José M. Pascual

Glutamate, Glutamine, and GABA as Substrates for the Neuronal and Glial Compartments After Focal Cerebral Ischemia in Rats

BACKGROUND AND PURPOSE Even though the utilization of substrates alternative to glucose may play an important role in the survival of brain cells under ischemic conditions, evidence on changes in substrate selection by the adult brain in vivo during ischemic episodes remains very limited. This study investigates the utilization of glutamate, glutamine, and GABA as fuel by the neuronal and glial tricarboxylic acid cycles of both cerebral hemispheres after partially reversible focal cerebral ischemia (FCI). METHODS Right hemisphere infarct was induced in adult Long-Evans rats by permanent occlusion of the right middle cerebral artery and transitory occlusion of both common carotid arteries. (1,2-13C2) acetate was infused for 60 minutes in the right carotid artery immediately after carotid recirculation had been re-established (1-hour group) or 23 hours later (24-hour group). Extracts from both cerebral hemispheres were prepared and analyzed separately by 13C nuclear magnetic resonance and computer-assisted metabolic modeling. RESULTS FCI decreased the oxidative metabolism of glucose in the brain in a time-dependent manner. Reduced glucose oxidation was compensated for by increased oxidations of (13C) glutamate and (13C) GABA in the astrocytes of the ipsilateral hemispheres of both groups. Increased oxidative metabolism of (13C) glutamine in the neurons was favored by increased activity of the neuronal pyruvate recycling system in the 24-hour group. CONCLUSIONS Data were obtained consistent with time-dependent changes in the utilization of glutamate and GABA or glutamine as metabolic substrates for the glial or neuronal compartments of rat brain after FCI.

Intraventricular craniopharyngiomas: topographical classification and surgical approach selection based on an extensive overview

SummaryBackground. This retrospective study analyzes the clinical, neuroradiological, pathological and surgical characteristics of well-described intraventricular craniopharyngiomas with the aims of: (i) critically to review the criteria used to affirm the diagnosis of an intraventricular location (ii) defining more accurately this topographical diagnosis preoperatively, and (iii) to investigate factors influencing the surgical outcome.Method. Clinical, neuroradiological, pathological and surgical objective data of 104 well-described intraventricular craniopharyngiomas (IVC) reported in the literature, in addition to a new case, were analyzed. On the basis of the proofs provided for third ventricle intactness, a new topographical classification for IVC was developed, distinguishing between: (i) strict IVC, with a proved third ventricle floor integrity and (ii) non-strict IVC, without any reliable proof confirming the intactness of the third ventricle floor. Following this classification, clinical features, pathology and surgical outcome for strictly and non-strictly IVC were compared.Findings. For 105 IVC compiled, 36 belonged to the strictly group and 69 to the non-strictly group. Two pathological features were associated with the non-strictly IVC group: a preferentially adamantinomatous pattern (p=0.106) and wider and tighter adherences to third ventricle margins (p=0.01). The non-strict topography was also associated with a worse postoperative outcome (p=0.046). There was a significant relationship between the surgical approach and the final outcome (p=0.05), being the translamina terminalis approach associated with the best outcome.Conclusions. Two different topographies might be considered among IVC: strict and non-strict intraventricular location. Non-strictly IVC have wider and tighter adhesions to third ventricle boundaries and this subtype is associated with a worse outcome.

Infundibulo-tuberal or not strictly intraventricular craniopharyngioma: evidence for a major topographical category.

PurposeThis study investigates retrospectively the clinical, neuroradiological, pathological and surgical evidence verifying the infundibulo-tuberal topography for craniopharyngiomas (CPs). Infundibulo-tuberal CPs represent a surgical challenge due to their close anatomical relationships with the hypothalamus. An accurate definition of this topographical category is essential in order to prevent any undue injury to vital diencephalic centres.MethodsA systematic review of all scientific reports involving pathological, neuroradiological or surgical descriptions of either well-described individual cases or large series of CPs published in official journals and text books from 1892 to 2011 was carried out. A total of 1,232 documents providing pathological, surgical and/or neuroradiological evidence for the infundibulo-tuberal or hypothalamic location of CPs were finally analysed in this study.FindingsFor a total of 3,571 CPs included in 67 pathological, surgical or neuroradiological series, 1,494 CPs (42%) were classified as infundibulo-tuberal lesions. This topography was proved in the autopsy of 122 non-operated cases. The crucial morphological finding characterizing the tubero-infundibular topography was the replacement of the third ventricle floor by a lesion with a predominant intraventricular growth. This type of CP usually presents a circumferential band of tight adherence to the third ventricle floor remnants, formed by a functionless layer of rective gliosis of a variable thickness. After complete surgical removal of an infundibulo-tuberal CP, a wide defect or breach at the floor of the third ventricle is regularly observed both in the surgical field and on postoperative magnetic resonance imaging studies.ConclusionsInfundibulo-tuberal CPs represent a major topographical category of lesions with a primary subpial development at the floor of the third ventricle. These lesions expand within the hypothalamus itself and subsequently occupy the third ventricle; consequently, they can be classified as not strictly intraventricular CPs. A tight attachment to the hypothalamus and remnants of the third ventricle floor is the pathological landmark of infundibulo-tuberal CPs.

Predictive factors for craniopharyngioma recurrence: a systematic review and illustrative case report of a rapid recurrence.

BACKGROUND Recurrence of craniopharyngiomas (CPs) represents a frequent and unpredictable incident. Rapid tumor recurrence within a few months after surgery has been rarely reported. Nondefinitive predictive factors for rapid CP recurrence have been identified to date. We have systematically analyzed the tumor factors that presumably influence in CP recurrence. METHODS We present the histologic and immunohistochemical analysis of an infundibulo-tuberal CP that was operated twice within a 3-month interval due to rapid recurrence. We investigated the differential characteristics of the subgroup of CPs that recurred in large surgical series published in the literature, along with cases reporting rapid tumor recurrence after surgery. RESULTS Specimens of our patient showed an adamantinomatous CP with whorl-like arrays and thick peritumoral gliosis. Ki-67 labeling index in primary and recurrent samples was 20% and 15%, respectively. p53 labeling index was 18% and 15%, respectively. The thorough analysis of literature showed that presence of tumor remnants and missing radiotherapy treatment after subtotal removal are strong predictors of tumor recurrence. Third ventricle involvement, large tumor size, tight adherence to surrounding structures, and presence of whorl-like arrays might also foster recurrence. High Ki-67 levels, p53 expression, and an intense reactive gliosis might point to rapid tumor growth. CONCLUSIONS Reliable tumor markers that predict CP recurrence are still lacking. The CP features presumably related to a higher risk of its recurrence are thought to be a larger tumor size, a tight adherence to the hypothalamus, the presence of whorl-like arrays, and high Ki-67 and p53 levels.

Displacement of mammillary bodies by craniopharyngiomas involving the third ventricle: surgical-MRI correlation and use in topographical diagnosis

OBJECT Accurate diagnosis of the topographical relationships of craniopharyngiomas (CPs) involving the third ventricle and/or hypothalamus remains a challenging issue that critically influences the prediction of risks associated with their radical surgical removal. This study evaluates the diagnostic accuracy of MRI to define the precise topographical relationships between intraventricular CPs, the third ventricle, and the hypothalamus. METHODS An extensive retrospective review of well-described CPs reported in the MRI era between 1990 and 2009 yielded 875 lesions largely or wholly involving the third ventricle. Craniopharyngiomas with midsagittal and coronal preoperative and postoperative MRI studies, in addition to detailed descriptions of clinical and surgical findings, were selected from this database (n = 130). The position of the CP and the morphological distortions caused by the tumor on the sella turcica, suprasellar cistern, optic chiasm, pituitary stalk, and third ventricle floor, including the infundibulum, tuber cinereum, and mammillary bodies (MBs), were analyzed on both preoperative and postoperative MRI studies. These changes were correlated with the definitive CP topography and type of third ventricle involvement by the lesion, as confirmed surgically. RESULTS The mammillary body angle (MBA) is the angle formed by the intersection of a plane tangential to the base of the MBs and a plane parallel to the floor of the fourth ventricle in midsagittal MRI studies. Measurement of the MBA represented a reliable neuroradiological sign that could be used to discriminate the type of intraventricular involvement by the CP in 83% of cases in this series (n = 109). An acute MBA (< 60°) was indicative of a primary tuberal-intraventricular topography, whereas an obtuse MBA (> 90°) denoted a primary suprasellar CP position, causing either an invagination of the third ventricle (pseudointraventricular lesion) or its invasion (secondarily intraventricular lesion; p < 0.01). A multivariate model including a combination of 5 variables (the MBA, position of the hypothalamus, presence of hydrocephalus, psychiatric symptoms, and patient age) allowed an accurate definition of the CP topography preoperatively in 74%-90% of lesions, depending on the specific type of relationship between the tumor and third ventricle. CONCLUSIONS The type of mammillary body displacement caused by CPs represents a valuable clue for ascertaining the topographical relationships between these lesions and the third ventricle on preoperative MRI studies. The MBA provides a useful sign to preoperatively differentiate a primary intraventricular CP originating at the infundibulotuberal area from a primary suprasellar CP, which either invaginated or secondarily invaded the third ventricle.

Recovery from paraplegia after the treatment of spinal dural arteriovenous fistula: case report and review of the literature

BackgroundSpinal dural arteriovenous fistula (SDAVF) is a rare and enigmatic disease. Functional outcome is particularly uncertain for the small group of patients that are unable to stand at the time of diagnosis (grade 5 gait disturbance on the Aminoff-Logue scale, ALS). The objective of this study is to examine the final functional outcome of patients with SDAVF in grade 5 gait ALS before treatment.MethodsWe conducted a PubMed search using the keyword “spinal dural arteriovenous fistula.” A review of the clinical series and single well-detailed case reports of SDAVF gathered 106 patients with grade 5 gait ALS on the initial examination. Additionally, we report the case of a 56-year-old man presenting acute paraplegia and urinary retention on admission who had complained of sporadic motor and sphincter disturbances for 1 year. Spine T2-weighted MR imaging showed a central hyperintensity within the spinal cord, and the angiography demonstrated a T-11 SDAVF. Interruption of the fistula was performed through an urgent one-level laminectomy.ResultsGrade 5 gait ALS was present in 25% of the patients with SDAVF included in the clinical series. Latest follow-up showed that gait disturbance improved in 73% of patients after treatment, although less than 6% became grade 1 gait ALS. Micturition disturbances improved in 39%. Exploration of our patient showed improvement to grade 1 gait ALS 1 year after the surgical treatment.ConclusionInterruption of SDAVF in paraplegic patients may improve the final functional gait outcome in some cases. No complete recovery (grade 0 gait ALS) was achieved after treatment. Micturition disturbances had a worse prognosis than motor deficits.

Craniopharyngiomas with a mixed histological pattern: the missing link to the intriguing pathogenesis of adamantinomatous and squamous-papillary varieties?

We read with great interest the manuscript by Okada et al. reporting the coexistence of adamantinomatous and squamous-papillary elements on a large intraventricular craniopharyngioma (CP). First and foremost, we would like to point out the importance of this case because it provides compelling evidence against the classic sharp histological classification into adamantinomatous and papillary CP variants.With the present letter, we want to discuss some additional topographical, histological and molecular evidence, which supports the differentiation of a mixed CP variety and may contribute to a better understanding of CP pathogenesis. CP is one of the most intriguing histopathological entities. Several important questions regarding CP’s origin and histological classification have remained unsolved since the first definition of this tumor by the German pathologist Jacob Erdheim in 1904. A major source of confusion is due to the high variability regarding the patient’s age at presentation, topographical extension, morphological configuration and biological behavior among CPs. Some thorough pathologic investigations on CPs, published long ago, remarked on the considerable degree of variation in the growth patterns of these epithelial tumors. However, the World Health Organization has kept in force the traditional classification into two major pathological variants, adamantinomatous CP (aCP) and squamous-papillary CP (pCP), within the latest classification of brain tumors. The epithelium of aCP resembles to that of the enamel organ or the calcifying odontogenic cysts of the jaw. In contrast, the epithelium of pCP which is compact and presents papillary projections within the surrounding tissues, resembles the structure of the oral mucosa. Several authors have presented evidence against such a rigid classification into aCPs and pCPs. Carol K. Petito was one of the first pathologists who questioned the validity of this distinction, after observing in her series of 245 CPs a high rate of lesions (approximately 33%) presenting a mixture of both variants. In the following decades, the existence of mixed or transitional forms between the papillary and adamantinomatous types was confirmed in both large series and well-described individual cases. In the series of 131 CPs reviewed by Szeifert et al. 38% of the cases belonged to the adamantinomatous group, 26% corresponded to the squamous epithelial type and 15% of the cases corresponded to a mixed variant combining features from both types. In the series of 56 patients studied by Miller et al. three cases showed a mixed histological pattern, one in a child and two in adults. Crotty et al. also reported four cases of mixed CPs in his seminal review of the squamous-papillary type, three of these cases exhibited alternating areas with definite adamantinomatous and papillary-squamous differentiation while in the fourth lesion the epithelium displayed an intermingled appearance. To the best of our knowledge, at least another three well-described cases of mixed CPs have been published to date; interestingly, all of them were developed within the third ventricle and were diagnosed in adult patients. On the basis of the previous body of evidence, the mixed CP type should not be considered as a rarity, but rather as a definite variant showing overlapping histological features from the aCP and pCP varieties. A proper recognition of mixed CPs is important not only for academic reasons, but also may give additional insights into the uncertain pathogenesis of CPs. The definition of two distinct histological CP variants and the preferential association of each one to a specific age group has favored the proposal of two main hypotheses concerning the origins of these lesions. The “embryogenetic theory” states that adamantinomatous CPs, mostly found in children, originate from epithelial remnants of the Ratkhe’s pouch/craniopharyngeal duct left over during embryogenesis of the pituitary gland which would have had a neoplastic transformation. On the other hand, the “metaplastic theory” was formulated for squamouspapillary lesions, usually found in adults, which suggests that they originate from metaplasia of adenohypophyseal cells within the pituitary gland. Nevertheless, the available evidence cannot give any separate explanation about Correspondence: Ruth Prieto, MD, PhD, Department of Neurosurgery, Virgen de La Salud Hospital, Av. Barber 30, CP 45004 Toledo, Spain. Email: rprieto29@hotmail.com Published online 27 March 2013. bs_bs_banner

Acute hemorrhage in a colloid cyst of the third ventricle: A rare cause of sudden deterioration.

Background: Acute neurological deterioration and death in a patient harboring a colloid cyst of the third ventricle remains a poorly understood phenomenon. Sudden neurological derangement caused by spontaneous bleeding within a colloid cyst is a rare and potentially fatal event, usually requiring immediate diagnosis and emergency surgical treatment. Case Description: A 47-year-old male presented with acute right-sided hemiparesis and speech impediment, followed by rapid deterioration of consciousness. Neuroimaging studies showed a rounded mass at the roof of the anterior third ventricle, causing biventricular hydrocephalus along with a left-sided basal ganglia hematoma. The lesion showed scattered foci of a recent hemorrhage which extended into the left lateral ventricle. Surgical treatment involved emergency external ventricular drainage followed by the prompt elective total resection of the lesion via a transcallosal route. Pathological findings confirmed the diagnosis of a colloid cyst with focal areas of vascular congestion and blood extravasation within its wall. Conclusions: Spontaneous bleeding into a colloid cyst of the third ventricle may cause acute obstructive hydrocephalus and intracranial hypertension due to rapid enlargement of the lesion. This event may account for the sudden neurological deterioration and/or death observed in a previously asymptomatic patient. The diagnosis of hemorrhagic phenomena within a colloid cyst represents a challenge due to the variable signal usually displayed by these lesions on computed tomography (CT) and magnetic resonance imaging (MRI). Emergency ventricular drainage followed by elective tumoral removal constitutes a valid and safe treatment strategy.

Low-grade malignant triton tumor in the lumbar spine: A rare variant of malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation

Malignant peripheral nerve sheath tumor (MPNST) is an uncommon type of sarcoma that arises from peripheral nerve sheaths and rarely involves the spinal roots. The origin of this tumor is thought to be Schwann cells or pluripotent cells of the neural crest. The subgroup of tumors in which malignant Schwann cells coexist with malignant rhabdomyoblasts is termed malignant triton tumor (MTT). MPNSTs can show different degrees of malignancy, but overall spinal MTTs are high‐grade lesions. We report the exceptional instance of a spinal low‐grade MTT in a 39‐year‐old man treated with total surgical removal followed by local radiation therapy. Histological low grade was based on the lack of necrosis, a low grade of atypia, a low mitotic rate and a Ki‐67 labelling index <25%. After 18 months of follow‐up the patient is alive with no evidence of disease. A thorough review of the literature yielded 57 well‐documented spinal MPNSTs. Ten of them corresponded to MTTs, but none showed low‐grade features. An analysis of the clinical, radiological and treatment data was performed to identify factors that might influence the outcome. Overall the 18‐month survival rate was 45% but dropped to 0% in the subgroup of spinal MTTs. Besides, a size exceeding 2 cm, extra‐spinal extension, association with neurofibromatosis and subtotal removal were all related to a worse outcome. In conclusion, spinal MTTs generally exhibit a more aggressive behavior than conventional MPNSTs. The occurrence of a spinal low‐grade MTT with a better prognosis should also be recognized.

Chordoid glioma of the third ventricle attached to the optic chiasm: Successful removal through a trans-lamina terminalis approach

Chordoid glioma of the third ventricle constitutes a rare, very recently recognized histological entity. Most reports of this neoplasm, focused on its distinct histological features, have hypothesized about a probable origin of the lesion at the third ventricle floor and/or the lamina terminalis. We report on a new case, presenting neuroradiological and intraoperative pictorial evidences of the tumoral attachment, limited to the chiasm-lamina terminalis junction. A 53-year-old woman debuted with acute symptoms of obstructive hydrocephalus, visual disturbances and confusion. MRI investigation showed a large solid-cystic third ventricle mass bulging through the lamina terminalis and ventricular floor. After placing a ventriculoperitoneal shunt, the tumor was completely removed through a trans-lamina terminalis approach. A tight tumoral attachment to the junction of the posterior chiasm to the lamina terminalis was identified and dissected. No other adhesions to the third ventricle boundaries were found. A chordoid glioma was diagnosed on histological examination. One year after the surgical procedure the patient does not present new neurological deficits, and there are no signs of tumoral regrowth on the follow-up postoperative MRI. Chordoid glioma should be included in the differential diagnosis of third ventricle tumors. Preoperative neuroradiological suspicion of this lesion should alert the neurosurgeon about the presence of a tight tumoral adherence at the level of the chiasm-lamina terminalis junction. The trans-lamina terminalis approach provides a suitable route for an early control of this attachment under direct vision, allowing a safe dissection of the mass from the third ventricle.