Preoperative Immune-Inflammatory Status of the Patients With Newly-Diagnosed Glioblastoma - Could It Genuinely Predict Their Survival?

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive brain tumor affecting adult patients, with an extremely reduced overall survival despite rapid diagnosis and treatment. Therefore, it is crucial to establish accurate and affordable markers that allow an individualized approach to GBM patients. Serum biomarkers could be the most accessible, as complete blood counts should be performed on all GBM patients before undergoing any surgical and/or pharmacological treatment. However, their prognostic role is still unclear. Our study aims to assess the influence of various hematological markers of inflammation in predicting the outcome of GBM patients. MATERIAL AND METHODS: We retrospectively analyzed all adult patients diagnosed with primary glioblastoma in the Neurosurgery Department of the Emergency Clinical County Hospital of Târgu Mureș, Romania, from January 2017 until December 2019. We aimed to discover whether the immune/inflammatory status of the patients before receiving any kind of pharmacological or surgical treatment influenced their overall survival. RESULTS: Our study showed that pre-therapeutic elevated white blood count could predict reduced overall survival in not otherwise specified subtype (NOS) of GBMs (HR 0.4153, 95% CI 0.1825-0.9449, p 0.0362). Furthermore, patients with increased systemic immune response index (SIRI) had much larger tumors at the time of diagnosis (p 0.0359). In wild type, isocitrate dehydrogenase subpopulation (IDHwt), the higher values of neutrophil-to-lymphocyte ratio (NLR, p 0.0412), platelet-to-lymphocyte ratio (PLR, p 0.0376) and monocyte-to-lymphocyte ratio (MLR, p 0.0412) were related to more advanced age at the moment of diagnosis. Moreover, our results revealed a weakly positive association between tumor size and NLR values in the NOS group (Spearman r 0.3212, p 0.0493). CONCLUSIONS: Our study does not provide enough evidence for the immune/inflammatory status of GBM patients to be used as an efficient prognostic marker to guide the therapeutic approach.

The Role of Ketone Bodies in Treatment Individualization of Glioblastoma Patients.

Glioblastoma is the most common and aggressive primary brain tumor in adults. According to the 2021 WHO CNS, glioblastoma is assigned to the IDH wild-type classification, fulfilling the specific characteristic histopathology. We have conducted a prospective observational study to identify the glucose levels, ketone bodies, and the glucose-ketone index in three groups of subjects: two tumoral groups of patients with histopathological confirmation of glioblastoma (9 male patients, 7 female patients, mean age 55.6 years old) or grade 4 astrocytoma (4 male patients, 2 female patients, mean age 48.1 years old) and a control group (13 male patients, 9 female patients, mean age 53.9 years old) consisting of subjects with no personal pathological history. There were statistically significant differences between the mean values of glycemia (p value = 0.0003), ketones (p value = 0.0061), and glucose-ketone index (p value = 0.008) between the groups of patients. Mortality at 3 months in glioblastoma patients was 0% if the ketone levels were below 0.2 mM and 100% if ketones were over 0.5 mM. Patients with grade 4 astrocytoma and the control subjects all presented with ketone values of less than 0.2 mM and 0.0% mortality. In conclusion, highlighting new biomarkers which are more feasible to determine such as ketones or glucose-ketone index represents an essential step toward personalized medicine and survival prolongation in patients suffering from glioblastoma and grade 4 astrocytoma.

Ischemic Stroke in Patients with Cancer: a Retrospective Cross-Sectional Study.

INTRODUCTION: An increasing trend of cancer associated stroke has been noticed in the past decade. OBJECTIVES: To evaluate the risk factors and the incidence of neoplasia in stroke patients. MATERIAL AND METHOD: A retrospective, observational study was undertaken on 249 patients with stroke and active cancer (SAC) and 1563 patients with stroke without cancer (SWC). The general cardiovascular risk factors, the site of cancer, and the general clinical data were registered and evaluated. According to the "Oxfordshire Community Stroke Project" (OCSP) classification, all patients were classified into the clinical subtypes of stroke. The aetiology of stroke was considered as large-artery atherosclerosis, small vessel disease, cardio-embolic, cryptogenic or other determined cause. RESULTS: The severity of neurological deficits at admission were significantly higher in the SAC group (p<0.01). The haemoglobin level was significantly lower, and platelet level and erythrocyte sedimentation rate were significantly higher in the SAC group. Glycaemia, cholesterol and triglycerides levels were significantly higher in the SWC group. The personal history of hypertension was more frequent in the SWC group. In the SAC group, 28.9% had a cryptogenic aetiology, compared to 9.1% in SWC group. Cardio-embolic strokes were more frequent in the SAC group (24%) than the SWC group (19.6%). In the SAC group, 15,6% were diagnosed with cancer during the stroke hospitalization, and 78% of the SAC patients were without metastasis. CONCLUSIONS: The most frequent aetiologies of stroke in cancer patients were cryptogenic stroke, followed by large-artery atherosclerosis. SAC patients had more severe neurological deficits and worse clinical outcomes than SWC patients. Stroke in cancer patients appears to be more frequently cryptogenic, probably due to cancer associated thrombosis. The association between stroke and cancer is important, especially in stroke of cryptogenic mechanism, even in the presence of traditional cardiovascular risk factors.

Atypical posterior circulation strokes: a case-based review of rare anatomical variations involved.

The circle of Willis is a very important vascular mechanism of protecting against cerebral ischemia, especially when circulation within the main arteries irrigating the brain is somehow impeded. As result of congenital malformation arising early in embryonic development, the fetal-type posterior circle of Willis remains as such during the rest of one's life. Consequently, the posterior cerebral artery (PCA) becomes a branch of the internal carotid artery (ICA), rather than of the basilar artery (BA). Furthermore, the rest of collateral circulation, between the anterior and the posterior regions of the brain, is also negatively affected (e.g., leptomeningeal vessels). The anatomical variant represented by the artery of Percheron (AOP) has its origin on one of the PCAs, supplying singlehandedly both paramedian areas of the thalamus (right and left) and posterior regions of the midbrain. In the present study, we report a case of bilateral thalamic infarction with midbrain involvement, where the correct diagnosis was made retrospectively using computed tomography (CT) scan, magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI) and three-dimensional time-of-flight magnetic resonance angiography (3D TOF MRA).

An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain.

Background: Brain arteriovenous malformations (BAVMs) and cerebral cavernous malformations (CCMs) are rare developmental anomalies of the intracranial vasculature, with an irregular tendency to rupture, and as of yet incompletely deciphered pathophysiology. Because of their variety in location, morphology, and size, as well as unpredictable natural history, they represent a management challenge. MicroRNAs (miRNAs) are strands of non-coding RNA of around 20 nucleotides that are able to modulate the expression of target genes by binding completely or partially to their respective complementary sequences. Recent breakthroughs have been made on elucidating their contribution to BAVM and CCM occurrence, growth, and evolution; however, there are still countless gaps in our understanding of the mechanisms involved. Methods: We have searched the Medline (PubMed; PubMed Central) database for pertinent articles on miRNAs and their putative implications in BAVMs and CCMs. To this purpose, we employed various permutations of the terms and idioms: 'arteriovenous malformation', 'AVM', and 'BAVM', or 'cavernous malformation', 'cavernoma', and 'cavernous angioma' on the one hand; and 'microRNA', 'miRNA', and 'miR' on the other. Using cross-reference search; we then investigated additional articles concerning the individual miRNAs identified in other cerebral diseases. Results: Seven miRNAs were discovered to play a role in BAVMs, three of which were downregulated (miR-18a, miR-137, and miR-195*) and four upregulated (miR-7-5p, miR-199a-5p, miR-200b-3p, and let-7b-3p). Similarly, eight miRNAs were identified in CCM in humans and experimental animal models, two being upregulated (miR-27a and mmu-miR-3472a), and six downregulated (miR-125a, miR-361-5p, miR-370-3p, miR-181a-2-3p, miR-95-3p, and let-7b-3p). Conclusions: The following literature review endeavored to address the recent discoveries related to the various implications of miRNAs in the formation and growth of BAVMs and CCMs. Additionally, by presenting other cerebral pathologies correlated with these miRNAs, it aimed to emphasize the potential directions of upcoming research and biological therapies.

Effects of Surgery on the 30-Day Survival Rate in Spontaneous Supratentorial Intracerebral Hemorrhage.

Background: Spontaneous intracerebral hemorrhage (ICH) is a severe form of stroke. The efficacy of surgery as ICH treatment is controversial. We sought to compare the 30-day postoperative mortality rate between patients with surgically and medically treated ICH; Methods: This prospective study enrolled patients consecutively diagnosed with ICH and treated between 2017 and 2019. Patients meeting the study surgical indications were assigned to either surgical or medical treatment. The relationship between Glasgow Coma Scale (GCS) score, age, ICH location, ICH volume, and 30-day mortality was analyzed. Results: A total of 174 ICH patients were enrolled in this study. Of these, 136 met the surgery criteria; 65 of these underwent surgery (Group A), and 71 received medical treatment (Group B). Age and ICH location did not modify mortality. Although surgery did not overall improve mortality some better postsurgical outcomes were observed among patients surgically treated with GCS scores of at least 10 points and ICH volumes between 30 to 50 mL; Conclusions: Despite achieving an immediate reduction in intracranial pressure, surgery seems to be advantageous only for patients with ICH volumes between 30 to 50 mL and GCS scores of 10 points or higher.

Surgical Strategies and Clinical Outcome of Large to Giant Sphenoid Wing Meningiomas: A Case Series Study.

Large to giant sphenoid wing meningiomas (SWMs) remain surgically challenging due to frequent vascular encasement and a tendency for tumoral invasion of the cavernous sinus and optic canal. We aimed to study the quality of resection, postoperative clinical evolution, and recurrence rate of large SWMs. This retrospective study enrolled 21 patients who underwent surgery between January 2014 and December 2019 for SWMs > 5 cm in diameter (average 6.3 cm). Tumor association with cerebral edema, extension into the cavernous sinus or optic canal, degree of encasement of the major intracranial arteries, and tumor resection grade were recorded. Cognitive decline was the most common symptom (65% of patients), followed by visual decline (52%). Infiltration of the cavernous sinus and optical canal were identified in five and six patients, respectively. Varying degrees of arterial encasement were seen. Gross total resection was achieved in 67% of patients. Long-term follow-up revealed improvement in 17 patients (81%), deterioration in two patients (9.5%), and one death (4.7%) directly related to the surgical procedure. Seven patients displayed postoperative tumor progression and two required reintervention 3 years post initial surgery. Tumor size, vascular encasement, and skull base invasion mean that, despite technological advancements, surgical results are dependent on surgical strategy and skill. Appropriate microsurgical techniques can adequately solve arterial encasement but tumor progression remains an issue.

Fenestration of the cervical internal carotid artery misdiagnosed as dissection.

Internal carotid artery (ICA) anatomical variations are relatively rare occurrences during diagnostic imaging procedures. Their presence can have important prognostic consequences in the evaluation of vascular neurological diseases. It is therefore important to have a good knowledge about these variations, in order to avoid unwarranted medical interventions. We present the case of a patient harboring a right ICA fenestration in the cervical segment, misdiagnosed as a dissection on computed tomography angiography, admitted in the Department of Neurology and treated accordingly. The possible pathological and embryological origins of arterial fenestrations are discussed, and a brief review of the literature related to ICA fenestrations is presented.

First-Onset Hypokalemic Periodic Paralysis Following Surgery for Myxopapillary Ependymoma.

BACKGROUND: Hypokalemic periodic paralysis is a rare skeletal muscle channelopathy characterized by intermittent episodes of acute flaccid paralysis with associated hypokalemia. We present here the case of a first-onset hypokalemic periodic paralysis triggered by lumbar spinal surgery for tumor resection. CASE DESCRIPTION: A 37-year-old male without any known prior medical conditions presented with a first-onset attack of hypokalemic paralysis 1.5 days after lumbar spinal surgery for myxopapillary ependymoma. Initially, the patient presented paraparesis mimicking a spinal cord compression, and while en route for imaging there was an abrupt onset of flaccid paralysis with significant respiratory distress. The emergency blood tests revealed extreme hypokalemia with a serum potassium of 1.42 mm/L. The patient was transferred to the intensive care unit, intubated, sedated, and administered intravenous reperfusion with an infusion dose of 20 mEq/hour potassium in a solution of 5% mannitol. Following reperfusion, the patient recovered completely in 12 hours. Renal potassium hyperexcretion and hyperthyroidism were excluded by laboratory tests. The diagnosis was confirmed by genetic tests showing mutation of the CACNA1S gene. CONCLUSIONS: To the best of our knowledge, this is the first described case with the first onset triggered by a neurosurgical intervention and the second case following any kind of surgery. Neurosurgeons should consider hypokalemic periodic paralysis when encountering a rapidly evolving tetraparesis, even in an apparently healthy patient.

The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis.

Th17 cells, known as a highly pro-inflammatory subtype of Th cells, are involved very early in numerous aspects of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) neuropathology. A crucial event for the formation and accumulation of MS lesions is represented by the disruption of the blood brain barrier (BBB) in relapsing-remitting MS. Th17 cells also contribute to the progression of MS/EAE. These events will allow for the passage of inflammatory cells into the brain. Secondary to this, increased recruitment of neutrophils occurs, followed by increased protease activity that will continue to attract macrophages and monocytes, leading to brain inflammation with sustained myelin and axon damage. This review focuses mainly on the role of Th17 cells in penetrating the BBB and on their important effects on BBB disruption via their main secretion products, IL-17 and IL-22. We present the morphological aspects of Th17 cells that allow for intercellular contacts with BBB endothelial cells and the functional/secretory particularities of Th17 cells that allow for intercellular communications that enhance Th17 entry into the CNS. The cytokines and chemokines involved in these processes are described. In conclusion, Th17 cells can efficiently cross the BBB using pathways distinct from those used by Th1 cells, leading to BBB disruption, the activation of other inflammatory cells and neurodegeneration in MS patients.

Guillain-Barré and Acute Transverse Myelitis Overlap Syndrome Following Obstetric Surgery.

INTRODUCTION: There are rare reports of the occurrence of acute transverse myelitis and Guillain-Barré syndrome after various surgical procedures and general/epidural anaesthesia. The concomitant occurrence of these pathologies is very rare and is called Guillain-Barré and acute transverse myelitis overlap syndrome. In this article, we present the case of a second trimester pregnant patient who developed Guillain-Barré and acute transverse myelitis overlap syndrome. CASE PRESENTATION: We report the case of a 16-year-old female patient who underwent a therapeutic termination of pregnancy two weeks prior to the onset of the disease with gradual development of a motor deficit with walking and sensitivity disorders, fecal incontinence. The diagnosis was based on clinical exam, electroneurography and spinal magnetic resonance imaging. Endocrinopathies, infectious diseases, autoimmune and inflammatory diseases, neoplastic diseases and vitamin deficiencies were ruled out. Our patient attended five sessions of therapeutic plasma exchange, followed by steroid treatment, intravenous immunoglobulin with minimum recovery of the motor deficit in the upper limbs, but without significant evolution of the motor deficit in the lower limbs. The patient was discharged on maintenance corticotherapy and immunosuppressive treatment with azathioprine. CONCLUSIONS: We report a very rare association between Guillain-Barré syndrome and acute transverse myelitis triggered by a surgical intervention with general anaesthesia. The overlap of Guillain-Barré syndrome and acute transverse myelitis makes the prognosis for recovery worse, and further studies are needed to establish the first-line therapy in these cases.

Gross-total versus near-total resection of large vestibular schwannomas. An institutional experience.

OBJECTIVE: We will report our experience of the surgical treatment of large vestibular schwannomas (VSs). PATIENTS, MATERIALS AND METHODS: We conducted a retrospective study of patients operated on for Koos grade IV VS between 2007 and 2015 at the Department of Neurosurgery, Emergency County Hospital, Târgu Mures, Romania. We studied the general preoperatory clinical data, the preoperative and postoperative facial nerve status, preoperative hearing on the affected side, and any postoperative complications, including death. RESULTS: Sixty-six cases were included in our study. The mean age was 52.95 years and 66.7% (n=44) of the sample were female. All patients had suffered from tinnitus and this had been followed by loss of serviceable hearing on the affected side in 89.4% (n=59) of cases. Preoperative facial palsy was found in 53% (n=35) of patients. The mean tumor size was 40.35 mm. Gross-total resection (GTR) was achieved in 24 (36.36%) cases, while near-total resection (NTR) was obtained in 42 (63.64%) cases. New-onset facial palsy or degradation of the preoperative facial deficit occurred in 12 (18.18%) cases, most of whom were patients with a GTR (n=9, 37.5%). This was statistically significant. There were no significant postoperative differences between the GTR and NTR groups. There was one death in the GTR group. CONCLUSIONS: We conclude that near-total tumor removal provides good surgical results and better postsurgical quality of life for patients when compared to gross-total tumor resection. Therefore, this should be the end goal of the resection of large VSs.

Malignant melanoma - the most severe skin cancer and neurological pathology.

OBJECTIVE: We report our clinical experience with malignant melanoma (MM) patients associated with neurological involvement. PATIENTS, MATERIALS AND METHODS: A database of patients admitted from 2014-2019 in the Ist Clinic of Neurology, Emergency County Hospital of Târgu Mures, Romania, was reviewed to identify patients with MM and neurological involvement. We assessed the demographic and clinical data regarding the neurological disorders and the primary tumor characteristics from the patient registries. Both histopathological and immunohistochemical analysis of the neoplasm was available for the entire cohort. RESULTS: We analyzed 13 982 patient files and 21 met all the inclusion and exclusion criteria. Brain metastases were found in 38.09% of the patients, spinal metastases in 9.52% of the patients, ischemic stroke by cancer-associated thrombosis in 42.85% of the patients and peripheral nervous system involvement in 19.04% of the patients. No statistically significant differences between the four categories of neurological disorders according to socio-demographic parameters, location of the primary tumor, existence of primary tumor ulceration, invasion of the lymph nodes or the presence and location of distant metastasis was found (p>0.05). Our presented patient is the first case of uveal melanoma with hemorrhagic brain metastasis before hepatic involvement. CONCLUSIONS: Neurological involvement in MM encompasses a myriad of variants and while the clinical setting varies from one patient to another, an underlining neoplasia should be evaluated in suspected patients.

Astroblastoma - reviewing literature and one case report.

BACKGROUND: Astroblastoma is a poorly defined central nervous system (CNS) tumor, included along with polar spongioblastoma and gliomatosis cerebri in the group of neuroepithelial tumors of uncertain origin in the June 2016 World Health Organization (WHO) Classification of tumors of the CNS. They are rare neoplasms that affect primarily patients of young ages. The purpose of this research is to highlight the uniqueness and rareness of this pathology and to emphasize on the particularities of one case managed in our Clinic. CASE DESCRIPTION: We present the case of a 54-year-old patient with a history of seizures since the age of six years old, who presented on admission with progressive worsening and unresponsiveness to treatment, starting six months prior to presentation. Brain imaging shows a right frontal mass compressing neighboring structures. Gross total resection of the tumor was performed, and histopathological examination of the surgical sample together with immunohistochemistry highlighted the presence of a low-grade astroblastoma. CONCLUSIONS: We summarized data from the literature in order to highlight aspects of this affliction: clinical presentation, imagery, surgical treatment and pathology, hoping that this will aid physicians in finding useful information on this subject, which can guide them to a good outcome. We also discussed differential diagnosis, as this type of tumor shares common features with ependymoma, meningioma, astrocytoma, etc.

Ectopic intracavernous corticotroph microadenoma: case report of an extremely rare pathology.

Ectopic pituitary adenomas (EPAs) are most likely tumors developing from the cellular remnants following the migration of Rathke's pouch. We present the case of a 54-year-old female diagnosed with Cushing's syndrome. Magnetic resonance imaging (MRI) identified an ectopic microadenoma located in the median wall of the cavernous sinus. Microscopic transsphenoidal surgery was performed and the lesion was completely removed without any postoperative surgical complications. Based on characteristic microscopic and immunohistochemical features and on recent clinicopathological prognostic classifications, the histopathological diagnosis was non-proliferative, non-invasive corticotroph pituitary neuroendocrine tumor, grade 1a. Complete remission of disease was achieved postoperatively and was maintained for one year following surgery. MRI showed complete resection, without tumor recurrence at one and two years. Occurrence of an ectopic intracavenous adrenocorticotropic hormone (ACTH)-secreting adenoma is extremely rare and poses difficulties both in the identification, surgery, histopathological grading, and adequate endocrinological treatment and follow-up.

Lethal Subarachnoid and Intracerebral Haemorrhage Associated with Temporal Arteritis. A Case Report.

Giant cell arteritis is a systemic inflammatory vasculitis, typically involving the superficial temporal arteries, but with possible ischemic and hemorrhagic cerebrovascular complications. The case is reported of a patient with a clinical picture of giant cell arteritis, who had multiple occupational exposures to various infectious agents. His initial favourable progress was followed by an atypical outcome. Despite immunosuppressive treatment, he developed fatal subarachnoid and intracerebral haemorrhages, possibly due to rupture of a microaneurysm of the posterior cerebral artery.

Bilateral Thalamic Glioma: Case Report and Review of the Literature.

Bilateral thalamic glioma is extremely rare and the incidence cannot be adequately expressed. We present the case of a 72 years old male suffering from the rapid deterioration of cognitive function to moderately severe dementia in a short period of time. Magnetic resonance studies demonstrated a bilateral thalamic glioma with a minimal focal gadolinium uptake in the left thalamus. Biopsy was performed and pathology report was of anaplastic astrocytoma, WHO grade III. Radiotherapy was proposed but was rejected by the patient's relatives. The patient deceased 57 days later. We performed an extensive review of the literature and by updating the previous described series we can state that to the best of our knowledge this is the 60th case described in the literature and the second eldest patient presented. Patients suffering from this disease present a poor prognosis, the longest survival described being of 3 years in patients diagnosed with grade II bilateral thalamic glioma. Adjuvant therapy in form of radiotherapy to the thalami is most commonly used but the benefits are unclear. The natural progression of WHO grade III bilateral thalamic glioma left untreated, as can be seen from our case, has an even poorer outcome.

Longitudinally extensive transverse myelitis in neuromyelitis optica: a prospective study of 13 Caucasian patients and literature review.

Neuromyelitis optica (NMO) is a homogenous disease that can be diagnosed by an association of clinical, neuroimaging and serological aspects. We analysed our 4 years NMO series with longitudinally extensive transverse myelitis (LETM) during the disease course. We included consecutive adult Caucasian patients who were diagnosed with definite NMO, or cases of NMO-IgG seropositive LETM considered as limited forms of NMO. Patients included were negative for other diseases (autoimmune, infectious, etc.). We report the Expanded Disability Status Scale (EDSS), brain and spine MRI, CSF, NMO-IgG, treatment, motor and visual outcome. Thirteen cases fulfilled the inclusion criteria, and the mean follow-up period was 3.74 ± 1.8 years. The initial motor deficit was severe with the mean value of motor functional parameter of 4.46 ± 1 and improved at discharge to 2.53 ± 1.4 (p < 0.001). With treatment, the outcome after LETM attack was good in 10 patients, with a significant improvement of the EDSS mainly upon motor deficit, while visual function had a very slight amelioration. The CSF analysis was normal in 8 cases; spinal MRI showed evidence of LETM in all patients while brain MRI was normal in 7. NMO-IgG is a biomarker for NMO that is of diagnostic value in cases of isolated LETM. LETM has a better outcome than ON in NMO Caucasians. Spinal MRI is essential for NMO diagnosis in the presence of LETM and the absence of multiple brain MRI lesions. Maintenance immunosuppressive therapy reduces the frequency of attacks.