Natural history and neuro-oncological approach in spinal gangliogliomas: a systematic review.

To describe the natural history of spinal gangliogliomas (GG) in order to determine the most appropriate neuro-oncological management. A Medline search for relevant publications up to July 2023 using the key phrase "ganglioglioma spinal" and "ganglioglioma posterior fossa" led to the retrieval of 178 studies. This corpus provided the basis for the present review. As an initial selection step, the following inclusion criteria were adopted: (i) series and case reports on spinal GG; (ii) clinical outcomes were reported specifically for GG; (iii) GG was the only pathological diagnosis for the evaluation of the tumor; (iv) papers written only in English was evaluated; and (v) papers describing each case in the series were included. The World Health Organization (WHO) 2021 grading criteria for gangliogliomas were applied. A total of 107 tumors were evaluated (63 from male patients and 44 from female patients; 1.43 male/1.0 female ratio, mean age 18.34 ± 15.84 years). The most common site was the cervical spine, accounting for 43 cases (40.18%); GTR was performed in 35 cases (32.71%) and STR in 71 cases (66.35%), while this information was not reported in 1 case (0.94%). 8 deaths were reported (7.47%) involving 2 males (25%) and 6 females (75%) aged 4-78 years (mean 34.27 ± 18.22) years. GGs located on the spine displayed the same gender ratio as these tumors in general. The most frequent symptom was pain and motor impairment, while the most prevalent location was the cervical spinal cord. GTR of the tumor posed a challenge for neurosurgeons, due to the difficulty of resecting the lesion without damaging the spinal eloquent area, explaining the lower rate of cure for this tumor type.

Impact of a cell cycle and an extracellular matrix remodeling transcriptional signature on tumor progression and correlation with EZH2 expression in meningioma.

OBJECTIVE: The authors searched for genetic and transcriptional signatures associated with tumor progression and recurrence in their cohort of patients with meningiomas, combining the analysis of targeted exome, NF2-LOH, transcriptome, and protein expressions. METHODS: The authors included 91 patients who underwent resection of intracranial meningioma at their institution between June 2000 and November 2007. The search of somatic mutations was performed by Next Generation Sequencing through a customized panel and multiplex ligation-dependent probe amplification for NF2 loss of heterozygosity. The transcriptomic profile was analyzed by QuantSeq 3' mRNA-Seq. The differentially expressed genes of interest were validated at the protein level analysis by immunohistochemistry. RESULTS: The transcriptomic analysis identified an upregulated set of genes related to metabolism and cell cycle and downregulated genes related to immune response and extracellular matrix remodeling in grade 2 (atypical) meningiomas, with a significant difference in recurrent compared with nonrecurrent cases. EZH2 nuclear positivity associated with grade 2, particularly with recurrent tumors and EZH2 gene expression level, correlated positively with the expression of genes related to cell cycle and negatively to genes related to immune response and regulation of cell motility. CONCLUSIONS: The authors identified modules of dysregulated genes in grade 2 meningiomas related to the activation of oxidative metabolism, cell division, cell motility due to extracellular remodeling, and immune evasion that were predictive of survival and exhibited significant correlations with EZH2 expression.

Assessment of hemorrhagic onset on meningiomas: Systematic review.

OBJECTIVE: To review the data published on the subject to create a more comprehensive natural history of the haemorrhagic onset of meningiomas (IVMs). PATIENTS AND METHODS: A Medline search up to June 2020, using the search term "bleeding meningioma," returned 136 papers. As a first selection step, we adopted the following inclusion criteria: series and case reports about bleeding meningioma. Papers written in other languages but with abstracts written in English were also evaluated. RESULTS: A total of 190 tumours were evaluated, specifically 109 tumours from female patients and 81 tumours from male patients with a ratio of 1.34 female to 1.0 male (mean age of 54.86 ± 16.1years old). The majority were located in the convexity (129-67.9 %). Among the 190 tumours evaluated, 171 patients (90 %) presented with GI tumours, with a predominance of the meningothelial subtype (32.6 %). Nine patients (4.7 %) presented with grade GII tumours, and 10 (5.3 %) presented with GIII tumours. The most prevalent type was intracerebral haemorrhage (ICH) at 50 %, followed by subdural at 27.36 %; the mortality rate was 13.1 % (25 deaths), the distribution of both location (prevalence of convexity: 18-72 %) and histopathology (grade 1: 22-88 %). CONCLUSION: These tumours follow the histopathological distribution of meningiomas, in general. The age distribution shows prevalence among the adult population but with a greater proportion in the elderly. The fact that the overwhelming majority of cases involve meningiomas with a benign histological subtype is noteworthy. Another relevant factor observed is that most reports are from Asian origin.

Cyclin E1 expression and malignancy in meningiomas.

OBJECTIVE: The aim of the present study was to analyze if the pathway Skp2-p27-cyclin E1 could also be a tumor progression marker for meningiomas. PATIENTS AND METHODS: We used quantitative real-time PCR to assess the relative expression levels of the genes coding for cyclin E1 (CCNE1), Skp2 (SKP2), and p27 (P27). The expression levels were compared in grades I to III meningiomas and among different histological subtypes of grade I meningiomas. RESULTS: Anaplastic meningiomas accounted for 4.9%, atypical meningiomas for 23.5% and grade I meningiomas for 71.6%.CCNE1 expression level was significantly higher in grade II compared to grade I meningiomas (p = 0.0027), and its expression level reliably predicts grade II meningiomas (ROC AUC = 0.731, p = 0.003). CCNE1 expression also correlated with SKP2 and P27 expression levels in grade I meningiomas (r = 0.539, p < 0.0001 and r = 0.687, p = <0.0001, respectively for CCNE1/SKP2 and CCNE1/P27, Spearman's test). Fibrous subtype among grade I meningiomas presented the highest expression levels of CCNE1, SKP2 and P27. Higher expression of cyclin E1 protein was detected in the nuclei of atypical meningiomas compared to grade I meningiomas. CONCLUSIONS: CCNE1 expression level predicts meningioma malignancy, and the fibrous subtype presents the highest gene expression levels among grade I meningiomas.

Natural history of intraventricular meningiomas: systematic review.

Review the data published on the subject to create a more comprehensive natural history of intraventricular meningiomas (IVMs). A Medline search up to March 2018 using "intraventricular meningioma" returned 98 papers. As a first selection step, we adopted the following inclusion criteria: series and case reports about IVMs, as well as papers written in other languages, but abstracts written in English were evaluated. Six hundred eighty-one tumors were evaluated from 98 papers. The majority of the tumors were located in the lateral ventricles (602-88.4%), fourth ventricle (59-8.7%), and third ventricle (20-2.9%). These tumors accounted for a mortality rate of 4.0% (25 deaths) and a recurrence rate of 5.3% (26 recurrences). The majority of the tumors were grade I (89.8%) and consisted of the following subtypes: fibrous, 39.7% (n = 171); transitional, 22.0% (n = 95); meningothelial, 18.6% (n = 80); angiomatosus, 3.2% (n = 14); psammomatous, 2.6% (n = 11); and others, 13.9% (n = 60). Forty-five patients (7.4%) presented with grade II (GII) tumors, and 17 patients (2.8%) presented with grade III (GIII) tumors. These tumors follow the histopathological distribution of meningiomas in general, with the exception of the higher prevalence of the fibrous subtype, possibly due to its embryonic origin. Recurrence and mortality were lower than in other localizations likely due to a complete surgical resection rate than in the convexity and skull base, which suggests that GTR is the gold standard for the management of IVMs.

Molecular alterations in meningiomas: Literature review.

Meningiomas, tumors that originate from meningothelial cells, account for approximately 30% of all new diagnoses of central nervous system neoplasms. According to the 2016 WHO classification of central nervous system tumors meningiomas are classified into three grades: I, II, and III. Past studies have shown that the risk of meningiomas recurrence is strongly correlated with the molecular profile of the tumor. Extensive whole-exome or whole-genome sequencing has provided a large body of information about the mutational landscape of meningiomas. However, such a stratification of meningiomas based on mutational analysis alone has been proven not to satisfy the clinical need for distinction between patients who need (or do not need) an adjuvant treatment. Combined analysis of exome, transcriptome, methylome and future approaches for epigenetic aspects in meningiomas may allow researchers to unveil a more comprehensive understanding of tumor progression mechanisms and, consequently, a more personalized clinical approach for patients with meningioma. A better understanding of the genetics and clinical behavior of high-grade meningiomas is mandatory in order to better design future clinical trials. By studying the mechanisms underlying these new tumorigenesis pathways, we should be able to offer personalized chemotherapy to patients with surgery and radiation-refractory meningiomas in the near future. The purpose of this article is to accurately bring the compilation of this information, for a greater understanding of the subject.

Impact of radiotherapy in atypical meningioma recurrence: literature review.

Evaluate whether radiotherapy (RT) after the neurosurgical treatment of atypical meningiomas (AM) has an impact on the reduction rate of recurrence. A Medline search through October 2017 using "atypical meningioma" returned 1277 papers for initial review. Inclusion criteria were as follows. We analyzed the database and included articles in which the anatomic pathological classification of atypical meningiomas was in accordance with WHO 2007 or WHO 2016 criteria, patients > 18 years of age, and there was postoperative external beam radiation to the tumor bed. Exclusion criteria were WHO grade I or III meningioma, patients who underwent whole-brain radiation, RT used as salvage therapy for recurrence, palliative dose of RT (< 45 Gy), recurrent AMs, and multiple AMs. Papers reporting outcomes in which atypical and anaplastic meningiomas were analyzed together were rejected, as were papers with small samples that may compromise evaluation. After filtering our initial selection, only 17 papers were selected. After reviewing the seventeen articles including a total of 1761 patients (972 female and 799 male; 1.21 female/1.0 male), the difference in proportion of tumor recurrence between patients with and without radiotherapy after neurosurgical procedure was 1.0448, 95% CI [0.8318 to 1.3125], p value = 0.7062. On the basis of this review, there is no evidence to suggest that RT decreases the rate of recurrence in patients with atypical meningiomas.

Atypical and Malignant Meningiomas: Neurooncologic Management in a Brazilian cohort.

OBJECTIVE: To analyze the surgical and oncologic treatment of a Brazilian cohort of patients with grade II and III meningioma at a follow-up time of 15 years to get an overview of these patients' outcomes. METHODS: Cross-sectional study of 43 patients (26 women, 17 men; age range 20 to 83 years; average 57.72 ± 14.54) operated on from 2000 to 2014 at a single institution, with the neuropathologic diagnosis of meningioma grade II (39 patients) and grade III (4 patients). RESULTS: Radiotherapy: 24 patients (55.81%) underwent radiotherapy; the time between the surgical procedure and the beginning of radiotherapy was 5 months; 7 patients with a diagnosis of AM underwent a new surgical procedure, albeit of adjuvant therapy, because of tumor recurrence, and only 3 of them underwent radiotherapy after the first resection. Mortality: in total, 19 deaths (44.18%) were identified in this sample: 15 (38.46%) with GII and 4 (100%) with GIII. The 10-year survival was expected in 35% of GII patients and 0% of GIII patients. CONCLUSION: Surgery is still the main form of treatment and the mainstay for prolonging survival. Radiotherapy is still controversial; however, we observed its positive impact on recurrence and progression-free survival.

Clinical Outcome, Tumor Recurrence, and Causes of Death: A Long-Term Follow-Up of Surgically Treated Meningiomas.

OBJECTIVE: The medical literature still lacks information about the impact of surgery and adjuvant treatment on the life of patients with meningioma. The clinical outcome, timing of tumor recurrence, and causes of death are often overlooked. This study evaluates these data taking into account tumor localization and histologic grade. METHODS: The article is a cross-sectional study of patients operated on between 2000 and 2014 in a single institution. The series has 593 adult patients (442 females and 151 males) and follow-up of 68.8 ± 48.9 months. Imaging of 434 patients was reviewed and 379 patients/families interviewed. RESULTS: Sixty-eight deaths were related to tumor treatment/progression and 36 to other causes. After 2 years of surgery, deaths not related to tumor were 7 times more frequent than were tumor-related deaths (odds ratio, 7.1; 95% confidence interval, 2.8-19.5; P < 0.0001). Ten-year survival was expected in 85% of patients with grade I (GI) meningioma, 35% of patients with atypic (GII) meningioma, and 0% of patients with anaplastic (GIII) meningioma. Convexity tumors had about half the risk of recurrence compared with other localizations (odds ratio, 0.4; 95% confidence interval, 0.27-0.67; P = 0.0002). In GI meningioma, recurrence was neither related to death nor to impairment of independent life. All patients with GII and GIII meningioma who had recurrence died. 96.3% of interviewees reported neurologic improvement or stability after the surgery. CONCLUSIONS: Histologic grade is the most important factor for long-term survival. Complete resection has to be pursued in GII and GIII meningioma but must be carefully weighed against morbidities in GI meningioma.

Predictors of Outcome in Nontraumatic Spontaneous Acute Spinal Subdural Hematoma: Case Report and Literature Review.

OBJECTIVES: To analyze the clinical presentation and outcome of nontraumatic spontaneous acute spinal subdural hematoma by observing the predictors of outcome. METHODS/RESULTS: This study was based on a case report and systematic review of the international literature. Among the 151 patients, 80 were female and 65 were male (1.25 female/1.0 male). The age distribution ranged from 6 months to 87 years, with a small increase in incidence between the first and second decade of life and a major peak at age 60 years. The difference of proportion of good results between patients with and without established neurologic deficits was: 0.488, 95% confidence interval (95% CI) 0.237-0.648, P = 2.71e-08; coagulopathy was 0.335, 95% CI 0.163-0.508, P = 0.0002; SAH was 0.0539, 95% CI -0.119 to 0.226, P = 0.6529; lumbar puncture/associated diseases was 0.149 95% CI -0.032 to 0.330, P = 0.1171; surgery was 0.0593, 95% CI -0.114 to 0.233, P = 0.5838; and hematoma extension equal or longer than 5 levels was 0.010 95% CI -0.178 to 0.197, P = 1. CONCLUSIONS: Although mortality and morbidity associated with nontraumatic spontaneous acute spinal subdural hematoma has decreased during the last 2 decades, the disease still carries a mortality rate of approximately1.3% and a morbidity (permanent neurologic deficits) rate of 28%. The main factors affecting the outcome are neurologic status at presentation and coagulopathies.

Sensory abnormalities and masticatory function after microvascular decompression or balloon compression for trigeminal neuralgia compared with carbamazepine and healthy controls.

OBJECT: Idiopathic trigeminal neuralgia (iTN) is a neurological condition treated with pharmacotherapy or neurosurgery. There is a lack of comparative papers regarding the outcomes of neurosurgery in patients with iTN. The objective of this study was to investigate sensory thresholds and masticatory function in 78 patients with iTN who underwent microvascular decompression (MVD) or balloon compression (BC), and compare these treatments with carbamazepine and 30 untreated healthy controls. METHODS: The authors conducted a case-controlled longitudinal study. Patients were referred to 1 of 3 groups: MVD, BC, or carbamazepine. All patients were evaluated before and after treatment with a systematic protocol composed of a clinical orofacial questionnaire, Research Diagnostic Criteria for temporomandibular disorders, Helkimo indices, and a quantitative sensory-testing protocol (gustative, olfactory, cold, warm, touch, vibration, superficial, and deep pain thresholds). RESULTS: Both MVD and BC were effective at reducing pain intensity (p = 0.012) and carbamazepine doses (p < 0.001). Myofascial and articular complaints decreased in both groups (p < 0.001), but only the patients in the MVD group showed improvement in Helkimo indices (p < 0.003). Patients who underwent MVD also showed an increase in sweet (p = 0.014) and salty (p = 0.003) thresholds. The sour threshold decreased (p = 0.003) and cold and warm thresholds increased (p < 0.001) in patients after MVD and BC, but only the patients who underwent BC had an increase in touch threshold (p < 0.001). CONCLUSIONS: Microvascular decompression and BC resulted in a reduction in myofascial and jaw articular complaints, and the impact on masticatory function according to Helkimo indices was greater after BC than MVD. MVD resulted in more gustative alterations, and both procedures caused impairment in thermal thresholds (warm and cold). However, only BC also affected touch perception. The sensorial and motor deficits after BC need to be included as targets directly associated with the success of the surgery and need to be assessed and relieved as goals in the treatment of iTN.

Models of functional cerebral localization at the dawning of modern neurosurgery.

The concept of a functional cerebral localization gave the needed support for the development of neurosurgery as a specialty. It should be noted though that the presence of functions on discrete areas of the cortex was a very controversial topic at that time. The objective of this paper is to review models of cortical organization at the end of the 19th century, highlighting beliefs, theories, and controversies behind them. A better understanding of this historical moment is essential to appreciate the debate between holists and localizers that stirred neuroscientists worldwide in the first half of the 20th century.

Microsurgical treatment of tentorial meningiomas: Report of 30 patients.

BACKGROUND: Tentorial meningiomas represent about 5% of intracranial meningiomas. This article reviews our recent institutional series of patients with tentorial meningiomas, proposes a simplified classification and analyzes postoperative evolution, discussing the salient features in the management of these patients. METHODS: From 1998 to 2005, 30 patients (22 female and 8 male) with tentorial meningiomas were operated at our institution. Thirteen patients had tumor restricted to the infratentorial space; 12, to the supratentorial space; and in 5 cases, the tumor involved both compartments. Follow-up ranged from 1 to 8 years. A total of 35 surgical procedures were performed in 30 patients, where 26 procedures were performed through a single approach (2, ITSC; 10, RS; 5, SOIH; 5, ST; and 4, TT); and 9, through combined approaches (7, ITSC/ SOIH; and 2, RS/ST). RESULTS: Simpson I resection was achieved in 17 patients. Tumors involving both compartments, involving the petrous sinus, and attached to the torcula limited complete resection. Twenty-two out of 30 patients were able to return to their regular life with no or minimal neurological sequelae. Most frequent complications in our series were shunt dependence, CSF fistulae, diffuse brain injury and visual field defects. Overall, our series revealed 3% mortality and 23% morbidity. CONCLUSION: Tentorial meningiomas are associated with significant morbidity related to the nervous and vascular structures surrounding the tumor. Partial tumor removal may be necessary in some cases.

Epilepsy surgery: historical highlights 1909-2009.

This review focuses on some historical highlights of the surgery of epilepsy, beginning with the reports of Horsley, Krause, and Cushing to which appeared in 1909, the year that The International League Against Epilepsy (ILAE) was inaugurated. We then outline key contributions from Europe and North America, and examine particularly the evolution of our understanding of temporal lobe seizures, which have now become the most common form of epilepsy amenable to surgical cure.

Stereotactic disconnection of hypothalamic hamartoma to control seizure and behavior disturbance: case report and literature review.

An 18-year-old boy with refractory epilepsy and aggressiveness associated to a hypothalamic hamartoma was submitted to a stereotactically guided lesion by thermocoagulation. The target was based on magnetic resonance (MR) images merged with computed tomography scan images taken on the day of surgery while patient was on a stereotactic frame. In order to reveal structures not discernible in MR images, the Schaltenbrand digital brain atlas was merged onto the patient's images. Target and trajectory of the depth electrode were chosen based on three-dimensional imaging reconstructions. A surgical plan was devised to disconnect the hypothalamic hamartoma from the hypothalamus, medial forebrain bundle, fasciculus princeps, and dorsal longitudinal fasciculus. Our target was placed at the inferior portion of the posterolateral component of the hamartoma, bordering the normal hypothalamus. The patient evolved with marked lessening of aggressiveness. Seizure frequency was reduced from several seizures per day to less than one tonic-clonic seizure during sleep per month and only two episodes suggestive of partial complex seizures during daytime. These results have remained consistent over a 24-month postoperative follow-up. Functional neuroanatomy of hypothalamic connections involved in seizure propagation and aggressive behavior was reviewed.

From lateral to mesial: the quest for a surgical cure for temporal lobe epilepsy.

PURPOSE: A gap of more than a hundred years occurred between the first accounts of mesial temporal sclerosis and recognition of its role in the pathogenesis of psychomotor seizures. This paper reviews how the understanding and surgical treatment of temporal lobe epilepsy developed, particularly from the work of Penfield, Jasper, and their associates at the Montreal Neurological Institute (MNI). METHODS: Publications on EEG and surgery for temporal lobe seizures from 1935 to 1953 were reviewed and charts of selected patients operated on at the MNI in the same period were examined. Attention was focused on the evolution of surgical techniques for temporal lobe epilepsy. RESULTS: In the late 1930s, some EEG findings suggested deep-lying disturbances originating in the temporal lobe. However, it took another two decades before the correlation of clinical, neurophysiological, and anatomical findings provided evidence for the involvement of the mesial structures in psychomotor or temporal lobe seizures. From 1949 and onward, Penfield and his associates applied this evidence to extend the surgical resections to include the uncus and the hippocampus. CONCLUSION: The collaborative work of a team led by Penfield and Jasper at the MNI helped to define the role of neurophysiological studies in epilepsy surgery. As a result, the importance of removing the mesial structures in order to obtain better seizure control in patients with temporal lobe epilepsy became firmly established.

Postoperative fever after hemispherectomy: the role of non-infectious factors.

Postoperative fever is a usual source of concern among caregivers and patients' family given that it may reflect a wide range of complications. The objective of this paper was to outline the expected postoperative temperature variation after hemispherectomies, and to establish factors that affect this curve. From 1987 to 2003, 30 patients were hemispherectomized in our institution. Among them, 24 patients without clinical diagnosis of infection were selected for this study. Postoperative axillary temperature from each patient was recorded over 10 days. Data was initially analyzed for all 24 patients and, later, for subgroups by (1) surgical technique (functional hemispherectomy, anatomical hemispherectomy, and hemispherotomy) and (2) hemispheric volume of the causative pathology (groups with large, moderately atrophic, and severely atrophic hemispheres). There was a trend of temperature elevation (p=0.06) over the first 4 days in all patients where 14 subjects recorded values over 38.5 degrees C, and 3 over 39.0 degrees C. Temperature curves from subgroups undergoing different techniques presented no statistical differences. However, the group including causative pathologies with larger hemispheres had a higher temperature curve when compared to patients with severely atrophic hemispheres (p<0.05). Our findings support the view that fever is an predictable event after hemispherectomies and causative pathologies with larger hemispheres present higher postoperative temperatures.

Efficacy of and morbidity associated with stereoelectroencephalography using computerized tomography--or magnetic resonance imaging-guided electrode implantation.

OBJECT: The purpose of this paper was to define the general efficacy of and morbidity associated with stereoelectroencephalography using modem methods of imaging and to particularize the risks related to specific lobes of the brain. METHODS: All patients admitted to the Montreal Neurological Institute who had undergone either computerized tomography- or magnetic resonance imaging-guided electrode implantation by one surgeon (A.O.) were reviewed. The procedure was considered efficient if the obtained information was sufficient to make a decision either in support of or against surgery. Two hundred seventeen patients underwent 224 implantations with 3022 electrodes. Complications related to each lobe were as follows: temporal lobe, two abscesses (0.54%); frontal lobe, one abscess and three hematomas (1.4%); and occipital lobe, one hypointense lesion found 1 week after electrode explantation (2.6%). Significant risk factors associated with hematomas were implantation in the frontal lobe (p < 0.05) and the use of four or more implanted electrodes (p < 0.025). General complications included the following: 26 patients, psychiatric symptoms during monitoring; one patient, meningitis; four patients, scalp cellulitis; and two patients, hemiparesis during angiography in the early 1980s. One of these latter patients maintained a mild hemiparesis and represents the only case of permanent neurological sequela in the entire series. Data obtained during recordings supported an indication for surgery in 178 patients (79.5%), excluded a surgical option in 37 patients (16.5%), and were unsatisfactory in nine patients (4%). Thus, the overall efficacy as defined previously was 96%. CONCLUSIONS: Stereoelectroencephalography is an efficient procedure with low associated morbidity. Bilateral exploration of the temporal lobes has a morbidity rate of approximately 1%. A higher risk of hematomas occurs with the implantation of four or more electrodes in the frontal lobes.