Intratumoral histological and molecular heterogeneity in an adult diffuse glioma.

Adult-type diffuse gliomas are the most prevalent type of malignant adult brain tumors. Intratumoral heterogeneity can hinder accurate diagnosis and subsequent treatment. This case report documents a tumor with intratumoral heterogeneity, both histologically and by methylation analysis, located within the left cerebral hemisphere of a 29-year-old female. She presented after a witnessed generalized tonic clonic seizure at home. Two years prior she had a witnessed seizure; however, no brain imaging was done at the time. Magnetic resonance imaging (MRI), on this admission, showed a mass lesion in the left frontal operculum with poorly identified margins and right-sided midline shift. Sampling from the left temporal lobe showed an IDH-mutant, ATRX-mutant astrocytoma, which appeared grade 4 in the enhancing anterior portion and grade 2 in the left temporal lobe. Methylation analysis confirmed this heterogeneity. In summary, this is an excellent example of tumor heterogeneity both histologically and by molecular analysis. It is probable, given the clinical history of presentation 2 years prior, that this tumor originated as a low-grade glioma and subsequently evolved.

Brain biopsy in neurological disease of unknown etiology: A single-center 12-year retrospective analysis.

There are no international guidelines for brain biopsy in neurological disease of unknown etiology, yet most practicing neurologists will encounter difficult cases in which biopsy is considered. This patient cohort is heterogenous, and it is unclear in which circumstances biopsy is most useful. We performed an audit of brain biopsies reviewed in our neuropathology department from 2010 to 2021. Of 9,488 biopsies, 331 biopsies undertaken for an undiagnosed neurological disease were identified. Where documented, the commonest symptoms were hemorrhage, encephalopathy, and dementia. 29% of biopsies were non-diagnostic. The most common clinically relevant findings on biopsy were infection, cerebral amyloid angiopathy with or without angiitis, and demyelination. Rarer conditions included CNS vasculitis, non-infectious encephalitis, and Creutzfeldt Jakob Disease. We highlight the value of brain biopsy in the workup of cryptogenic neurological disease despite recent advances in less invasive diagnostics.

Intracranial haemorrhage and falls: cause or effect?

INTRODUCTION: A difficult question in autopsy practice is whether intracranial haemorrhage has resulted from or brought about a fall. MATERIAL AND METHODS: To address this we undertook a retrospective study of all autopsy reports (N = 2126) complied over a 10 year period (2009-2018). Of 720 patients who underwent a comprehensive post mortem neuropathologic examination we found 226 patients who had a history of a fall. RESULTS: Of the 226 with a history of fall, 175 (79%) had an intracranial haemorrhage which was classified as truamatic (n = 134, 77%) or spontaneous (n = 41, 23%. Within the traumatic group, falls from a standing height (51%) were more common than falls involving stairs (31%) or falls from a height (12%). Cerebral contusional injury (51%) and subdural haemorrhage (45%) were the most common type of haemorrhage in the traumatic group. In the spontaneous haemorrhage group cerebral amyloid angiopathy (49%) was the commonest detected cause and was typically lobar in distribution). CONCLUSION: We are of the view that a comprehensive analysis of fatal falls with intracranial haemorrhage warrants a detailed neuropathologic examination as part of the overall death analysis.

Stability of Extemporaneously Compounded Nadolol 10-mg/mL Suspension in Oral Mix in Glass and Plastic Bottles and Plastic Syringes.

An oral liquid formulation of nadolol, which is required for administration to patients who cannot swallow intact tablets, is not commercially available. The objective of this study was to evaluate the stability of nadolol 10 mg/mL prepared in Oral Mix vehicle and stored in amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride for 91 days at 4ÆC and 25ÆC; and polypropylene oral plastic syringes at 25ÆC only. Three separate batches of nadolol suspension 10 mg/mL were prepared with Oral Mix. Of the suspension, 50-mL aliquots were stored in 100-mL bottles (amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride). Half of the bottles from each container type were stored at 25ÆC and the other half at 4ÆC. On study days 0, 2, 7, 14, 21, 28, 42, 56, 72, and 91, nadolol concentration was determined using a reverse-phase, stability-indicating liquid chromatographic method from samples drawn from each type of container at each temperature. Oral syringes (3 mL), filled with 2 mL of suspension, were stored at 25ÆC and tested on days 0, 2, 7, 21, 42, and 91. The concentration of nadolol 10 mg/mL in Oral Mix in all study samples from bottles and oral syringes remained within 3.5% of the initial concentration. Based on the fastest degradation rate with 95% confidence, on day 91, between 99% to 100% and 98% to 100% remained in suspensions stored in bottles at 25ÆC and 4ÆC, respectively. Oral syringes at 25ÆC had 94% remaining on day 91. Multiple linear regression analysis demonstrated that the percent remaining was related to study day and container, but not temperature. On day 91, nadolol 10 mg/mL oral suspensions prepared with Oral Mix and stored in all bottle types at 4ÆC will retain more than 98% of the initial concentration compared to 99% at 25ÆC and only 94% when stored in oral syringes.

Impact of the 2016 World Health Organization Classification of Tumours of the Central Nervous System: an Irish experience.

The 2016 World Health Organization Classification of Tumours of the Central Nervous System Tumours represents the most significant update to neuro-oncological tumour classification to date, compared with previous updates. This update reflects the substantial advances in molecular and genetic understanding of both adult and childhood brain tumours which have occurred in recent years. These advances have meant that an increasing array of molecular tests are required to definitively classify a tumour, allowing for a more precise integrated pathological diagnosis, but at the expense of a more challenging pathology workup. We review the changes incorporated into the 2016 classification and describe the impact of these changes in an Irish neuropathology laboratory.