Brainstem Research Articles

Traumatic Delayed Posterior Cranial Fossa Epidural Hematoma: A Rare Entity

AbstractPosterior fossa epidural hematomas (EDHs) are much rarer entities than supratentorial EDHs which are reported only 4 to 7% in the literature. Due to the tight space and critical structures in posterior fossa, only a few cases can go with the conservative management but even then patients can deteriorate anytime with enlargement of hematoma and compression effects on brain stem and require urgent evacuation. This letter aims to provide a case of a young kid who presented initially with less-volume EDH and later required urgent evacuation because of hematoma expansion.

Brain Stem Hemorrhage after Insertion of a Lumbar Drain: An Extremely Rare but Fatal Complication of a Routine Procedure

AbstractDecompressive craniectomy (DC) is a life-saving procedure to control refractory intracranial pressure after traumatic brain injury. Postdecompressive craniectomy hydrocephalus (PDCH) is debilitating complication following DCs. Lumbar drainage (LD) is a temporary measure that is helpful in the assessment of PDCH and its functioning can predict the risks and benefits of definitive cerebrospinal fluid (CSF) diversion procedures. LD is associated with multiple complications. Intracranial hemorrhage is a rare but devastating complication following LD. Here, the authors report a case in which LD was performed as a temporary measure to assess PDCH, resulting in brain stem hemorrhage (BSH). A 45-year-old male underwent DC for severe traumatic brain injury. Patient developed PDCH in postoperative period. LD was done as a bridging procedure for definitive CSF diversion procedure, which resulted in fatal BSH. Authors conclude that although a simple procedure, LD can be associated with fatal BSH. Since drainage of CSF after LD is unpredictable in patients of PDCH, a close monitoring of the functioning of the LD system is required to avoid overdrainage and brain herniations.

Single-Center Experience in Microsurgical Resection of Acoustic Neurinomas and the Benefit of Microscope-Based Augmented Reality.

Background and Objectives: Microsurgical resection with intraoperative neuromonitoring is the gold standard for acoustic neurinomas (ANs) which are classified as T3 or T4 tumors according to the Hannover Classification. Microscope-based augmented reality (AR) can be beneficial in cerebellopontine angle and lateral skull base surgery, since these are small areas packed with anatomical structures and the use of this technology enables automatic 3D building of a model without the need for a surgeon to mentally perform this task of transferring 2D images seen on the microscope into imaginary 3D images, which then reduces the possibility of error and provides better orientation in the operative field. Materials and Methods: All patients who underwent surgery for resection of ANs in our department were included in this study. Clinical outcomes in terms of postoperative neurological deficits and complications were evaluated, as well as neuroradiological outcomes for tumor remnants and recurrence. Results: A total of 43 consecutive patients (25 female, median age 60.5 ± 16 years) who underwent resection of ANs via retrosigmoid osteoclastic craniotomy with the use of intraoperative neuromonitoring (22 right-sided, 14 giant tumors, 10 cystic, 7 with hydrocephalus) by a single surgeon were included in this study, with a median follow up of 41.2 ± 32.2 months. A total of 18 patients underwent subtotal resection, 1 patient partial resection and 24 patients gross total resection. A total of 27 patients underwent resection in sitting position and the rest in semi-sitting position. Out of 37 patients who had no facial nerve deficit prior to surgery, 19 patients were intact following surgery, 7 patients had House Brackmann (HB) Grade II paresis, 3 patients HB III, 7 patients HB IV and 1 patient HB V. Wound healing deficit with cerebrospinal fluid (CSF) leak occurred in 8 patients (18.6%). Operative time was 317.3 ± 99 min. One patient which had recurrence and one further patient with partial resection underwent radiotherapy following surgery. A total of 16 patients (37.2%) underwent resection using fiducial-based navigation and microscope-based AR, all in sitting position. Segmented objects of interest in AR were the sigmoid and transverse sinus, tumor outline, cranial nerves (CN) VII, VIII and V, petrous vein, cochlea and semicircular canals and brain stem. Operative time and clinical outcome did not differ between the AR and the non-AR group. However, use of AR improved orientation in the operative field for craniotomy planning and microsurgical resection by identification of important neurovascular structures. Conclusions: The single-center experience of resection of ANs showed a high rate of gross total (GTR) and subtotal resection (STR) with low recurrence. Use of AR improves intraoperative orientation and facilitates craniotomy planning and AN resection through early improved identification of important anatomical relations to structures of the inner auditory canal, venous sinuses, petrous vein, brain stem and the course of cranial nerves.

From periphery to center, untold story of pure neuritic leprosy: an electrophysiological study.

Pure neuritic leprosy (PNL) is uncommon form of leprosy involving peripheral nerves. Some isolated case reports have shown imaging changes in the central nervous system (CNS) and also impairment in visual evoked potential (VEP), somatosensory evoked potential (SSEP) and brain stem auditory-evoked potentials (BAEPs) parameters in PNL, but there is lack of large study. This prospective observational study evaluates impairment in these central conduction studies among PNL patients. We screened patients with leprosy presenting with features of neuropathy and/or thickened nerves. Patients with bacilli-positive nerve biopsies were included in the study and subjected to routine tests along with nerve conduction study (NCS), VEP, tibial SSEP and BAEPs. Parameters of these studies were analyzed based on data from previous studies. Of 76 patients screened for PNL 49 had positive findings in biopsy. Most of patients were male and mean age group was 46.35 ± 15.35years. Mononeuritis multiplex was most common NCS pattern in 46.93% (23/49) patients. We found abnormal VEP in 13 out of 35 patients (37.14%). Similarly abnormal SSEP and BAEPs among 42.85% and 40% patients respectively. This study shows that in PNL significant number of patients have subclinical CNS involvement. Exact pathophysiology of CNS involvement is not known till now but study of VEP, SSEP and BAEPs parameter may help in early diagnosis of PNL.

Defects of Midbrain/Hindbrain Development: Defects of Anteroposterior and Dorsoventral Patterning

AbstractThe knowledge regarding the midbrain and the hindbrain (MBHB) malformations has been progressively increased in recent years, thanks to the advent of neuroimaging and genetic technologies. Many classifications have been proposed in order to well describe all of these patterns. The most complete and detailed one is based on the genetic and embryologic features that allow an easier and effective knowledge of these disturbs. It categorizes them into four primary groups: (1) Malformations resulting from early anteroposterior and dorsoventral patterning defects or the misspecification of MBHB germinal zones.(2) Malformations linked to later generalized developmental disorders that notably impact the brain stem and cerebellum, with a pathogenesis that is at least partially comprehended.(3) Localized brain malformations significantly affecting the brain stem and cerebellum, with a pathogenesis that is partly or largely understood, encompassing local proliferation, migration, and axonal guidance.(4) Combined hypoplasia and atrophy observed in presumed prenatal-onset degenerative disorders. Regarding diagnosis, brain stem malformations are typically identified during prenatal assessments, particularly when they are linked with anomalies in the cerebellum and cerebrum. Magnetic resonance imaging is the primary neuroimaging method in the evaluation of these malformations. The clinical characteristics of individuals with malformations in the midbrain or hindbrain are generally nonspecific. Common findings at presentation are hypotonia, motor retardation, ataxia, variable degree of intellectual disability, and abnormal eye movement (e.g., nystagmus, abnormal saccades, oculomotor apraxia, strabismus, and abnormal smooth pursuit). The complexity and the number of these MBHB malformations are constantly increasing. We will provide an overview of MBHB disorders, focusing on embryology, genetic, clinical, and neuroradiology features that could be helpful for clinicians and neuroscientist to understand process of these conditions.

Pure downgaze palsy from isolated infarction of the left paramedian thalamic-mesencephalon junction.

A 65-years-old female was hospitalized 24 h after experiencing the sudden onset of subjective reduction in visual acuity and hypersomnia. On admission to the neurological ward, she presented isolated downgaze palsy. A Magnetic Resonance Imaging of the brain disclosed a discrete, ovalar hyperintensity involving the left paramedian thalamic-mesencephalon junction. The lesion was consistent with infarction. Isolated downgaze palsy has been described in thrombosis of Artery of Percheron leading to infarction of bilateral paramedian thalami along with structures from the mesencephalic-diencephalic junction such as the Medial Longitudinal Fasciculus (riMLF). While neurons from the riMLF controlling upward vertical saccades project to either ipsilateral and contralateral oculomotor nuclear complexes, those involved in regulating downgaze descend ipsilaterally in the brain stem. Isolated downgaze palsy has an extreme localizer value to the diencephalic-mesencephalon junction and can arise from a unilateral lesion.

Interoceptive training impacts the neural circuit of the anterior insula cortex

Interoception is the perception of afferent information that arises from anywhere and everywhere within the body. Recently, interoceptive accuracy could be enhanced by cognitive training. Given that the anterior insula cortex (AIC) is a key node of interoception, we hypothesized that resting functional connectivity (RSFC) from AIC was involved in an effect of interoceptive training. To address this issue, we conducted a longitudinal intervention study using interoceptive training and obtained RSFC using fMRI before and after the intervention. A heartbeat perception task evaluated interoceptive accuracy. Twenty-two healthy volunteers (15 females, age 19.9 ± 2.0 years) participated. After the intervention, interoceptive accuracy was enhanced, and anxiety levels and somatic symptoms were reduced. Also, RSFC from AIC to the dorsolateral prefrontal cortex (DLPFC), superior marginal gyrus (SMG), anterior cingulate cortex (ACC), and brain stem, including nucleus tractus solitarius (NTS) were enhanced, and those from AIC to the visual cortex (VC) were decreased according to enhanced interoceptive accuracy. The neural circuit of AIC, ACC, and NTS is involved in the bottom-up process of interoception. The neural circuit of AIC, DLPFC, and SMG is involved in the top-down process of interoception, which was thought to represent the cognitive control of emotion. The findings provided a better understanding of neural underpinnings of the effect of interoceptive training on somatic symptoms and anxiety levels by enhancing both bottom-up and top-down processes of interoception, which has a potential contribution to the structure of psychotherapies based on the neural mechanism of psychosomatics.

Clinical Characteristics and Delayed Diagnosis of Pediatric Patients Presenting to the Emergency Department With a Newly Diagnosed Central Nervous System Tumor: A Single Institutional Experience.

Due to the varied symptomatology and inconsistent features on neurologic exam, central nervous system (CNS) tumors are difficult to diagnosis in a timely manner. To determine the clinical, neurological, and neuroimaging features of newly diagnosed CNS tumors presenting to the emergency department (ED). We evaluated a retrospective cohort of 121 consecutive patients presenting to a tertiary care pediatric ED over 7 consecutive years with newly diagnosed CNS tumors. Clinical symptomatology, neurologic findings reported by emergency room and neurology physicians, neuroimaging features, and time to diagnosis were analyzed. A total of 116 (48 female, median age 8.0 years (interquartile range, 4.4-12.6), 52% Hispanic) presented to the ED (64% self-referred) diagnosed with a brain tumor (54% posterior fossa, 24% embryonal, 24% low-grade glioma, 16% high-grade glioma) resulting in hospital admission in 92% of cases. Five were diagnosed with extradural spinal, clivus, or orbital apex tumors. Symptomatology or duration did not differ when stratified by demographics, location, or histologic subtype. Moderate degree of concordance was observed among neurologic examinations performed by ED physicians and neurologists. Delayed diagnosis (median delay = 3.5 [1-7] months) was seen in 14% of patients, 13 with primary brain tumors (11 hemispheric, 2 brain stem). Six children with delayed diagnosis of low-grade glial tumors had a nonfocal neurologic examination in comparison to 5 patients with abnormal examinations observed with primary spinal or extradural CNS tumors. Four patients with posterior fossa tumors (3 medulloblastoma, 1 ependymoma) had normal/near normal neurologic examination at presentation despite posterior fossa symptomatology related to increased intracranial pressure. Our series highlights the complexity of symptomology and neurologic findings in children presenting to the ED with newly diagnosed CNS tumors who may have a normal neurologic examination. Standardization of symptom assessment and focused neurologic examinations may lead to earlier neuroimaging and prevent delayed diagnosis.

EEG Innovations in Neurological Disorder Diagnostics: A Five-Year Review

The study provides a description of electroencephalography (EEG) advancements and their application in diagnosing and assessing various neurological diseases over the previous five years. The paper covers how EEG is used to examine epilepsy, sleep disorders, movement disorders, cognitive function, and brain damage. In epilepsy, EEG remains critical for seizure diagnosis, categorization, and localization of epileptogenic zones. Recent enhancements include the integration of machine learning techniques with high-density EEG equipment. In terms of sleep disorders, aberrant patterns suggestive of illnesses such as sleep apnea or narcolepsy may be diagnosed by a sleep architecture study utilizing EEGs, which can also be used to track therapy response. Cortical involvement occurs in Parkinson’s disease and Huntington’s disease, as well as other areas of the brain stem or basal ganglia. It helps researchers learn more about the cortical damage produced by these disorders, which contributes greatly to understanding their pathophysiology. Aside from that, cognitive evaluation based on EEG has evolved via the creation of quantifiable biomarkers for early identification and monitoring of deterioration in Alzheimer’s disease, among others. Traumatic injuries can damage brain functioning, hence knowledge regarding severity predicted outcomes can be acquired by Traumatic Brain Injury evaluation utilizing EEG.

Immortalization and Characterization of GFAP-expressing Glial Cells from the Adult Mouse Hypothalamus, Cortex, and Brain Stem

The generation of astrocyte cell lines from the hypothalamus is key to study glial involvement in hypothalamic physiology, including energy homeostasis. As such, we immortalized astrocytes from the hypothalamus of an adult male CD-1 mouse using SV40 T-antigen to generate the mHypoA-Ast1 cell line. A comparative approach was taken with two other murine GFAP-expressing cell lines that were also generated in this study: a mixed glial cell line from the cortex (mCortA-G1) and an oligodendrocyte cell line from the brainstem (mBstA-Olig1), as well as an established microglial cell line (IMG). mHypoA-Ast1 cells express GFAP, alongside other astrocytic markers such as Aldh1l1, Aqp4, Glt1 and S100b, and express low levels of microglial, ependymal and oligodendrocyte markers. 100 ng/mL lipopolysaccharide (LPS) elevated mRNA levels of Il6, Il1b, Tnfα and Cxcl5 in mHypoA-Ast1 cells after 4 h, while 50 μM palmitate increased Il6 and Chop mRNA, demonstrating the ability of these cells to respond to inflammatory and nutrient signals. Interestingly, co-culture of mHypoA-Ast1 cells with mHypoE-N46 hypothalamic neuronal cells prevented the palmitate-mediated increase in orexigenic neuropeptide Agrp mRNA in mHypoE-N46 cells, suggesting that this cell line can alter neuronal responses to nutrients. In conclusion, we report mHypoA-Ast1 cells representing a functional astrocyte cell line from the adult mouse brain that can be used to study the complex interactions of hypothalamic cells, as well as dysregulation that may occur in disease states, providing a key tool for neuroendocrine research.

Assessment of Deafness in Term Infants with Birth Asphyxia with Otoacoustic Emission and Brain Stem Evoked Response Audiometry: A Prospective Observational Study

Assessment of Deafness in Term Infants with Birth Asphyxia with Otoacoustic Emission and Brain Stem Evoked Response Audiometry: A Prospective Observational Study

Does Time to Asystole in Donors After Circulatory Death Impact Recipient Outcome in Liver Transplantation?

The agonal phase can vary following treatment withdrawal in donor after circulatory death (DCD). There is little evidence to support when procurement teams should stand down in relation to donor time to death (TTD). We assessed what impact TTD had on outcomes following DCD liver transplantation. Data were extracted from the UK Transplant Registry on DCD liver transplant recipients from 2006 to 2021. TTD was the time from withdrawal of life-sustaining treatment to asystole, and functional warm ischemia time was the time from donor systolic blood pressure and/or oxygen saturation falling below 50 mm Hg and 70%, respectively, to aortic perfusion. The primary endpoint was 1-y graft survival. Potential predictors were fitted into Cox proportional hazards models. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. One thousand five hundred fifty-eight recipients of a DCD liver graft were included. Median TTD in the entire cohort was 13 min (interquartile range, 9-17 min). Restricted cubic splines revealed that the risk of graft loss was significantly greater when TTD ≤14 min. After 14 min, there was no impact on graft loss. Prolonged hepatectomy time was significantly associated with graft loss (hazard ratio, 1.87; 95% confidence interval, 1.23-2.83; P = 0.003); however, functional warm ischemia time had no impact (hazard ratio, 1.00; 95% confidence interval, 0.44-2.27; P > 0.9). A very short TTD was associated with increased risk of graft loss, possibly because of such donors being more unstable and/or experiencing brain stem death as well as circulatory death. Expanding the stand down times may increase the utilization of donor livers without significantly impairing graft outcome.

Classical BSE dismissed as the cause of CWD in Norwegian red deer despite strain similarities between both prion agents

The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD reindeer and CWD moose and from North American CWD. The isolate showed nevertheless features similar to the classical BSE (BSE-C) strain. Furthermore, BSE-C could not be excluded based on the PrPSc immunohistochemistry staining in the brainstem and the absence of detectable PrPSc in the lymphoid tissues. Because of the known ability of BSE-C to cross species barriers as well as its zoonotic potential, the CWD red deer isolate was submitted to the EURL Strain Typing Expert Group (STEG) as a BSE-C suspect for further investigation. In addition, different strain typing in vivo and in vitro strategies aiming at identifying the BSE-C strain in the red deer isolate were performed independently in three research groups and BSE-C was not found in it. These results suggest that the Norwegian CWD red deer case was infected with a previously unknown CWD type and further investigation is needed to determine the characteristics of this potential new CWD strain.

Expanding phenotype of MED13-associated syndrome presenting novel de novo missense variant in a patient with multiple congenital anomalies

BackgroundWhole exome sequencing allows rapid identification of causative single nucleotide variants and short insertions/deletions in children with congenital anomalies and/or intellectual disability, which aids in accurate diagnosis, prognosis, appropriate therapeutic interventions, and family counselling. Recently, de novo variants in the MED13 gene were described in patients with an intellectual developmental disorder that included global developmental delay, mild congenital heart anomalies, and hearing and vision problems in some patients.ResultsHere we describe an infant who carried a de novo p.Pro835Ser missense variant in the MED13 gene, according to whole exome trio sequencing. He presented with congenital heart anomalies, dysmorphic features, hydrocephalic changes, hypoplastic corpus callosum, bilateral optic nerve atrophy, optic chiasm atrophy, brain stem atrophy, and overall a more severe condition compared to previously described patients.ConclusionsTherefore, we propose to expand the MED13-associated phenotype to include severe complications that could end up with multiple organ failure and neonatal death.

The influence of a course of complex application of supravenous laser irradiation of blood and phototherapy on indicators of the neurohormonal status of patients with true eczema

BACKGROUND: In the pathogenesis of true eczema, an important place is occupied by stress, under the influence of which stimulation of the hypothalamus and brain stem occurs, as well as activation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. Stress-induced secretion of neurotransmitters impairs the barrier function of the epidermis, slows wound healing, increases itching and inflammation, and suppresses immunity by changing the immune response of T-helper cells. AIM: Assessment of the severity of the corrective effect of a course of application of supravenous laser irradiation of blood and broadband medium-wave phototherapy on the blood levels of adrenocorticotropin, cortisol and beta-endorphin in patients with true eczema with a moderate form of the course. MATERIALS AND METHODS: The study was carried out with the participation of 120 patients with a moderate form of true eczema. Using simple fixed randomization, all patients were divided into 4 groups. The first group (control, n=30) received only basic drug therapy, including the use of detoxification, hyposensitizing, antihistamines and topical glucocorticosteroids. Patients of the second group (comparison group 1, n=30) additionally underwent a course of supravenous laser irradiation of blood. In the third group (comparison group 2, n=30), broadband medium-wave phototherapy was performed against the background of basic therapy. Patients of the fourth group (main group, n=30) in addition to basic therapy received a course of combined exposure to supravenous laser blood irradiation and phototherapy. The concentrations of adrenocorticotropin, cortisol and beta-endorphin were determined in the blood of patients twice (before the start of treatment and 1 month after the start of therapy) using ELISA. The clinical condition of patients in the groups was assessed by changes in the EASI index. Additionally, we studied the dynamics of the level of reactive and personal anxiety using the Spielberger–Khanin questionnaire. RESULTS: Positive dynamics of adrenocorticotropin, cortisol and beta-endorphin were noted only in the comparison groups and the main group, which proves the high efficiency of correction of the neurohumoral status of patients through a course of complex use of supravenous laser blood irradiation and broadband mid-wave phototherapy. Quantitative changes in the assessed parameters during complex therapy with therapeutic physical factors indicate a supra-additive version of their interaction, realized through different modalities, points of application and mechanisms for realizing the biological potential of physiotherapeutic effects. CONCLUSION: The results obtained convincingly prove the effectiveness of an additional course of use of supravenous laser irradiation of blood in combination with broadband medium-wave phototherapy when correcting the neuroendocrine status in patients with true eczema. The close correlation between neurohumoral indicators and clinical and psychological patterns of the disease proves the pathogenetic significance of the studied neuroendocrine indicators, which allows us to consider their dynamics as informative criteria for the effectiveness of the treatment.

Anomalies of Midbrain/Hindbrain Development: Malformations of Cerebellum: Diagnosis, Classification, and Rehabilitative Hypothesis

AbstractExtensive research has been conducted on the cerebellum, making it one of the most thoroughly investigated regions of the brain. It plays a fundamental role not only in motor control but also in motor learning and cognition. The development of the cerebellum is a lengthy process, beginning during the embryonic period up to the first years of life. This slow and protracted process makes it a vulnerable organ liable to different insults, responsible for many developmental disorders such as Dandy–Walker syndrome, medulloblastoma, dystroglicanopathy, pontocerebellar hypoplasia, thubulinopathies, and Jubert syndrome. Due to several factors, the true prevalence of cerebellar malformations is not known in most cases. The cerebellum undergoes development through following four fundamental stages:(1) Identification of the cerebellar region at the boundary between the midbrain and hindbrain.(2) Establishment of two cell proliferation compartments: firstly, Purkinje cells and deep cerebellar nuclei emerge from the ventricular zone of the metencephalic alar plate; secondly, granule cell precursors are generated from a separate proliferation compartment known as the upper rhombic lip.(3) Migration of granule cells toward the interior: granule precursor cells constitute the external granular layer (EGL), and during the initial postnatal year, granule cells migrate inward to their final position in the internal granular layer.(4) Formation of cerebellar circuitry and subsequent differentiation.Based on different types of involvement of the structures detected in the brain magnetic resonance, the classification of brainstem and cerebellar anomalies is divided into three categories: (1) mainly the cerebellum, (2) mainly the brain stem, and (3) both involved. This review will outline the developmental processes of the cerebellum and delve into common developmental disorders associated with it, including the Dandy–Walker syndrome, cerebellar hypoplasia, rhomboencephalosynapsis, lissencephaly, and gray matter heterotopias.

Surgical Management and Short-Term Outcome of Patients with Posterior Fossa Tumor in All Age Groups: Our Perspective

Background: Different types of brain tumor can occur in the region of posterior fossa. Ependymoma, medulloblastoma and pilocytic astrocytoma occur mostly in children and rarely in adults. Brain metastases in adults are the most common malignancies at this site. Other tumors that occur in the posterior fossa are meningioma, schwannoma, hemangioblastoma, brain stem glioma and epidermoid tumors. Posterior fossa tumor has different treatment approaches and prognosis. So, an accurate diagnosis, surgical approaches, complication analysis and outcome assessment are mandatory. Objective: To evaluate the clinical aspects, surgical approach, role of preoperative shunt, post-operative complications, and short-term outcome of patients with posterior fossa tumor in different age groups. Methods: This cross-sectional observational study included 36 patients with posterior fossa tumors that were admitted and operated in the Neurosurgery Department of Rangpur Medical College Hospital between the period of November 2018 and June 2022. In each patient clinically diagnosis was confirmed by MRI of Brain with contrast followed by histopathology. Results: Out of 36 patients, 23(63.9%) patients were male and 13(36.1%) were female. Mean age was 18.01±13.95 SD years (minimum 6 months and maximum 45 years), more common in pediatric age group (36.1% <10 years and 25% between 11-20 years). Common presentations were headache (91.6%), vomiting (83.3%) and ataxia (72.2%). Medulloblastoma (27.8%) and ependymoma (25%) were common histological types. Surgical outcome was excellent in 17 cases (47.2%), while poor in 5.6% and 19.4% patients died. There was no statistically significant association of surgical outcome with age (p=0.148) and sex (p=0.170). Suboccipital craniotomy was superior to other surgical procedures in terms of patient’s outcome (p=0.031). Ependymomas and Astrocytomas had better outcome (p=0.014). Conclusions: Surgical outcome is related to the operative approach and histology of the tumor in this study, but no significant association of patient’s outcome with age, sex and preoperative procedure. J Rang Med Col. March 2024; Vol. 9, No. 1: 3-9

Blood brain barrier disruption and glutamatergic excitotoxicity in post-acute sequelae of SARS COV-2 infection cognitive impairment: potential biomarkers and a window into pathogenesis.

To investigate the association between blood-brain barrier permeability, brain metabolites, microstructural integrity of the white matter, and cognitive impairment (CI) in post-acute sequelae of SARS-COV-2 infection (PASC). In this multimodal longitudinal MRI study 14 PASC participants with CI and 10 healthy controls were enrolled. All completed investigations at 3 months following acute infection (3 months ± 2 weeks SD), and 10 PASC participants completed at 12 months ± 2.22 SD weeks. The assessments included a standard neurological assessment, a cognitive screen using the brief CogState battery and multi-modal MRI derived metrics from Dynamic contrast enhanced (DCE) perfusion Imaging, Diffusion Tensor Imaging (DTI), and single voxel proton Magnetic Resonance Spectroscopy. These measures were compared between patients and controls and correlated with cognitive scores. At baseline, and relative to controls, PASC participants had higher K-Trans and Myo-inositol, and lower levels of Glutamate/Glutamine in the frontal white matter (FWM) (p < 0.01) as well as in brain stem (p < 0.05), and higher FA and lower MD in the FWM (p < 0.05). In PASC participants, FA and MD decreased in the FWM at 12 months compared to baseline (p < 0.05). K-Trans and metabolite concentrations did not change significantly over time. Neurocognitive scores did not correlation with the increased permeability (K trans). PASC with CI is associated with BBB impairment, loss of WM integrity, and inflammation at 3 months which significantly but not uniformly improved at 12 months. The loss of WM integrity is possibly mediated by BBB impairment and associated glutamatergic excitotoxicity.

Comparative study of virus and lymphocyte distribution with clinical data suggests early high dose immunosuppression as potential key factor for the therapy of patients with BoDV-1 infection

ABSTRACT Borna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies. ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1act: general activation of microglial cells; Iba1nod: formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; patearly: patients treated with early high dose steroid shot; patlate: patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum

Brain death diagnostics: use of ancillary tests

AbstractWith the determination of the definitive, irreversible loss of the overall function of the cerebrum, cerebellum and brain stem (irreversible loss of brain function, IHA, "brain death"), the death of the human being is determined from a scientific-medical point of view. The determination of IHA, with cardiovascular function being maintained by intensive care, requires special diagnostics ("brain death diagnostics"). This is carried out in the intensive care unit either to assess the medical prognosis, or as a prerequisite for post-mortem organ donation. In Germany, in accordance with the Transplantation Act, the procedural rules for determining IHA are laid down in corresponding guidelines of the German Medical Association (RL-BÄK), the 5th update of which has been in force since September 2022. Here, the indications, the requirements and the technical procedures of ancillary tests (electroencephalography, early auditory and somatosensory evoked potentials, Doppler and duplex sonography, computed tomography angiography, radionuclide perfusion scintigraphy, digital subtraction angiography) according to the German guidelines are outlined.