Metabolomic characterization of human hippocampus from drug-resistant epilepsy with mesial temporal seizure.

OBJECTIVE: Within a complex systems biology perspective, we wished to assess whether hippocampi with established neuropathological features have distinct metabolome. Apparently normal hippocampi with no signs of sclerosis (noHS), were compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2). Hippocampus metabolome from patients with epilepsy-associated neuroepithelial tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs), was also compared to noHS epileptiform tissue. METHODS: All patients underwent standardized temporal lobectomy. We applied 1 H high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy to 48 resected human hippocampi. NMR spectra allowed quantification of 21 metabolites. Data were analyzed using multivariate analysis based on mutual information. RESULTS: Clear distinct metabolomic profiles were observed between all studied groups. Sixteen and 18 expected metabolite levels out of 21 were significantly different for HS1 and HS2, respectively, when compared to noHS. Distinct concentration variations for glutamine, glutamate, and N-acetylaspartate (NAA) were observed between HS1 and HS2. Hippocampi from GG and DNT patients showed 7 and 11 significant differences in metabolite concentrations when compared to the same group, respectively. GG and DNT had a clear distinct metabolomic profile, notably regarding choline compounds, glutamine, glutamate, aspartate, and taurine. Lactate and acetate underwent similar variations in both groups. SIGNIFICANCE: HRMAS NMR metabolomic analysis was able to disentangle metabolic profiles between HS, noHS, and epileptic hippocampi associated with EANT. HRMAS NMR metabolomic analysis may contribute to a better identification of abnormal biochemical processes and neuropathogenic combinations underlying mesial temporal lobe epilepsy.

Flow control using Scepter™ balloons for Onyx embolization of a vein of Galen aneurysmal malformation.

PURPOSE: We present a technical development of the endovascular treatment technique for vein of Galen aneurysmal malformation, using Onyx™ (ethylene vinyl alcohol copolymer) delivered under flow control through double-lumen balloon microcatheters. MATERIALS AND METHODS: An 11-month-old patient that initially presented with increasing head circumference was diagnosed with mural type vein of Galen aneurysmal malformation. Complete cure was obtained in a single endovascular treatment session. Onyx was delivered simultaneously through two double-lumen balloon microcatheters (Scepter™, Microvention, Terumo Group). In both arterial feeders, balloon inflation occluded the high-flow arterial-venous shunting and thus facilitated the controlled propagation of the embolic product in the afferent artery and the shunt point while preventing distal migration into the venous system. RESULTS: Two years post-procedure, MR imaging showed persistent occlusion of arterial-venous shunts with complete regression of the venous dilatation. On clinical examination, the patient had no neurological deficits, and no cognitive impairment was detected at neuropsychological testing. CONCLUSION: The use of double-lumen balloon microcatheters for flow control during delivery of Onyx represents a viable alternative for the endovascular treatment of vein of Galen aneurysmal malformations.

Neural tube defects: the experience of the registry of congenital malformations of Alsace, France, 1995-2009.

CONTEXT AND OBJECTIVE: Considering the lack of accurate and up-to-date information available about neural tube defects (NTDs) in France, the purpose of this study was to review clinical and epidemiological data of NTDs and to evaluate the current efficiency of prenatal diagnosis in Alsace (northeastern France). METHODS: A population-based retrospective study was performed from data of the Registry of Congenital Malformations of Alsace between 1995 and 2009. Data were analyzed as a whole and according to the anatomical type of the malformation (anencephaly, cephalocele and spina bifida). Statistical analyses were carried out using the Statistical Package for the Social Sciences. RESULTS: 272 NTDs were recorded divided in 113 cases of anencephaly (42%), 35 cases of cephalocele (13%) and 124 cases of spina bifida (45%). The total prevalence at birth of 14/10,000 (95% CI 13-16) was stable throughout the reporting period. A chromosome abnormality was identified in 27 cases (12% of all karyotyped cases). NTDs were prenatally diagnosed by ultrasound in 88% of the cases. The mean age upon prenatal diagnosis slightly declined during the 15-year period, significantly for spina bifida only. The global rate of terminations of pregnancy following prenatal diagnosis was 97% (230/238). CONCLUSION: This work constitutes a unique population-based study providing accurate and specific up-to-date data from a unique center over a longer period (1995-2009). The most important information concerns the high and stable prevalence, which calls into question the efficiency of the primary prevention by folic acid supplementation and the efficiency of prenatal diagnosis.

Endoscopic endonasal approach in the management of skull base chordomas--clinical experience on a large series, technique, outcome, and pitfalls.

Skull base chordomas represent very interesting neoplasms, due to their rarity, biological behavior, and resistance to treatment. Their management is very challenging. Recently, the use of a natural corridor, through the nose and the sphenoid sinus, improved morbidity and mortality allowing also for excellent removal rates. Prospective analysis of 54 patients harboring a skull base chordoma that were managed by extended endonasal endoscopic approach (EEA). Among the 54 patients treated (during a 72 months period), 21 were women and 33 men, undergoing 58 procedures. Twenty-two cases (40%) were recurrent and 32 (60%) newly diagnosed chordomas. Among the 32 newly diagnosed chordomas, a gross total resection was achieved in 28 cases (88%), a near total (>95% of tumor) in 2 cases (6%), a partial (>50% of tumor) in 2 cases (6%). Among the 22 recurrent chordomas, resection was complete in 7 cases (30%), near total in 7 (30%), and partial in 8 (40%). The global gross total resection rate was 65% (35/54 cases). Four patients (11%) recurred and 4 (11%) progressed within a mean follow-up of 34 months (range 12-84 months). Four patients (11%) were re-operated; one patient (1.8%) died due to disease progression, one patient (1.8%) died 2 weeks after surgery due to a massive bleeding from an ICA pseudo aneurysm. CSF leakage occurred in four patients (8%), and meningitis in eight cases (14%). No new permanent neurological deficit occurred. The EEA management of skull base chordomas requires a long and gradual learning curve that once acquired offers the possibility of either similar or better resection rates as compared to traditional approaches while morbidity is improved.

Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis.

Gelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a "hypothalamic plus" epilepsy. "Hypothalamic plus" epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent two-step surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure-free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans.

Temporal lobe association fiber tractography as compared to histology and dissection.

OBJECTIVES: To compare the temporal lobe white matter fiber bundles obtained by diffusion tensor imaging-based tractography to that by histology and dissection, and to study the interindividual variability of the obtained tracts. MATERIALS AND METHODS: DTI (diffusion tensor imaging) acquisitions (30 directions) were obtained from nine healthy volunteers. Imaging post-processing was performed with FSL (FMRIB Software Library) software. Uncinate fasciculus, longitudinal inferior fasciculus and optic radiations were tracked after positioning of the region of interest (ROI) in predetermined anatomical landmarks. Histological data were obtained by cutting 15 µm coronal sections in one left brain hemisphere and staining with modified Heidenhain-Woelcke myelin stain. Dissection was performed on the left brain hemisphere prepared in accordance with the Klingler method. Tractography of each bundle was compared to histology and dissection data. To highlight the interindividual variability of the considered fiber tracts, all the images were affinely registered on an arbitrarily chosen reference image by considering the B0 images. Fiber tracts were then warped according to the corresponding estimated transformation and an average fiber tract image was then computed. RESULTS: Our results demonstrated a good concordance between tractography of the temporal lobe white matter bundles and dissection and histological data. The interindividual reproducibility of each tract seemed to be good, particularly in the middle part. The variability was more important at both ends, probably in relation to the dispersion of fiber bundles. CONCLUSION: Diffusion tensor imaging-based tractography of temporal lobe white matter tracts seemed to be in accordance with histological and dissection data. Taking into account some limitations, it could be of particular interest for the presurgical planning of temporal lobectomy.

Do medulloblastoma tumors meet the Food and Drug Administration criteria for anti-erbB2 therapy with trastuzumab?

Several publications have recently focused on the erbB2 receptor in pediatric medulloblastomas (MBs) and its prognostic consequence. We determined erbB2 expression in 23 MBs at diagnosis. After DNA extraction, quantitative PCR targeting the erbB2 gene was performed and correlated with FISH analysis and immunohistochemistry. The samples were representative of the spectrum of the disease apart from the absence of large cell MBs. Using the tools validated for breast cancers by the FDA, we did not observe any expression or amplification of erbB2 and hence we speculate that MBs are not a good target for treatment with anti-erbB2 antibodies.

Spontaneous spinal epidural hematomas in children: can we prevent a negative prognosis?--reflections on 2 cases.

Spontaneous spinal epidural hematomas in children are very rare and, until now, have not been described in infants. Spontaneous spinal epidural hematomas is characterized by a sudden onset of acute back pain followed by acute neurological deterioration within a few hours, but in younger children the initial symptoms are often nonspecific, leading to a delay in diagnosis and treatment. Although some cases have been reported, controversy persists as to its origin, diagnosis, and timing of treatment. We present 2 new cases of this rare condition: a 7-month-old girl who suffered from acute paraplegia and, unfortunately, did not recover after adequate spinal decompression. To our knowledge, this is the first reported case of spontaneous spinal epidural hematomas in an infant. We also report a similar observation in a 13.5-year-old boy who also suffered from acute paraplegia and had only a partial recovery after urgent decompression.

Altered expression of alpha3-containing GABAA receptors in the neocortex of patients with focal epilepsy.

Impaired transmission in GABAergic circuits is thought to contribute to the pathogenesis of epilepsy. Although it is well established that major reorganization of GABA(A) receptor subtypes occurs in the hippocampus of patients with medically refractory temporal lobe epilepsy (TLE), it is unclear whether this disorder is also associated with alterations in GABA(A) receptor subtypes in the neocortex. Here we have investigated immunohistochemically the subunit composition and neocortical distribution of three major GABA(A) receptor subtypes using antibodies specifically recognizing the subunits alpha1, alpha2, alpha3, beta2/3 and gamma2. Cortical tissue was obtained at surgery from patients with TLE and hippocampal sclerosis (HS; n = 9), TLE associated with neocortical lesions (non-HS; n = 12) and frontal lobe epilepsy (FLE; n = 5), with post-mortem samples serving as controls (n = 4). A distinct laminar and neuronal expression pattern of the alpha-subunit variants was found across the neocortical regions examined in the temporal and frontal lobes in both control and patient tissue samples. In the five patients with FLE, GABA(A) receptor subunit staining was unchanged as compared to controls. In patients with TLE we observed a marked decrease in alpha3-subunit staining in the superficial neocortical layers (I-III), but no change in the deep layers (V and VI) or in the expression pattern of the alpha1 and alpha2-subunits. Reduced expression in alpha3-containing GABA(A) receptors was detected in six out of nine patients of the HS group and four out of twelve patients of the non-HS group. Histopathological changes were present in eight out of the ten patients with decreased alpha3-subunit staining. The selective reduction in alpha3-containing GABA(A) receptors was confirmed using semiquantitative measurements of optical density (OD). The specific changes unique to alpha3-subunit expression in the superficial neocortical layers of patients with TLE suggest that this subtype is of particular significance in the reorganization of cortical GABAergic systems in focal epilepsy.

Atonic seizures in children with surgically remediable epilepsy: a motor system seizure phenotype?

Atonic seizures are common in some epileptic syndromes beginning in infancy or early childhood but they are rarely described in epilepsy with focal seizures of structural aetiology. We aimed to characterize the electroclinical features of atonic seizures in surgically remediable paediatric patients and to study the spatiotemporal organization of the underlying epileptogenic networks. We retrospectively analysed two consecutive, longitudinally evaluated and surgically treated paediatric patients presenting with atonic seizures as a manifestation of pharmacoresistant epilepsy of structural aetiology, evidenced by scalp- and stereotactic intracerebral video-EEG-recordings. A quantitative analysis of the epileptogenic zone organization was performed using the "epileptogenicity index". Long-lasting generalized ictal atonia, occurring in infancy, was a predominant clinical feature in both patients, with some hints of focal origin present in one case. The seizure phenotype evolved at later age into subtle segmental atonia, associated with prominent positive motor signs. The epileptogenic zone was localized within the dorsolateral or mesiolateral premotor region. Its spatial organization was focal, matching the lesional cortex in one and distributed involving several lesional and non-lesional structures in the other case. The emergence of atonic semiology temporally correlated with involvement of both lateral and mesial premotor, as well as primary motor areas. We hypothesize that atonic seizures may be considered as a motor system seizure phenotype in the setting of structural epilepsy. Complete removal of the epileptogenic area provided excellent seizure control.

Towards a definition of the "practical" epileptogenic zone: a case of epilepsy with dual pathology.

Presurgical evaluation for patients with drug-resistant epilepsy requires the definition of various zones that have a variable spatial relationship with the epileptogenic zone. All the available methods to directly measure the actual seizure-onset zone and to define "the minimum amount of cortical tissue that must be resected to produce seizure-freedom" have significant limitations. We report on the case of a patient with dual pathology (hippocampal sclerosis and a post-traumatic scar) and discuss the contribution of the various presurgical investigations that led to surgery and seizure-freedom.

Selective memory impairment for public events in a patient with left temporal lobe epilepsy.

Highly selective memory impairment for public events was demonstrated in a patient (JR), who suffered from temporal lobe epilepsy (TLE). We successfully trained JR's memory for a set of news events and discuss, on those bases, the characteristics of news events processing that may have contributed to its increased vulnerability relative to autobiographical memory (AbM).

Balloon protection of the Labbé vein during transarterial embolization of a dural arterio-venous fistula.

INTRODUCTION: Endovascular treatment of type III dural arterio-venous fistulas can be challenging if the fistulous point is close to a functionally important cortical vein. METHODS: A technique is described for temporary balloon protection of the vein of Labbé during transarterial Onyx embolization of a type III dural arterio-venous fistula. One illustrative case is presented. Careful anatomic consideration of the concerned venous segment (at the insertion point into the lateral sinus) and the choice of balloon minimized the risk of venous rupture. RESULTS: Using this method, satisfactory progression of Onyx was obtained within the arterio-venous shunt while preserving the patency of the Labbé vein. CONCLUSION: Temporary balloon protection of the Labbé vein is a feasible option to preserve its patency during embolization of dural arterio-venous fistulas. To the authors' knowledge, this is the first report on the use of temporary balloon protection of a cortical vein.

Giant postsurgical pseudomeningocele by SPECT/CT cisternography.

We describe a case of a 32-year-old man with a giant pseudomeningocele seen on MRI examination 6 months after spinal surgery. Radionuclide SPECT/CT cisternography performed after intrathecal suboccipital injection of In-DTPA identified the site of cerebral spinal fluid leak at the L4 level, and the patient underwent surgical correction of the dural defect. A repeat MRI examination 8 months later showed no signs of recurrence.

Surgical management of spinal dural arteriovenous fistulas.

Spinal dural arteriovenous fistulas are the most common type of spinal arteriovenous malformations. Treatment options consist of microsurgical exclusion and/or endovascular embolization. We retrospectively identified all patients who benefited from surgical treatment at our tertiary center between January 2001 and December 2008. Clinical and imaging data were collected from patient files, including pre- and post-operative formal neurological examination, complete spine MRI and spinal digital subtraction angiography. Of our 30 patients, 25 were men and five were women with a median age of 62 years (range 24-76). The average delay between symptom onset and clinical diagnosis was 27 months (range 1-90). Complete cure of the fistula was obtained in all patients in a single surgical session with no procedural complications and no surgical morbidity. After a mean follow-up period of 32 months (range 14-128), 25 patients (83%) had improved, four were stable and one worsened. Despite recent advances in endovascular techniques and materials, there is a subgroup of patients for which surgery remains the best treatment option. Careful patient selection, a multidisciplinary approach and standardized surgical techniques can lead to excellent results with virtually no complications.

[Brain metastases: a neurosurgical point of view]. / Les métastases cérébrales: le point de vue du neurochirurgien.

The question of accessibility to the recent development of diagnostic and therapeutic tools for brain metastasis patients remains a problem. Advances in neurosurgery, new fields in chemotherapy, radiosurgery and different types of radiation therapy are accompanied by the need of dedicated staff time and materials. The limits of what we can offer to our patients regarding access to treatment and costs have to be clarified through a national consensus. Multimodal strategies must take in account the individual patient as well as accessibility to the different treatment tools. The most important problem remain the ongoing need for radiosurgery and various subtype of new radiotherapy methods.

Supraorbital eyebrow approach to skull base lesions.

We report our experience with a supraorbital eyebrow minicraniotomy. This technique is suitable to lesions situated in the region of the anterior fossa, suprasellar cisterns, parasellar region and Sylvian fissure. A 50 mm incision in the eyebrow and a supraorbital minicraniotomy is performed. Sixteem patients harboring different lesions were operated on with good postoperative and cosmetic results. We conclude that this approach is safe and useful in selected cases.

Posterior atlanto-occipital and atlanto-axial area and its surgical interest.

UNLABELLED: Classic anatomical studies describe two membranes - atlanto-occipital and atlanto-axial in the posterior aspect of the craniocervical region. During many surgical procedures in this area, however, we have not found such membranes. OBJECTIVE: To clarify the anatomical aspects and structures taking part of the posterior atlanto-occipital and atlanto-axial area. METHOD: Analysis of histological cuts of three human fetuses and anatomical studies of 8 adult human cadavers. RESULTS: In both atlanto-occipital and atlanto-axial areas, we have observed attachment between suboccipital deep muscles and the spinal cervical dura. However, anatomical description of such attachments could not be found in textbooks of anatomy. CONCLUSION: Our study shows the absence of the classical atlanto-occipital and atlanto-axial membranes; the occipito-C1 and C1-C2 posterior intervals are an open area, allowing aponeurotic attachment among cervical dura mater and posterior cervical muscles.

Endovascular treatment in two cases of bilateral ischemic stroke.

Acute bilateral intracranial large artery occlusion is a rare occurrence that can lead to bihemispheric ischemia and potentially devastating functional consequences. We discuss two cases that initially presented with unilateral symptoms and did not show signs of bilateral arterial occlusions on the initial MRI imaging. This became evident while performing the angiographic study at the beginning of the endovascular procedure. Both patients were successfully treated with bilateral mechanical thrombectomy as a complement to intravenous thrombolysis. We describe our method of simultaneous sequential bilateral thrombectomy. To our knowledge, this is the first report of successful endovascular therapy in bilateral ischemic stroke.