Deep sequencing reveals increased DNA methylation in chronic rat epilepsy.
Acta Neuropathol.
PUBLISHED: 06-13-2013
Show Abstract
Hide Abstract
Epilepsy is a frequent neurological disorder, although onset and progression of seizures remain difficult to predict in affected patients, irrespective of their epileptogenic condition. Previous studies in animal models as well as human epileptic brain tissue revealed a remarkably diverse pattern of gene expression implicating epigenetic changes to contribute to disease progression. Here we mapped for the first time global DNA methylation patterns in chronic epileptic rats and controls. Using methyl-CpG capture associated with massive parallel sequencing (Methyl-Seq) we report the genomic methylation signature of the chronic epileptic state. We observed a predominant increase, rather than loss of DNA methylation in chronic rat epilepsy. Aberrant methylation patterns were inversely correlated with gene expression changes using mRNA sequencing from same animals and tissue specimens. Administration of a ketogenic, high-fat, low-carbohydrate diet attenuated seizure progression and ameliorated DNA methylation mediated changes in gene expression. This is the first report of unsupervised clustering of an epigenetic mark being used in epilepsy research to separate epileptic from non-epileptic animals as well as from animals receiving anti-convulsive dietary treatment. We further discuss the potential impact of epigenetic changes as a pathogenic mechanism of epileptogenesis.
Related JoVE Video
Frameless Stereotactic Functional Neuronavigation Combined with Intraoperative Magnetic Resonance Imaging as a Strategy in Highly Eloquent Located Tumors Causing Epilepsy.
Stereotact Funct Neurosurg
PUBLISHED: 04-30-2013
Show Abstract
Hide Abstract
Background: Intractable epilepsy due to tumors located in highly eloquent brain regions is often considered surgically inaccessible because of a high risk of postoperative neurological deterioration. Intraoperative MRI and functional navigation contribute to overcome this problem. Objectives: To retrospectively investigate the long-term results and impact of functional neuronavigation and 1.5-tesla intraoperative MRI on patients who underwent surgery of tumors associated with epilepsy located close to or within eloquent brain areas. Methods: Nineteen patients (9 female, 10 male, mean age 41.4 ± 13.4 years, 11 low-grade and 8 high-grade glial tumors) were evaluated preoperatively using BOLD imaging, diffusion-tensor imaging tractography and magnetoencephalography. Functional data were implemented into neuronavigation in this multimodal approach. Results: In 14 of 19 patients (74%), complete resection was achieved, and in 5 patients significant tumor volume reduction was accomplished. Eight of 14 (57%) complete resections were achieved only by performing an intraoperative image update. Neurological deterioration was found permanently in 2 patients. After a mean follow-up of 43.8 ± 23.8 months, 15 patients (79%) became seizure free (Engel class Ia). Conclusions: Despite the highly eloquent location of tumors causing intractable epilepsy, our multimodal approach led to complete resection in more than two-thirds of patients with an acceptable neurological morbidity and excellent long-term seizure control. © 2013 S. Karger AG, Basel.
Related JoVE Video
International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods.
Epilepsia
PUBLISHED: 04-09-2013
Show Abstract
Hide Abstract
Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug-resistant temporal lobe epilepsy (TLE). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. A task force reviewed previous classification schemes and proposes a system based on semiquantitative hippocampal cell loss patterns that can be applied in any histopathology laboratory. Interobserver and intraobserver agreement studies reached consensus to classify three types in anatomically well-preserved hippocampal specimens: HS International League Against Epilepsy (ILAE) type 1 refers always to severe neuronal cell loss and gliosis predominantly in CA1 and CA4 regions, compared to CA1 predominant neuronal cell loss and gliosis (HS ILAE type 2), or CA4 predominant neuronal cell loss and gliosis (HS ILAE type 3). Surgical hippocampus specimens obtained from patients with TLE may also show normal content of neurons with reactive gliosis only (no-HS). HS ILAE type 1 is more often associated with a history of initial precipitating injuries before age 5 years, with early seizure onset, and favorable postsurgical seizure control. CA1 predominant HS ILAE type 2 and CA4 predominant HS ILAE type 3 have been studied less systematically so far, but some reports point to less favorable outcome, and to differences regarding epilepsy history, including age of seizure onset. The proposed international consensus classification will aid in the characterization of specific clinicopathologic syndromes, and explore variability in imaging and electrophysiology findings, and in postsurgical seizure control.
Related JoVE Video
Integration of functional neuronavigation and intraoperative MRI in surgery for drug-resistant extratemporal epilepsy close to eloquent brain areas.
Neurosurg Focus
PUBLISHED: 04-03-2013
Show Abstract
Hide Abstract
The authors performed a retrospective study to assess the impact of functional neuronavigation and intraoperative MRI (iMRI) on surgery of extratemporal epileptogenic lesions on postsurgical morbidity and seizure control.
Related JoVE Video
Increased membrane shedding--indicated by an elevation of CD133-enriched membrane particles--into the CSF in partial epilepsy.
Epilepsy Res.
PUBLISHED: 07-19-2011
Show Abstract
Hide Abstract
Recent analyses provided evidence that human adult cerebrospinal fluid (CSF) in addition to soluble proteins also contains membrane particles that moreover carry the somatic stem cell marker CD133. The significance of CD133 as a potential marker of cellular proliferation, including neurogenesis, remains unresolved. As adult neurogenesis has been implicated to be induced by epileptic seizures this study investigated whether patients with partial epilepsy show a varying amount of membrane-associated CD133 in CSF as compared to healthy adults.
Related JoVE Video
Intrinsic epileptogenicity of gangliogliomas may be independent from co-occurring focal cortical dysplasia.
Epilepsy Res.
PUBLISHED: 07-05-2011
Show Abstract
Hide Abstract
Gangliogliomas are a frequent cause of drug-resistant epilepsies in children. It remains unknown, however, whether gangliogliomas are intrinsically epileptogenic or if associated lesions contribute to their high epileptogenicity, i.e. associated focal cortical dysplasia (FCD). We report on a child operated twice for drug-resistant focal seizures symptomatic of a right temporal lobe lesion. Histological examination of the first, incomplete lesionectomy revealed tumor-associated FCD Type IIIb. The child was not seizure-free, and surface as well as intracerebral recordings were obtained during a second presurgical assessment. Histopathological examination of the second operation revealed a ganglioglioma. Intralesional EEG recordings from the ganglioglioma documented rhythmic bursts of fast activity suggesting that the high epileptogenicity of gangliogliomas is related to intrinsic epileptogenic activity.
Related JoVE Video
Neuropathologic measurements in focal cortical dysplasias: validation of the ILAE 2011 classification system and diagnostic implications for MRI.
Acta Neuropathol.
PUBLISHED: 06-24-2011
Show Abstract
Hide Abstract
Focal cortical dysplasias (FCD) which represent a composite group of cortical malformations are increasingly recognized as morphological substrate for severe therapy-refractory epilepsy in children and young adults. However, presurgical evaluation remains challenging as not all FCD variants can be reliably detected by high-resolution magnetic resonance imaging (MRI). Here, we studied a cohort of 52 epilepsy patients with neuropathological evidence for FCD using the 2011 classification of the International League against Epilepsy (ILAE) and systematically analysed those histopathologic features applicable also for MRI diagnostics. Histopathologic parameters included quantitative measurements of cellular profiles, cortical thickness, heterotopic neurons in white matter, and myelination that were compared between FCD subtypes and age-/localization-matched controls (n = 36) using multivariate analysis. Dysmorphic neurons in both FCD Type II variants showed significantly increased diameter of their cell bodies and nuclei. Cortical thickness was also increased with a distinct loss of myelin content specifying FCD Type IIb from IIa. The data further suggested that myelination deficits in FCD Type IIb result from compromised oligodendroglial lineage differentiation and we concluded that the "transmantle sign" is a unique finding in FCD Type IIb. In contrast, FCD Type Ia was characterized by a smaller cortical ribbon and higher neuronal densities, but these parameters failed to reach statistical significance (considering age- and location-dependent variability in controls). All FCD variants showed abnormal grey-white matter boundaries with increased numbers of heterotopic neurons. Similar results were obtained also at deep white matter location. Thus, many FCD variants may indeed escape visual MRI inspection, but suspicious areas with increased or decreased cortical thickness as well as grey-white matter blurring may be uncovered using post-processing protocols of neuroimaging data. The systematic analysis of well-specified histopathological features could be helpful to improve sensitivity and specificity in MRI detection during pre-surgical work-up of patients with drug-resistant focal epilepsies.
Related JoVE Video
Strumpellin is a novel valosin-containing protein binding partner linking hereditary spastic paraplegia to protein aggregation diseases.
Brain
PUBLISHED: 09-09-2010
Show Abstract
Hide Abstract
Mutations of the human valosin-containing protein gene cause autosomal-dominant inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. We identified strumpellin as a novel valosin-containing protein binding partner. Strumpellin mutations have been shown to cause hereditary spastic paraplegia. We demonstrate that strumpellin is a ubiquitously expressed protein present in cytosolic and endoplasmic reticulum cell fractions. Overexpression or ablation of wild-type strumpellin caused significantly reduced wound closure velocities in wound healing assays, whereas overexpression of the disease-causing strumpellin N471D mutant showed no functional effect. Strumpellin knockdown experiments in human neuroblastoma cells resulted in a dramatic reduction of axonal outgrowth. Knockdown studies in zebrafish revealed severe cardiac contractile dysfunction, tail curvature and impaired motility. The latter phenotype is due to a loss of central and peripheral motoneuron formation. These data imply a strumpellin loss-of-function pathogenesis in hereditary spastic paraplegia. In the human central nervous system strumpellin shows a presynaptic localization. We further identified strumpellin in pathological protein aggregates in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia, various myofibrillar myopathies and in cortical neurons of a Huntingtons disease mouse model. Beyond hereditary spastic paraplegia, our findings imply that mutant forms of strumpellin and valosin-containing protein may have a concerted pathogenic role in various protein aggregate diseases.
Related JoVE Video
Low proliferation and differentiation capacities of adult hippocampal stem cells correlate with memory dysfunction in humans.
Brain
PUBLISHED: 08-18-2010
Show Abstract
Hide Abstract
The hippocampal dentate gyrus maintains its capacity to generate new neurons throughout life. In animal models, hippocampal neurogenesis is increased by cognitive tasks, and experimental ablation of neurogenesis disrupts specific modalities of learning and memory. In humans, the impact of neurogenesis on cognition remains unclear. Here, we assessed the neurogenic potential in the human hippocampal dentate gyrus by isolating adult human neural stem cells from 23 surgical en bloc hippocampus resections. After proliferation of the progenitor cell pool in vitro we identified two distinct patterns. Adult human neural stem cells with a high proliferation capacity were obtained in 11 patients. Most of the cells in the high proliferation capacity cultures were capable of neuronal differentiation (53?±?13% of in vitro cell population). A low proliferation capacity was observed in 12 specimens, and only few cells differentiated into neurons (4?±?2%). This was reflected by reduced numbers of proliferating cells in vivo as well as granule cells immunoreactive for doublecortin, brain-derived neurotrophic factor and cyclin-dependent kinase 5 in the low proliferation capacity group. High and low proliferation capacity groups differed dramatically in declarative memory tasks. Patients with high proliferation capacity stem cells had a normal memory performance prior to epilepsy surgery, while patients with low proliferation capacity stem cells showed severe learning and memory impairment. Histopathological examination revealed a highly significant correlation between granule cell loss in the dentate gyrus and the same patients regenerative capacity in vitro (r?=?0.813; P?
Related JoVE Video
Spontaneous in vitro transformation of adult neural precursors into stem-like cancer cells.
Brain Pathol.
PUBLISHED: 10-02-2009
Show Abstract
Hide Abstract
Recent studies have found that cellular self-renewal capacity in brain cancer is heterogeneous, with only stem-like cells having this property. A link between adult stem cells and cancer stem cells remains, however, to be shown. Here, we describe the emergence of cancer stem-like cells from in vitro cultured brain stem cells. Adult rat subventricular zone (SVZ) stem cells transformed into tumorigenic cell lines after expansion in vitro. These cell lines maintained characteristic features of stem-like cells expressing Nestin, Musashi-1 and CD133, but continued to proliferate upon differentiation induction. Karyotyping detected multiple acquired chromosomal aberrations, and syngeneic transplantation into the brain of adult rats resulted in malignant tumor formation. Tumors revealed streak necrosis and displayed a neural as well as an undifferentiated phenotype. Deficient downregulation of platelet-derived growth factor (PDGF) receptor alpha was identified as candidate mechanism for tumor cell proliferation, and its knockdown by siRNA resulted in a reduction of cell growth. Our data point to adult brain precursor cells to be transformed in malignancies. Furthermore, in vitro expansion of adult neural stem cells, which will be mandatory for therapeutic strategies in neurological disorders, also harbors the risk for amplifying precursor cells with acquired genetic abnormalities and induction of malignant tumors after transplantation.
Related JoVE Video
LBH589 induces up to 10-fold SMN protein levels by several independent mechanisms and is effective even in cells from SMA patients non-responsive to valproate.
Hum. Mol. Genet.
PUBLISHED: 07-07-2009
Show Abstract
Hide Abstract
Histone deacetylase inhibitors (HDACi) are potential candidates for therapeutic approaches in cancer and neurodegenerative diseases such as spinal muscular atrophy (SMA)--a common autosomal recessive disorder and frequent cause of early childhood death. SMA is caused by homozygous absence of SMN1. Importantly, all SMA patients carry a nearly identical copy gene, SMN2, that produces only minor levels of correctly spliced full-length transcripts and SMN protein. Since an increased number of SMN2 copies strongly correlates with a milder SMA phenotype, activation or stabilization of SMN2 is considered as a therapeutic strategy. However, clinical trials demonstrated effectiveness of the HDACi valproate (VPA) and phenylbutyrate only in <50% of patients; therefore, identification of new drugs is of vital importance. Here we characterize the novel hydroxamic acid LBH589, an HDACi already widely used in cancer clinical trials. LBH589 treatment of human SMA fibroblasts induced up to 10-fold elevated SMN levels, the highest ever reported, accompanied by a markedly increased number of gems. FL-SMN2 levels were increased 2-3-fold by transcription activation via SMN2 promoter H3K9 hyperacetylation and restoration of correct splicing via elevated hTRA2-beta1 levels. Furthermore, LBH589 stabilizes SMN by reducing its ubiquitinylation as well as favouring incorporation into the SMN complex. Cytotoxic effects were not detectable at SMN2 activating concentrations. Notably, LBH589 also induces SMN2 expression in SMA fibroblasts inert to VPA, in human neural stem cells and in the spinal cord of SMN2-transgenic mice. Hence, LBH589, which is active already at nanomolar doses, is a highly promising candidate for SMA therapy.
Related JoVE Video
Good interobserver and intraobserver agreement in the evaluation of the new ILAE classification of focal cortical dysplasias.
Epilepsia
Show Abstract
Hide Abstract
An International League Against Epilepsy (ILAE) consensus classification system for focal cortical dysplasias (FCDs) has been published in 2011 specifying clinicopathologic FCD variants. The aim of the present work was to microscopically assess interobserver agreement and intraobserver reproducibility for FCD categories among an international group of neuropathologists with different levels of experience and access to epilepsy surgery tissue.
Related JoVE Video
Defining clinico-neuropathological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis.
Brain Pathol.
Show Abstract
Hide Abstract
Hippocampal sclerosis (HS) is the most frequent cause of drug-resistant focal epilepsies (ie, mesial temporal lobe epilepsy with hippocampal sclerosis; mTLE-HS), and presents a broad spectrum of electroclinical, structural and molecular pathology patterns. Many patients become drug resistant during the course of the disease, and surgical treatment was proven helpful to achieve seizure control. Hence, up to 40% of patients suffer from early or late surgical failures. Different patterns of hippocampal cell loss, involvement of other mesial temporal structures, as well as temporal neocortex including focal cortical dysplasia, may contribute to the extent of the epileptogenic network and will be discussed. An international consensus is mandatory to clarify terminology use and to reliably distinguish mTLE-HS subtypes. High-resolution imaging with confirmed histopathologic diagnosis, as well as advanced neurophysiologic and molecular genetic measures, will be a powerful tool in the future to address these issues and help to predict each patients probability to control their epilepsy in mTLE-HS conditions.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.