A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with TPR-NTRK1 Fusion Treated with Larotrectinib

Herein, we present a rare case of a nine-month-old boy diagnosed with infant-type hemispheric glioma (gliosarcoma subtype) at the left frontal lobe. Following subtotal resection, the patient started chemotherapy with the BABY POG protocol. We describe the clinical diagnosis, histological characteristics, radiological features, molecular aspects, and management of this tumor. A comprehensive molecular analysis on the tumor tissue showed a <i>TPR-NTRK1</i> gene fusion. The patient was treated with a TRK inhibitor, larotrectinib, and exhibited a stable disease with residual lesion following 8 months of target therapy. The present study is the first report of an infantile gliosarcoma harboring <i>NTRK1</i> rearrangement treated with larotrectinib.

Peripheral inflammatory markers associated with brain-volume reduction in patients with bipolar I disorder

Background: Neuroinflammation and brain structural abnormalities are found in bipolar disorder (BD). Elevated levels of cytokines and chemokines have been detected in the serum and cerebrospinal fluid of patients with BD. This study investigated the association between peripheral inflammatory markers and brain subregion volumes in BD patients. Methods: Euthymic patients with bipolar I disorder (BD-I) aged 20 to 45 years underwent whole-brain magnetic resonance imaging. Plasma levels of monocyte chemoattractant protein-1, chitinase-3-like protein 1 (also known as YKL-40), fractalkine, soluble tumor necrosis factor receptor-1 (sTNF-R1), interleukin-1β, and transforming growth factor-β1 were measured on the day of neuroimaging. Clinical data were obtained from medical records and interviewing patients and reliable others. Results: We recruited 31 patients with a mean age of 29.5 years. In multivariate regression analysis, plasma level YKL-40, a chemokine, was the most common inflammatory marker among these measurements displaying significantly negative association with the volume of various brain subareas across the frontal, temporal, and parietal lobes. Higher YKL-40 and sTNF-R1 levels were both significantly associated with lower volumes of the left anterior cingulum, left frontal lobe, right superior temporal gyrus and supramarginal gyrus. A greater number of total lifetime mood episodes was also associated with smaller volumes of the right caudate nucleus and bilateral frontal lobes. Conclusions: The volume of brain regions known to be relevant to BD-I may be diminished in relation to higher plasma level of YKL-40, sTNF-R1, and more lifetime mood episodes. Macrophage and macrophage-like cells may be involved in brain volume reduction among BD-I patients.

An explainable Artificial Intelligence approach to study MCI to AD conversion via HD-EEG processing

An explainable Artificial Intelligence (xAI) approach is proposed to longitudinally monitor subjects affected by Mild Cognitive Impairment (MCI) by using high-density electroencephalography (HD-EEG). To this end, a group of MCI patients was enrolled at IRCCS Centro Neurolesi Bonino Pulejo of Messina (Italy) within a follow-up protocol that included two evaluations steps: T0 (first evaluation) and T1 (three months later). At T1, four MCI patients resulted converted to Alzheimer’s Disease (AD) and were included in the analysis as the goal of this work was to use xAI to detect individual changes in EEGs possibly related to the degeneration from MCI to AD. The proposed methodology consists in mapping segments of HD-EEG into channel-frequency maps by means of the power spectral density. Such maps are used as input to a Convolutional Neural Network (CNN), trained to label the maps as “T0” (MCI state) or “T1” (AD state). Experimental results reported high intra-subject classification performance (accuracy rate up to 98.97% (95% confidence interval: 98.68–99.26)). Subsequently, the explainability of the proposed CNN is explored via a Grad-CAM approach. The procedure allowed to detect which EEG-channels (i.e., head region) and range of frequencies (i.e., sub-bands) resulted more active in the progression to AD. The xAI analysis showed that the main information is included in the delta sub-band and that, limited to the analyzed dataset, the highest relevant areas are: the left-temporal and central-frontal lobe for Sb01, the parietal lobe for Sb02, the left-frontal lobe for Sb03 and the left-frontotemporal region for Sb04.

Intraoperative Rupture of an Intracranial, Extradural Hydatid Cyst: Case Report and Treatment Options

A 23-year-old woman was presented to the Emergency Unit with intracranial hypertension syndrome and blindness in her left eye which had started recently. A cranial native computed tomography scan and a magnetic resonance imaging (MRI) with contrast examinations revealed a giant intracranial cystic lesion, extending into the left frontal lobe, which was compressing the optic chiasm and eroding the internal plate of the left frontal bone. Surgical craniotomy was performed for evacuation and decompression, but during the craniotomy the cyst ruptured. After assessing the degree of erosion of the internal bone plate, we concluded that the primary origin of the cyst was intraosseous. With the dura mater being intact, abundant lavage with H2O2 was applied and the bone flap was replaced after rigorous bone scraping. Imaging control at six and twelve months identified no recurrence of the cyst. In the literature, hydatid cysts located in the skull bone are very rare and most of them rupture intraoperatively. Given their extremely low incidence in developed countries, any neurosurgeons’ experience with such pathology is limited and in some cases surgery cannot be delayed. In the case of intracerebral hydatid cysts, a neurosurgeon usually has only one shot at surgery, so simple and quick-to-access therapeutic guidelines must be developed in order to inform the choice of surgical technique. We conclude that the most successful surgical approach could be double concentric craniotomy. This surgical technique is used in intracerebral tumors, which also have an important bone invasion.

MNG-2 Meningioma with aseptic meningitis

The patient, a woman in her seventies, visited the Department of Neurology at our hospital one month ago with transient right hemiparesis, and was referred to our department because a CT scan showed a 4cm extramedullary lesion in the left convexity. She was judged to have symptomatic epilepsy associated with the lesion and was started on antiepileptic drugs. The lesion showed low signal on T1WI, equal signal on T2WI, and homogeneous contrast on Gd contrast T1WI, suggesting a meningioma, but the surrounding left frontal lobe subarachnoid space was also contrasted, suggesting the possibility of seeding or other diseases. After that, the contrast area of the subarachnoid space increased in a short period of time, and the control of epileptic seizures was poor. Preoperative spinal fluid examination showed an elevated cell count and findings of aseptic meningitis. A left parietal craniotomy was performed to remove the extramedullary tumor as much as possible. The subarachnoid space of the left frontal lobe adjacent to the tumor was covered with extensive pale yellow apparently abscess-like tissue. The pathological diagnosis of the extramedullary tumor was angiomatous meningioma (WHO Grade 1), and the pale yellow tissue that filled the subarachnoid space was necrotic tissue containing neutrophils and no tumor component. IgG4 was positive in about 10% of the tumor. The postoperative course of the patient was good, the contrast area of the left frontal lobe subarachnoid space was reduced on MRI, aseptic meningitis was improved, and she was discharged home with no neurological deficits. The patient has been under outpatient observation for 2 years without recurrence of aseptic meningitis or appearance of contrast-enhancing lesions in the subarachnoid space. This case is thought to be a possible IgG4-related disease, and we report it with a discussion of the literature.

White Matter Hyperintensity Distribution Differences in Aging and Neurodegenerative Disease Cohorts

Introduction: White matter hyperintensities (WMHs) are common magnetic resonance imaging (MRI) findings in the aging population in general, as well as in patients with neurodegenerative diseases. They are known to exacerbate the cognitive deficits and worsen the clinical outcomes in the patients. However, it is not well-understood whether there are disease-specific differences in prevalence and distribution of WMHs in different neurodegenerative disorders. Methods: Data included 976 participants with cross-sectional T1-weighted and fluid attenuated inversion recovery (FLAIR) MRIs from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort of the Canadian Consortium on Neurodegeneration in Aging (CCNA) with eleven distinct diagnostic groups: cognitively intact elderly (CIE), subjective cognitive impairment (SCI), mild cognitive impairment (MCI), vascular MCI (V-MCI), Alzheimers dementia (AD), vascular AD (V-AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), cognitively intact elderly with Parkinsons disease (PD-CIE), cognitively impaired Parkinsons disease (PD-CI), and mixed dementias. WMHs were segmented using a previously validated automated technique. WMH volumes in each lobe and hemisphere were compared against matched CIE individuals, as well as each other, and between men and women. Results: All cognitively impaired diagnostic groups had significantly greater overall WMH volumes than the CIE group. Vascular groups (i.e. V-MCI, V-AD, and mixed dementia) had significantly greater WMH volumes than all other groups, except for FTD, which also had significantly greater WMH volumes than all non-vascular groups. Women tended to have lower WMH burden than men in most groups and regions, controlling for age. The left frontal lobe tended to have a lower WMH burden than the right in all groups. In contrast, the right occipital lobe tended to have greater WMH loads than the left. Conclusions: There were distinct differences in WMH prevalence and distribution across diagnostic groups, sexes, and in terms of asymmetry. WMH burden was significantly greater in all neurodegenerative dementia groups, likely encompassing areas exclusively impacted by neurodegeneration as well as areas related to cerebrovascular disease pathology.

Management of Ruptured Arteriovenous Malformation During Pregnancy- Case Report.

Background: Over the years care of pregnant woman has improved all over the world. However, still a significant percentage of the causes of pregnant mortality are subarachnoid haemorrhages due to rupture of arteriovenous malformation (AVM). According to available data, the percentage is as high as 5-12%. Neurosurgical operations in pregnant women require the cooperation of doctors of many specializations and are associated with close supervision of the patient due to the increased risk of complications. There are no guidelines regarding brain hemorrhages in pregnancy. This is the reason why case reports in this field are valuable as source of medical knowledge.Case presentation: A 28-year-old patient was admitted in a severe condition, GCS: 3, to the ICU due to massive intracerebral bleeding with a puncture into the ventricular system from the AVM in left frontal lobe. The family informed about the possibility of patient’s pregnancy, TVUS was performed and the sixth week fetus was visualized in the uterus. After gynaecological and neurosurgical consultation the successful surgery was made.The patient was hospitalized for 5 months at the ICU. The stay was complicated by pneumonia and an urinary tract infection that were successfully cured. The patient was under supervision of gynaecologists, the pregnancy was developing properly, tests were carried out as recommended. The patient underwent psychotherapy, rehabilitation and music therapy.At 35th week of gestation elective caesarean section was performed. A female infant of 2400 g was born, on the Apgar scale in 1st, 3rd, 5th minutes, 6,10,10 points respectively. Labour was complicated by mothers seizures and respiratory distress. After three days the patient's condition improved. Currently patient is rehabilitated as an outpatient.Conclusions: The above case emphasizes the need for cooperation between many specialties, physiotherapists and midwives, which enabled effective therapy of a pregnant woman and saving her life in such a critical situation. In addition interdisciplinary treatment ended positively for both mother and child.

Case Report: Unusual Clinical Presentation of a Rare Cardiac Inflammatory Myofibroblastic Tumor in Children: The Differential Diagnosis With Pediatric Emergencies

Introduction: There are still no guidelines about pediatric cardiac cancers. The purpose of this work is to provide new scientific data facilitating the differential diagnosis of a rare cardiac tumor with an unusual presentation, such as the cardiac inflammatory myofibroblastic tumor (IMT).Case Presentation: A 3-year-old male child presented with several symptoms including unconsciousness, vomiting, and drowsiness. A clinical and neurological examination revealed a unilateral (right) motor delay and positive unilateral Babinski sign. Electrocardiogram (ECG) was normal.Diagnostic Assessment: The total body computed tomography (CT) scans showed hypodensity in the left temporal–parietal lobe, a large hypodense area in the right frontal lobe, and a second area in the left frontal lobe were found with head CT. A magnetic resonance (MR) also noted cerebral areas of hypointensity. The echocardiographic images revealed an ovoid mass, adherent to the anterolateral papillary muscle. The histological exams, performed with hematoxylin–eosin, Masson's trichrome, Alcian blue PAS, Weigert and Van-Gieson stain, allowed observing the microscopic structure of the neoplastic mass. The immunohistochemical analysis was performed through subsequent antibodies: anti-vimentin, anti-actina, anti-ALK, anti-CD8, anti-CD3, anti-CD20, anti-kappa and lambda chains, and anti CD68 antibodies. The healthcare professionals diagnosed a cardiac IMT with brain embolism.Differential Diagnosis: The ventricular localization, observed through radiological exams, required a differential diagnosis with fibroma and rhabdomyoma, the presence of brain embolism with sarcoma, and its morphology with fibroma. Neurological symptoms might be attributed to encephalitis, primitive cerebral cancer, such as astrocytoma or neuroblastoma, cerebral metastases due to any malignancy, or embolic stroke.Conclusion: New studies are encouraged to better define IMT behavior and draw up guidelines confirming the crucial role of multidisciplinary approach and treatment protocol selected on the basis of the characteristics of the tumors, in the case of this rare type of cancer.

Integrated space–frequency–time domain feature extraction for MEG-based Alzheimer’s disease classification

Magnetoencephalography (MEG) has been combined with machine learning techniques, to recognize the Alzheimer’s disease (AD), one of the most common forms of dementia. However, most of the previous studies are limited to binary classification and do not fully utilize the two available MEG modalities (extracted using magnetometer and gradiometer sensors). AD consists of several stages of progression, this study addresses this limitation by using both magnetometer and gradiometer data to discriminate between participants with AD, AD-related mild cognitive impairment (MCI), and healthy control (HC) participants in the form of a three-class classification problem. A series of wavelet-based biomarkers are developed and evaluated, which concurrently leverage the spatial, frequency and time domain characteristics of the signal. A bimodal recognition system based on an improved score-level fusion approach is proposed to reinforce interpretation of the brain activity captured by magnetometers and gradiometers. In this preliminary study, it was found that the markers derived from gradiometer tend to outperform the magnetometer-based markers. Interestingly, out of the total 10 regions of interest, left-frontal lobe demonstrates about 8% higher mean recognition rate than the second-best performing region (left temporal lobe) for AD/MCI/HC classification. Among the four types of markers proposed in this work, the spatial marker developed using wavelet coefficients provided the best recognition performance for the three-way classification. Overall, the proposed approach provides promising results for the potential of AD/MCI/HC three-way classification utilizing the bimodal MEG data.