Progesterone as a Neuroprotective Agent in Neonatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review.

Hypoxic-ischaemic encephalopathy (HIE) in the newborn baby is a major contributor to neonatal mortality and morbidity across the world. Therapeutic hypothermia (TH) is the current standard treatment for moderate to severe HIE, but not all babies benefit. Potential neuroprotective actions of progesterone (PROG) include anti-apoptotic, anti-inflammatory, and anti-oxidative effects and reduction of energy depletion, tissue/cellular oedema, and excitotoxicity. In pre-clinical studies of neonatal HIE, PROG has neuroprotective properties but has not been the subject of systematic review. Here, our objective was to evaluate the evidence base for PROG as a potential therapeutic agent in HIE. The PICO framework was used to define the following inclusion criteria. Population: human neonates with HIE/animal models of HIE; intervention: PROG +/- other agents; comparison: V.S. control; outcome: pathological, neurobehavioural, and mechanistic outcome measures. Medline, EMBASE, and CINHAL were then searched between August to October 2018 using pre-defined medical subject heading and keywords. Study inclusion, data extraction, and risk of bias (ROB) analysis using the SYRCLE ROB tool were carried out by two authors. 14 studies were included in the review. They typically displayed a high ROB. This systematic review suggests that PROG reduced neuropathology and reduced neurobehavioural deficits post-hypoxic-ischaemic (HI) insult in 8 and 3 studies, respectively. However, there was sex dimorphism in the effects of PROG. In addition, there are limitations and biases in these studies, and there remains a need for well-designed large pre-clinical studies with greater methodological quality to further inform the efficacy, safety, dose, timing, and frequency of PROG administration. With such data, large animal studies could be planned combining PROG administration with and without TH.

Do animal models of brain tumors replicate human peritumoral edema? a systematic literature search.

INTRODUCTION: Brain tumors cause morbidity and mortality in part through peritumoral brain edema. The current main treatment for peritumoral brain edema are corticosteroids. Due to the increased recognition of their side-effect profile, there is growing interest in finding alternatives to steroids but there is little formal study of animal models of peritumoral brain edema. This study aims to summarize the available literature. METHODS: A systematic search was undertaken of 5 literature databases (Medline, Embase, CINAHL, PubMed and the Cochrane Library). The generic strategy was to search for various terms associated with "brain tumors", "brain edema" and "animal models". RESULTS: We identified 603 reports, of which 112 were identified as relevant for full text analysis that studied 114 peritumoral brain edema animal models. We found significant heterogeneity in the species and strain of tumor-bearing animals, tumor implantation method and edema assessment. Most models did not produce appreciable brain edema and did not test for observable manifestations thereof. CONCLUSION: No animal model currently exists that enable the investigation of novel candidates for the treatment of peritumoral brain edema. With current interest in alternative treatments for peritumoral brain edema, there is an unmet need for clinically relevant animal models.

Giant spinal nerve sheath tumours - Surgical challenges: case series and literature review.

Background: Giant nerve sheath tumours (GNST) are rare and literature on their management is scant. Spinal GNST present as a surgical challenge due to the involvement of anatomical regions often outside the "comfort zone" of a spinal surgeon. This case series aims to identify challenges in the surgical management of GNSTs. Methods: Retrospective case note review of all spinal GNST cases from 2010 to 2016 managed in Sheffield Teaching Hospitals identified 8 patients, 3 of whom were incidental findings (kept under surveillance) and were excluded. 5 cases were treated surgically. Data collected included patient demographic, presenting symptom(s), radiological data, surgical approach to the tumour and challenges encountered, histopathology report and follow up. Results: Our cohort consisted entirely of females (N = 5) with a mean age of 56.4 years (range 45-70). Imaging studies and histopathological diagnoses confirmed 5 GNSTs (four benign schwannomas and one ganglioneuroma). A Single-stage anterior approach was adopted for three patients while a combined anterior-posterior approach was adopted for the remaining two. In one patient, a posterior approach was initially planned, but this was abandoned and converted to an anterior approach following onset of acute superior vena cava (SVC) syndrome secondary to SVC compression by the giant tumour on prone positioning of the patient. PET imaging of case 3 showed intense tracer uptake consistent with malignancy, however histology confirmed WHO grade 1 Schwannoma. The other three non-operated GNSTs are kept under yearly radiological and clinical surveillance. Conclusions: GNSTs are surgically challenging as they often invade territories that are beyond the comfort zone of one single specialty. A multidisciplinary approach with careful pre-operative surgical planning is recommended. Patients in whom a posterior approach is planned should have a trial of prone positioning pre-operatively. Careful interpretation of FDG-PET imaging is recommended due to the possibility of false positive result.

Imaging Spectrum of the Developing Glioblastoma: A Cross-Sectional Observation Study.

Glioblastoma (GBM) has the typical radiological appearance (TRA) of a centrally necrotic, peripherally enhancing tumor with surrounding edema. The objective of this study was to determine whether the developing GBM displays a spectrum of imaging changes detectable on routine clinical imaging prior to TRA GBM. Patients with pre-operative imaging diagnosed with GBM (1 January 2014-31 March 2022) were identified from a neuroscience center. The imaging was reviewed by an experienced neuroradiologist. Imaging patterns preceding TRA GBM were analyzed. A total of 76 out of 555 (14%) patients had imaging preceding TRA GBM, 57 had solitary lesions, and 19 had multiple lesions (total = 84 lesions). Here, 83% of the lesions had cortical or cortical/subcortical locations. The earliest imaging features for 84 lesions were T2 hyperintensity/CT low density (n = 18), CT hyperdensity (n = 51), and T2 iso-intensity (n = 15). Lesions initially showing T2 hyperintensity/CT low density later showed T2 iso-intensity. When CT and MRI were available, all CT hyperdense lesions showed T2 iso-intensity, reduced diffusivity, and the following enhancement patterns: nodular 35%, solid 29%, none 26%, and patchy peripheral 10%. The mean time to develop TRA GBM from T2 hyperintensity was 140 days and from CT hyperdensity was 69 days. This research suggests that the developing GBM shows a spectrum of imaging features, progressing through T2 hyperintensity to CT hyperdensity, T2 iso-intensity, reduced diffusivity, and variable enhancement to TRA GBM. Red flags for non-TRA GBM lesions are cortical/subcortical CT hyperdense/T2 iso-intense/low ADC. Future research correlating this imaging spectrum with pathophysiology may provide insight into GBM growth patterns.

An unusual headache: CSF negative APML relapse in the brain.

Acute Promyelocytic Leukaemia (APML) is a subtype of Acute Myeloid Leukaemia (AML), responsible for around 10% of cases of the disease in adults. Extra medullary disease (EMD) occurs infrequently in APML, but where EMD does occur, the central nervous system is one of the most commonly infiltrated sites. Our case describes a man in his 40s undergoing post-therapy surveillance for APML who presented to follow-up clinic with a headache, which was ultimately found to be caused by a tumour comprised of APML cells. His case presented a diagnostic challenge due to the benign appearances of the lesion on initial computed tomography brain imaging and the non-diagnostic cerebrospinal fluid analysis. The diagnostic difficulties described in our case emphasizes that clinicians working with APML patients must approach new neurological symptoms with a high degree of suspicion to prevent diagnostic delay.

Spontaneous regression of retro-odontoid post traumatic cicatrix following occipitocervical fixation.

This case report describes a patient who presented with myelopathy secondary to a large retro-odontoid post traumatic cicatrix. The objective of this study was to discuss the clinical presentation, pathogenesis, imaging, and surgical management of pseudoarthrosis tissue mass associated with odontoid nonunion. Atlantoaxial subluxation (AAS) has been widely reported in patients with rheumatoid arthritis. AAS leads to repeated cycles of partial tear and repair of ligaments around the altantoaxial complex, resulting in the formation of periodontoid mass (pseudotumor). It is thought that formation of retro-odontoid post traumatic mass (cicatrix), in certain cases of odontoid fracture, is because of similar pathology. This is a retrospective review of case note. Here, the patient underwent posterior decompression through a C1-C2 laminectomy and occipitocervical (C0-C4) fusion with instrumentation, which resulted in dramatic improvement in his symptoms and spontaneous regression of retro-odontoid post traumatic cicatrix. We have described an interesting and a rare case of a large pseudoarthrosis tissue mass associated with odontoid nonunion, which regressed following stand-alone posterior instrumentation. To the best of our knowledge, only a handful of such cases of spontaneous regression of retro-odontoid post traumatic cicatrix following occipitocervical fixation have been described in literature, and our case adds to the growing list of such cases and may help in understanding the natural history of the disease process one day. Although rare, post traumatic cicatrix should be considered as a differential diagnosis of enhancing retro-odontoid mass, especially if there is any history of cervical spine trauma.

Spontaneous resolution of symptomatic lumbar synovial cyst.

Lumbar synovial cyst arises from the facet joint and can lead to back pain, radiculopathy, neurogenic claudication or even cauda equina syndrome. Although most surgeons would consider surgery to be the treatment of choice, the natural history of the disease process remains unknown and uncertainty still exists regarding optimal management of this controversial entity. We illustrate a case of large L5/S1 synovial cyst for which surgery was initially planned. However, it resolved spontaneously without any treatment. We also provide a brief literature review regarding conservative, surgical and minimally invasive management of symptomatic lumbar synovial cyst with special reference to patient outcome.