Ultra-fast deep-learned CNS tumour classification during surgery.

Central nervous system tumours represent one of the most lethal cancer types, particularly among children1. Primary treatment includes neurosurgical resection of the tumour, in which a delicate balance must be struck between maximizing the extent of resection and minimizing risk of neurological damage and comorbidity2,3. However, surgeons have limited knowledge of the precise tumour type prior to surgery. Current standard practice relies on preoperative imaging and intraoperative histological analysis, but these are not always conclusive and occasionally wrong. Using rapid nanopore sequencing, a sparse methylation profile can be obtained during surgery4. Here we developed Sturgeon, a patient-agnostic transfer-learned neural network, to enable molecular subclassification of central nervous system tumours based on such sparse profiles. Sturgeon delivered an accurate diagnosis within 40 minutes after starting sequencing in 45 out of 50 retrospectively sequenced samples (abstaining from diagnosis of the other 5 samples). Furthermore, we demonstrated its applicability in real time during 25 surgeries, achieving a diagnostic turnaround time of less than 90 min. Of these, 18 (72%) diagnoses were correct and 7 did not reach the required confidence threshold. We conclude that machine-learned diagnosis based on low-cost intraoperative sequencing can assist neurosurgical decision-making, potentially preventing neurological comorbidity and avoiding additional surgeries.

Actinomycosis of the abdominal wall after cholecystectomy: transferral theory.

Abdominal actinomycosis is a rare disease caused by Gram-positive anaerobic Actinomyces bacteria. Here, we present a patient with an intrauterine contraceptive device who developed a long lasting and unexplained recurrent, painful abdominal swelling a few months after a laparoscopic cholecystectomy.

Postmortem verification of MS cortical lesion detection with 3D DIR.

OBJECTIVE: To assess the sensitivity and specificity of 3D double inversion recovery (DIR) MRI for detecting multiple sclerosis (MS) cortical lesions (CLs) using a direct postmortem MRI to histopathology comparison. METHODS: Single-slab 3D DIR and 3D fluid-attenuated inversion recovery (FLAIR) images of 56 matched fresh brain samples from 14 patients with chronic MS were acquired at 1.5 T. The images of both sequences were prospectively scored for CLs in consensus by 3 experienced raters who were blinded to histopathology and clinical data. Next, CLs were identified histopathologically and were scored again on 3D DIR and 3D FLAIR (retrospective scoring). CLs were classified as intracortical or mixed gray matter (GM)-white matter lesions. Deep GM lesions were also scored. False-positive scores were noted and, from this, specificity was calculated. RESULTS: We found a sensitivity for 3D DIR to detect MS CLs of 18%, which is 1.6-fold higher than 3D FLAIR (improves to 37% with retrospective scoring; 2.0-fold higher than 3D FLAIR). We detected mixed GM-white matter lesions with a sensitivity of 83% using 3D DIR (65% sensitivity for 3D FLAIR), which improved to 96% upon retrospective scoring (91% for 3D FLAIR). For purely intracortical lesions, 3D DIR detected more than 2-fold more than 3D FLAIR (improved to >3-fold upon retrospective scoring). The specificity of 3D DIR to MS CLs was found to be 90%. CONCLUSIONS: In this postmortem verification study, we have shown that 3D DIR is highly pathologically specific, and more sensitive to CLs than 3D FLAIR in MS.

Abundant extracellular myelin in the meninges of patients with multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS) myelin debris has been observed within MS lesions, in cerebrospinal fluid and cervical lymph nodes, but the route of myelin transport out of the brain is unknown. Drainage of interstitial fluid from the brain parenchyma involves the perivascular spaces and leptomeninges, but the presence of myelin debris in these compartments has not been described. AIMS: To determine whether myelin products are present in the meninges and perivascular spaces of MS patients. METHODS: Formalin-fixed brain tissue containing meninges from 29 MS patients, 9 non-neurological controls, 6 Alzheimer's disease, 5 stroke, 5 meningitis and 7 leucodystrophy patients was investigated, and immunohistochemically stained for several myelin proteins [proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)]. On brain material from MS patients and (non)neurological controls, PLP immunostaining was used to systematically investigate the presence of myelin debris in the meninges, using a semiquantitative scale. RESULTS: Extensive extracellular presence of myelin particles, positive for PLP, MBP, MOG and CNPase in the leptomeninges of MS patients, was observed. Myelin particles were also observed in perivascular spaces of MS patients. Immunohistochemical double-labelling for macrophage and dendritic cell markers and PLP confirmed that the vast majority of myelin particles were located extracellularly. Extracellular myelin particles were virtually absent in meningeal tissue of non-neurological controls, Alzheimer's disease, stroke, meningitis and leucodystrophy cases. CONCLUSIONS: In MS leptomeninges and perivascular spaces, abundant extracellular myelin can be found, whereas this is not the case for controls and other neurological disease. This may be relevant for understanding sustained immunogenicity or, alternatively, tolerogenicity in MS.

Translating pathology in multiple sclerosis: the combination of postmortem imaging, histopathology and clinical findings.

BACKGROUND: Studies combining postmortem magnetic resonance imaging (MRI) and histopathology have provided important insights into the abnormalities reflected by MRI. MATERIALS AND METHODS: A short overview of these studies applied to multiple sclerosis (MS) is provided in this review, and the Amsterdam postmortem imaging protocol is specifically highlighted. CONCLUSION: Postmortem MRI and histopathology correlation studies have enabled a direct translation of basic pathology in MS to the clinical setting, and have simultaneously served as a biological validation of new MRI techniques.