MALDI Imaging Mass Spectrometry of High-Grade Gliomas: A Review of Recent Progress and Future Perspective.

Glioblastoma (GBM) is the most common malignancy of the brain with a relatively short median survival and high mortality. Advanced age, high socioeconomic status, exposure to ionizing radiation, and other factors have been correlated with an increased incidence of GBM, while female sex hormones, history of allergies, and frequent use of specific drugs might exert protective effects against this disease. However, none of these explain the pathogenesis of GBM. The most recent WHO classification of CNS tumors classifies neoplasms based on their histopathological and molecular characteristics. Modern laboratory techniques, such as matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry, enable the comprehensive metabolic analysis of the tissue sample. MALDI imaging is able to characterize the spatial distribution of a wide array of biomolecules in a sample, in combination with histological features, without sacrificing the tissue integrity. In this review, we first provide an overview of GBM epidemiology, risk, and protective factors, as well as the recent WHO classification of CNS tumors. We then provide an overview of mass spectrometry workflow, with a focus on MALDI imaging, and recent advances in cancer research. Finally, we conclude the review with studies of GBM that utilized MALDI imaging and offer our perspective on future research.

The COVID-19 Pandemic and Elective Spine Surgery-A Single Center Experience.

Background and objective: The COVID-19 pandemic had a profound impact on medical practice worldwide. In this study, we aimed to investigate the trends of elective spine surgery in our department before and during the pandemic. Materials and methods: Total number of spine procedures due to disc herniation (DH) or spinal stenosis (SS) was collected during 2019-2021 in the Department of Neurosurgery, University Hospital Center Osijek, Croatia. In order to elucidate potential risk factors in the post-pandemic period, demographic data were collected for patients who underwent surgery during 2021. Results: In 2020, there was a 22.1% decrease in the number of surgeries compared to 2019 (205 vs. 263), but during 2021 we observed an increase of 36.1% compared to 2020 (279 vs. 205). The mean age of patients in 2021 was 53.14 years (53.14 ± 13.05) with body mass index of 28.31 kg/m2 (28.31 ± 4.89). There were 179 overweight patients (74%) and 103 smokers (42.6%). Although male and female patients were equally represented (121 each), there was a significant interaction of weight class and sex (p = 0.013). Patients younger than 65 were more likely to undergo surgery due to DH (p < 0.001), whereas older patients were more likely to suffer from SS (p < 0.001). Conclusions: The volume of elective spine surgeries decreased in the first year of the pandemic and increased the following year. Our results suggest that public health policies in the early pandemic period reduced elective surgical procedures, which was followed by a compensatory increase in the following period.

A rare presentation of leiomyosarcoma metastasis to the cervical spine: A case report and a brief review.

Background: Leiomyosarcoma (LMS) is a rare malignancy that originates from smooth muscle. The most common sites of metastases include the lungs, liver, kidney, and skin. Notably, metastases of LMS to the central nervous system/or spine are extremely rare. When a cervical spinal LMS lesion was encountered, the patient successfully underwent gross total tumor resection with negative margins. Case Description: A 63-year-old female had undergone an anterior cervical C5-C7 diskectomy and fusion 18 years ago and resection of a retroperitoneal LMS 3 years ago. She newly presented with right-sided numbness and pain of 2 months duration that correlated with a focal right-sided C5-level hemiparesis (i.e., 4/5 motor strength). When the cervical magnetic resonance demonstrated a right-sided C5 intralaminar mass with extension into the C5-C6 foramen, she underwent posterior tumor resection; pathologically, this proved to be an LMS metastasis. Respectively, 1- and six months postoperatively, follow-up magnetic resonance imaging scans showed no tumor recurrence; she tolerated adjuvant oncological treatment accompanied by physical therapy. However, in one postoperative year, the lesion recurred, and she is presently under consideration for additional surgical management. Conclusion: Gross total surgical resection is the first line of treatment for patients with metastatic LMS. Here, a patient with a C5 laminar/C5-C6 foraminal bony LMS metastasis underwent posterior tumor resection accompanied by adjuvant oncological treatment but exhibited disease recurrence within one postoperative year.

Personalized Treatment of Glioblastoma: Current State and Future Perspective.

Glioblastoma (GBM) is the most aggressive glial tumor of the central nervous system. Despite intense scientific efforts, patients diagnosed with GBM and treated with the current standard of care have a median survival of only 15 months. Patients are initially treated by a neurosurgeon with the goal of maximal safe resection of the tumor. Obtaining tissue samples during surgery is indispensable for the diagnosis of GBM. Technological improvements, such as navigation systems and intraoperative monitoring, significantly advanced the possibility of safe gross tumor resection. Usually within six weeks after the surgery, concomitant radiotherapy and chemotherapy with temozolomide are initiated. However, current radiotherapy regimens are based on population-level studies and could also be improved. Implementing artificial intelligence in radiotherapy planning might be used to individualize treatment plans. Furthermore, detailed genetic and molecular markers of the tumor could provide patient-tailored immunochemotherapy. In this article, we review current standard of care and possibilities of personalizing these treatments. Additionally, we discuss novel individualized therapeutic options with encouraging results. Due to inherent heterogeneity of GBM, applying patient-tailored treatment could significantly prolong survival of these patients.

First Reported Case of Gabriele-de Vries Syndrome with Spinal Dysraphism.

Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease caused by de novo pathogenic variants in the Yin Yang 1 (YY1) gene. Individuals with this syndrome present with multiple congenital anomalies, as well as a delay in development and intellectual disability. Herein, we report the case of a newborn male patient with a novel de novo pathogenic variant in the Guanine Nucleotide-Binding Protein, Alpha Stimulating (GNAS) gene, which was identified by whole-exome sequencing. Our patient suffered from a large open spinal dysraphism which was treated surgically immediately after birth. During the follow-up, facial dysmorphism, bladder and bowel incontinence, and mildly delayed motor and speech development were observed. Congenital central nervous system disorders were also confirmed radiologically. In this case report, we present our diagnostic and treatment approaches to this patient. To our knowledge, this is the first reported case of Gabriele-de Vries syndrome presenting with spinal dysraphism. Extensive genetic evaluation is the cornerstone in treatment of patients with suspected Gabriele-de Vries syndrome. However, in cases with potentially life-threatening conditions, surgery should be strongly considered.

Aggressive Pyogenic Spondylitis Caused by S. constellatus: A Case Report.

Streptococcus constellatus (SC) is a species of Streptococcus belonging to the Streptococcus anginosus group, along with Streptococcus anginosus and Streptococcus intermedius. Despite its commensal nature, underlying risk factors and medical conditions might lead to various anatomic site infections caused by this opportunistic pathogen. Although SC infections have mostly been associated with bacteremia, some case reports of abscess and empyema formation have been documented. Herein, we report a case of a middle-aged female patient who initially presented with radiculopathy symptoms. Subsequent neurologic imaging revealed a pyogenic abscess along paravertebral muscles, which was found to be caused by SC. The patient was successfully treated with abscess drainage from the lumbar zone and antibiotics, and the symptoms of radiculopathy have completely resolved.

Telemedicine in Neurosurgical Trauma during the COVID-19 Pandemic: A Single-Center Experience.

Telemedicine is a rapid tool that reduces the time until treatment for patients, which is especially useful for neurosurgical trauma. The aim of our study was to evaluate the use of telemedicine in neurosurgery during the COVID-19 pandemic compared with the pre-pandemic era. We assessed the utilization of telemedicine at the Department of Neurosurgery at University Hospital Center Osijek in Croatia over a timespan of one year prior to the COVID-19 pandemic and the first year of the pandemic, starting with the date of first lockdown in Croatia. For each time period, the total number of consults and specific clinical inquiries were recorded and adequately grouped as well as comprehensive patient characteristics. There were 336 consults in the pre-pandemic period and 504 in the pandemic period. The number of trauma-related consults during COVID-19 measures was significantly higher than the pre-pandemic era (288 and 138, respectively, p < 0.0001). Neurosurgical trauma patients requiring consults in the pandemic period were significantly older than before the pandemic (64.9 ± 18.5 and 60.6 ± 19.1, respectively, p = 0.03). Significantly, the number of admissions to our center and urgent surgeries did not significantly differ between these periods. Telemedicine is a cost-effective tool in the neurosurgical evaluation of patients, especially for trauma. The COVID-19 pandemic accelerated telemedicine implementation and improved neurosurgical trauma treatments.

Reliability of Ultrasound Measurement of Muscle Thickness in Patients with Supraspinatus Tendon Pathology.

Objectives of the study were to observe supraspinatus muscle thickness in patients with supraspinatus tendon pathology using ultrasound (US) and examining inter- and intra-rater reliability, and to compare muscle thickness with cross-sectional area (CSA) and occupation ratio measured by both US and magnetic resonance imaging (MRI). The investigation was designed as a prospective cohort study. Two groups of patients were included in the study: 43 patients with tendon rupture and 44 patients without tendon rupture as a control group. A written consent was obtained from all patients. In both groups, muscle thickness, CSA and occupation ratio were measured with US, and CSA and occupation ratio with MRI. Study results showed statistically significant between-group differences. The mean supraspinatus muscle thickness measured by US was 14.01 mm and 19.83 mm in patients with and without tendon rupture, respectively. CSA and occupation ratio measured by US and MRI also showed statistically significant between-group differences. Pearson correlation coefficient between supraspinatus thickness and occupation ratio and CSA measured by US and MRI showed strong to moderate correlation. US measurements showed moderate to strong intra- and inter-rater reliability. In conclusion, supraspinatus muscle thickness measurement by US is a reliable method for muscle atrophy evaluation and strongly correlates with other acknowledged methods.

Measurable and Unmeasurable Features of Ultrasound Lymph Node Images in Detection of Malignant Infiltration.

The aim of the study was to assess diagnostic value and utility of selected morphological features in predicting lymph node (LN) malignancy using B-mode, Doppler ultrasonography and multivariate settings in a tertiary radiological referral center. The study included 123 patients having undergone ultrasound-guided fine-needle aspiration and cytologic analysis (FNAC) of cervical, axillary and inguinal LNs. Each LN was characterized by long/L and short/T-axis, shape, margins, echogenicity, cortical thickness, vascularization, and examiner's subjective impression. Within the limitations of FNAC, altered shape and vascularization had relatively high specificity and positive predictive value (>80%), whereas subjective impression had high sensitivity and negative predictive value (100%) for malignancy. The cut-off levels for different features of LN by ROC analysis were as follows: long-axis 23 mm, short-axis 11 mm, L/T ratio 2.19, and maximal cortical thickness 5.1 mm. On multivariate analysis (adaptive regression splines, n=108), the addition of long-axis, L/T ratio, age and sex considerably improved diagnostic accuracy (88%), sensitivity (margins + vascularization) and specificity (subjective impression) of the diagnostic model. The combination of morphological and demographic features could improve diagnostic accuracy, usually with a trade-off between the sensitivity and specificity of the predictive model. The performance may depend on the level of expertise and institutional settings.

Cervical dystonia and quality of life.

Cervical dystonia is focal dystonia characterized by involuntary movement of the neck muscle, which leads to abnormal head posture. It can be accompanied with pain and tremor. In this study, we evaluated the presence of depression and anxiety in patients with cervical dystonia and the influence of dystonia symptoms on the quality of life. Psychiatric symptoms were evaluated by use of the Beck Depression Inventory (BDI-II) and Beck Anxiety Inventory. Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was used to evaluate the cervical dystonia symptoms. Quality of life was assessed by the craniocervical dystonia questionnaire (CDQ-24) and short form 36 health survey (SF-36). Nineteen patients were analyzed. Most of the patients had mild cervical dystonia (mean TWSTRS 23.89). Depression was present in 42.1 % and anxiety in 57.9 % of the patients. Disability due to cervical dystonia correlated with the occurrence of depression (ρ = 0.534) and anxiety (r = 0.652). Disability was found to significantly influence the stigma, emotional state, pain, daily activity, social life, physical function, and physical and mental disability. Pain influenced some aspects of body pain, physical function, and physical and mental disability. Being associated with disability and pain, cervical dystonia decreases the quality of life in many aspects. Disability also influenced depression and anxiety, which were present in half of study patients. In addition to follow up for cervical dystonia symptoms, patients with cervical dystonia should also be assessed for psychiatric symptoms on routine clinical check-ups. In addition to botulinum toxin, psychopharmaceuticals should be considered as a treatment option in these patients.