A case of conservatively managed idiopathic spinal cord herniation presenting with low-pressure headache.

Idiopathic spinal cord herniation presenting with low-pressure headache is extremely rare. We present a case of thoracic ventral spinal cord herniation in a 35-year-old lady who presented with low-pressure headaches. To our knowledge, this is only the fourth case described in the literature of spontaneous ventral cord herniation presenting in this way. The patient was managed conservatively with no manifestation of focal neurological symptoms at 12-month follow-up. The proposed aetiology of spontaneous ventral cord herniation is an initial CSF leak via a dural defect, through which the cord subsequently also enters blocking the CSF leak. We endorse a conservative approach for patients who present similarly, secondary to the above pathophysiology.

Intra-arterial lidocaine therapy via the middle meningeal artery for migraine headache: Theory, current practice and future directions.

Recent developments in neurointerventional research have seen the emergence of the middle meningeal artery (MMA) as an effective conduit for intra-arterial (IA) therapy for a number of pathologies. Here, we review the anatomical, pathophysiological and experimental basis for utilisation of the MMA for IA treatment of migraine headache. We explore the in-human case literature for the treatment of headaches with IA lidocaine and discuss considerations and challenges for future research.

Comparison of External Ventricular Drains with Ventricular Access Devices for the Emergency Management of Adult Hydrocephalus.

OBJECTIVE: We compared external ventricular drains (EVDs) with percutaneous continuous cerebrospinal fluid (CSF) drainage via ventricular access devices (VADs) for the acute management of hydrocephalus in adults. METHODS: This was a retrospective review of all ventricular drains inserted for a new diagnosis of hydrocephalus into noninfected CSF over four years. We compared infection rates, return to theatre, and patient outcome between EVDs and VADs. We explored the effect of duration of drainage, frequency of sampling, hydrocephalus aetiology, and catheter location on these outcomes using multivariable logistic regression modelling. RESULTS: We included 179 drains (76 EVDs and 103 VADs). EVDs were associated with a higher rate of unplanned return to theatre for replacement or revision (27/76, 36%, vs. 4/103, 4%, OR: 13.4 95%CI: 4.3-55.8). However, infection rates were higher in VADs (13/103, 13% vs. 5/76, 7%, OR: 2.0, 95%CI: 0.65-7.7). EVDs were 91% antibiotic impregnated whereas VADs were 98% nonimpregnated. In multivariable analysis, infection was associated with duration of drainage (median: 11 days prior to infection for infected drains vs. 7 days total for noninfected drains), but not drain type (VADs vs. EVDs OR: 1.6, 95%CI: 0.5-6). CONCLUSIONS: EVDs had a higher rate of unplanned revisions but a lower infection rate compared to VADs. However, in multivariable analysis choice of drain type was not associated with infection. We suggest a prospective comparison of antibiotic impregnated VADs and EVDs using similar sampling protocols to assess whether VADs or EVDs for acute hydrocephalus have a lower overall complication rate.

Promoting padawans: a survey examining the state of mentorship in neurosurgical training in the United Kingdom.

BACKGROUND: Mentorship has long since been acknowledged as an integral part of Neurosurgical training. The authors sought to evaluate the state of mentorship in Neurosurgical training in the United Kingdom (UK). METHODS: A 28-point questionnaire was sent to all neurosurgical trainees in the UK and Ireland via the British Neurosurgical Trainee's Association (BNTA), comprising 180 trainees. RESULTS: There were 75 responses (180 trainees on the mailing list, 42% response rate). Despite all respondents reporting it to be at least somewhat important to have a mentor, 16% felt they had no mentors. The mean number of mentors was 2.91 with 72% of respondents having more than 1 mentor. In terms of the content of mentorship relationships, 63% were comfortable discussing career related topics with their mentor to a high or very high degree but only 29% felt comfortable discussing their general wellbeing. With regards to allocated educational supervisors, 43% thought this person to be a 'low' or 'very low' source of mentorship. The three most important traits of the ideal mentor as reported by respondents were: someone chosen by them (48%), working in the same hospital (44%) and having received formal mentorship training (36%). CONCLUSIONS: The current perception of mentorship in Neurosurgery from the surveyed trainees is mixed. A healthy majority of trainees benefit from mentorship of some kind, whilst a significant minority feel underserved. The surveyed trainees feel mentorship is slanted more towards clinical and professional aspects of development than it is towards personal ones. Suggestions for future insight would be an evaluation of senior registrar and consultant sentiments towards mentorship, whilst exploration into more flexible models for establishing mentoring relationships may help to address the heavy importance of trainee choice which is voiced by this survey's results.

What is the quality of the information available on the internet for patients suffering with sciatica?

BACKGROUND: Sciatica is a common neurological condition with a wide variety of clinical specialists and allied health professionals involved, and a broad range of treatment options. We sought to assess the quality of information available on the internet. METHODS: An internet search for 'sciatica' was performed using 'Google'. The first fifty links were assessed using the DISCERN instrument, a validated questionnaire for health consumers and providers. RESULTS: After exclusions, 44 websites were assessed. Only 37% of sites had clear aims and objectives; 79% provided relevant information; 81% did not provide clear sources of their information; 67% had no indication of when the information was compiled or updated; 63% clarified that more than one treatment option was available; only 28% described in moderate to extensive detail how the various treatment modalities might work; only 14% informed patients of potential risks and complications for each treatment. The biased and/or unbalanced websites amounted to 40%, offering greater detail about one treatment modality over others. Overall, 93% of assessed websites did not inform patients of the consequences/natural history if no treatment were undertaken; and 91% did not describe the potential impact of treatment and how it could affect quality of life. CONCLUSIONS: Despite the role that the internet plays in everyday life, information on the common and debilitating condition of sciatica is mostly of low-to-moderate quality, and with serious shortcomings. Healthcare stakeholders ought to be aware of the risks of misinformation and ensure that health-related internet website design and upkeep is guided by instruments such as DISCERN.

Management of traumatic atlanto-occipital dislocation in a 10-year-old with noninvasive halo immobilization: A case report.

Background: Traumatic atlanto-occipital dislocation is an unstable injury of the craniocervical junction. For pediatric patients, surgical arthrodesis of the occipitocervical junction is the recommended management. While having a high success rate for stabilization, the fusion comes with obvious morbidity of limitation in cervical spine flexion, extension, and rotation. An alternative is external immobilization with a conventional halo. Case Description: We describe the case of a 10-year-old boy who was treated successfully for traumatic AOD with a noninvasive pinless halo. Following initial brain trauma management, we immobilized the craniocervical junction with a pinless halo after reducing the atlanto-occipital dislocation. The pinless halo was kept on at all times for the next 3 months. The craniocervical junction alignment was monitored with weekly cervical spine X-rays and CT craniocervical junction on day 15th, day 30th, and day 70th. A follow-up MRI C-spine 3 months from presentation confirmed resolution of the soft-tissue injury and the pinless halo was removed. Dynamic cervical spine X-rays revealed satisfactory alignment in both flexion and extension views. The patient has been followed up for 2 years postinjury and no issues were identified. Conclusion: Noninvasive pinless halo is a potential treatment option for traumatic pediatric atlanto-occipital dislocation. This should be considered bearing in mind multiple factors including age and weight of the patient, severity of the atlanto-occipital dislocation (Grade I vs. Grade II and incomplete vs. complete), concomitant skull and scalp injury, and patient's ability to tolerate the halo. It is vital to emphasize that this necessitates close clinicoradiological monitoring.

Micro-Meta App: an interactive tool for collecting microscopy metadata based on community specifications.

For quality, interpretation, reproducibility and sharing value, microscopy images should be accompanied by detailed descriptions of the conditions that were used to produce them. Micro-Meta App is an intuitive, highly interoperable, open-source software tool that was developed in the context of the 4D Nucleome (4DN) consortium and is designed to facilitate the extraction and collection of relevant microscopy metadata as specified by the recent 4DN-BINA-OME tiered-system of Microscopy Metadata specifications. In addition to substantially lowering the burden of quality assurance, the visual nature of Micro-Meta App makes it particularly suited for training purposes.

Adult WHO grade II ependymomas: is Ki67 a sex-specific proliferation marker?

Ki67 is a marker for proliferation of a given cell population. Low expression of Ki67 may be associated with a favourable outcome. We investigate how the proliferation index correlates with the location, morphology and behaviour of WHO grade II ependymomas with a single-centre cohort study of adult patients admitted for surgery of WHO grade II ependymomas between 2008 and 2018. Seventeen patients were included, seven had supratentorial and 10 had infratentorial tumours. Three patients died and eight had recurrent disease. Age, gender, location, extent of resection, chemotherapy, radiotherapy and histological markers were not associated with tumour progression. Both unadjusted and adjusted analysis confirmed a higher Ki67 index in male patients. Sensitivity analysis further supported the correlation between Ki67 and male gender. Ki67 may be sex specific but does not seem to correlate with survival and time to recurrence in this series.

Burnout amongst neurosurgical trainees in the UK and Ireland.

INTRODUCTION: Burnout is becoming an increasingly recognised phenomenon within the medical profession. This study aims to investigate the presence of burnout amongst neurosurgical trainees in the UK and Ireland as well as investigating potential exacerbating and protective factors. METHOD: An online survey was sent to all neurosurgical trainees in the UK and Ireland via the British Neurosurgical Trainees' Association (BNTA) mailing list. Responding participants anonymously completed the Copenhagen Burnout Inventory (CBI) and answered questions about known risk factors for burnout including workplace environment, workplace bullying, time spent on leisure activities and sleep and reported likelihood of leaving neurosurgery. We also collated data on responders' demographics. We compared CBI scores for participants with and without risk factors to determine correlation with CBI. RESULTS: There were 75 respondents (response rate 42%) from a range of ages and all training grades, 72% of whom were male. The median CBI score was 38.85 (IQR 17.76). Participants showed a higher degree of personal and workplace burnout (median CBIs of 47.02, IQR 25.00; and 49.14, IQR 19.64, respectively) compared with patient-related burnout (median CBI 18.67, IQR 25.00). Participants with the following self-reported risk factors were significantly more likely to have higher CBIs: workplace bullying (p = 0.01), getting on less well with colleagues (p < 0.05), working longer hours (p < 0.05) and insufficient sleep, exercise and leisure time (all p < 0.01). Those with higher CBI scores were more likely to consider leaving neurosurgical training (p = 0.01). CONCLUSION: We identified a high burnout incidence in a cohort representative of UK neurosurgical trainees, although our results may have been skewed somewhat by selection bias. We determined potential risk factors for burnout related to specific workplace stressors and time for non-work activities. In the future, changes to training curricula should address these issues, aiming to improve training, enhance patient care and reduce attrition rates.

Acute bilateral foot drop with or without cauda equina syndrome-a case series.

INTRODUCTION: Isolated acute bilateral foot drop due to degenerative spine disease is an extremely rare neurosurgical presentation, whilst the literature is rich with accounts of chronic bilateral foot drop occurring as a sequela of systemic illnesses. We present, to our knowledge, the largest case series of acute bilateral foot drop, with trauma and relevant systemic illness excluded. METHODS: Data from three different centres had been collected at the time of historic treatment, and records were subsequently reviewed retrospectively, documenting the clinical presentation, radiological level of compression, timing of surgery, and degree of neurological recovery. RESULTS: Seven patients are presented. The mean age at presentation was 52.1 years (range 41-66). All patients but one were male. All had a painful radiculopathic presentation. Relevant discopathy was observed from L2/3 to L5/S1, the commonest level being L3/4. Five were treated within 24 h of presentation, and two within 48 h. Three had concomitant cauda equina syndrome; of these, the first two made a full motor recovery, one by 6 weeks follow-up and the second on the same-day post-op evaluation. Overall, five out of seven cases had full resolution of their ankle dorsiflexion pareses. One patient with 1/5 power has not improved. Another with 1/5 weakness improved to normal on the one side and to 3/5 on the other. CONCLUSION: When bilateral foot drop occurs acutely, we encourage the consideration of degenerative spinal disease. Relevant discopathy was observed from L2/3 to L5/S1; aberrant innervation may be at play. Cauda equina syndrome is not necessarily associated with acute bilateral foot drop. The prognosis seems to be pretty good with respect to recovery of the foot drop, especially if partial at presentation and if treated within 48 h.

Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials.

Purpose: Dose information from organ sub-regions has been shown to be more predictive of genitourinary toxicity than whole organ dose volume histogram information. This study aimed to identify anatomically-localized regions where 3D dose is associated with genitourinary toxicities in healthy tissues throughout the pelvic anatomy. Methods and Materials: Dose distributions for up to 656 patients of the Trans-Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar CT dataset. Voxel- based multiple comparison permutation dose difference testing, Cox regression modeling and LASSO feature selection were used to identify regions where 3D dose-increase was associated with late grade ≥ 2 genitourinary dysuria, incontinence and frequency, and late grade ≥ 1 haematuria. This was externally validated by registering dose distributions from the RT01 (up to n = 388) and CHHiP (up to n = 247) trials onto the same exemplar and repeating the voxel-based tests on each of these data sets. All three datasets were then combined, and the tests repeated. Results: Voxel-based Cox regression and multiple comparison permutation dose difference testing revealed regions where increased dose was correlated with genitourinary toxicity. Increased dose in the vicinity of the membranous and spongy urethra was associated with dysuria for all datasets. Haematuria was similarly correlated with increased dose at the membranous and spongy urethra, for the RADAR, CHHiP, and combined datasets. Some evidence was found for the association between incontinence and increased dose at the internal and external urethral sphincter for RADAR and the internal sphincter alone for the combined dataset. Incontinence was also strongly correlated with dose from posterior oblique beams. Patients with fields extending inferiorly and posteriorly to the CTV, adjacent to the membranous and spongy urethra, were found to experience increased frequency. Conclusions: Anatomically-localized dose-toxicity relationships were determined for late genitourinary symptoms in the urethra and urinary sphincters. Low-intermediate doses to the extraprostatic urethra were associated with risk of late dysuria and haematuria, while dose to the urinary sphincters was associated with incontinence.

Reduced Dose Posterior to Prostate Correlates With Increased PSA Progression in Voxel-Based Analysis of 3 Randomized Phase 3 Trials.

PURPOSE: Reducing margins during treatment planning to decrease dose to healthy organs surrounding the prostate can risk inadequate treatment of subclinical disease. This study aimed to investigate whether lack of dose to subclinical disease is associated with increased disease progression by using high-quality prostate radiation therapy clinical trial data to identify anatomically localized regions where dose variation is associated with prostate-specific antigen progression (PSAP). METHODS AND MATERIALS: Planned dose distributions for 683 patients of the Trans-Tasman Radiation Oncology Group 03.04 Randomized Androgen Deprivation and Radiotherapy (RADAR) trial were deformably registered onto a single exemplar computed tomography data set. These were divided into high-risk and intermediate-risk subgroups for analysis. Three independent voxel-based statistical tests, using permutation testing, Cox regression modeling, and least absolute shrinkage selection operator feature selection, were applied to identify regions where dose variation was associated with PSAP. Results from the intermediate-risk RADAR subgroup were externally validated by registering dose distributions from the RT01 (n = 388) and Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer Trial (CHHiP) (n = 253) trials onto the same exemplar and repeating the tests on each of these data sets. RESULTS: Voxel-based Cox regression revealed regions where reduced dose was correlated with increased prostate-specific androgen progression. Reduced dose in regions associated with coverage at the posterior prostate, in the immediate periphery of the posterior prostate, and in regions corresponding to the posterior oblique beams or posterior lateral beam boundary, was associated with increased PSAP for RADAR and RT01 patients, but not for CHHiP patients. Reduced dose to the seminal vesicle region was also associated with increased PSAP for RADAR intermediate-risk patients. CONCLUSIONS: Ensuring adequate dose coverage at the posterior prostate and immediately surrounding posterior region (including the seminal vesicles), where aggressive cancer spread may be occurring, may improve tumor control. It is recommended that particular care be taken when defining margins at the prostate posterior, acknowledging the trade-off between quality of life due to rectal dose and the preferences of clinicians and patients.

Relationships between rectal and perirectal doses and rectal bleeding or tenesmus in pooled voxel-based analysis of 3 randomised phase III trials.

BACKGROUND AND PURPOSE: This study aimed to identify anatomically-localised regions where planned radiotherapy dose is associated with gastrointestinal toxicities in healthy tissues throughout the pelvic anatomy. MATERIALS AND METHODS: Planned dose distributions for up to 657 patients of the Trans Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar computed tomography dataset. Voxel-based multiple comparison permutation dose difference testing, Cox regression modelling and LASSO feature selection were used to identify regions where dose-increase was associated with grade ≥2 rectal bleeding (RB) or tenesmus, according to the LENT/SOMA scale. This was externally validated by registering dose distributions from the RT01 (n = 388) and CHHiP (n = 241) trials onto the same exemplar and repeating the tests on each of these data sets, and on all three datasets combined. RESULTS: Voxel-based Cox regression and permutation dose difference testing revealed regions where increased dose was correlated with gastrointestinal toxicity. Grade ≥2 RB was associated with posteriorly extended lateral beams that manifested high doses (>55 Gy) in a small rectal volume adjacent to the clinical target volume. A correlation was found between grade ≥2 tenesmus and increased low-intermediate dose (∼25 Gy) at the posterior beam region, including the posterior rectum and perirectal fat space (PRFS). CONCLUSIONS: The serial response of the rectum with respect to RB has been demonstrated in patients with posteriorly extended lateral beams. Similarly, the parallel response of the PRFS with respect to tenesmus has been demonstrated in patients treated with the posterior beam.

Trypanosoma brucei colonizes the tsetse gut via an immature peritrophic matrix in the proventriculus.

The peritrophic matrix of blood-feeding insects is a chitinous structure that forms a protective barrier against oral pathogens and abrasive particles1. Tsetse flies transmit Trypanosoma brucei, which is the parasite that causes human sleeping sickness and is also partially responsible for animal trypanosomiasis in Sub-Saharan Africa. For this parasite to establish an infection in flies, it must first colonize the area between the peritrophic matrix and gut epithelium called the ectoperitrophic space. Although unproven, it is generally accepted that trypanosomes reach the ectoperitrophic space by penetrating the peritrophic matrix in the anterior midgut2-4. Here, we revisited this event using fluorescence- and electron-microscopy methodologies. We show that trypanosomes penetrate the ectoperitrophic space in which the newly made peritrophic matrix is synthesized by the proventriculus. Our model describes how these proventriculus-colonizing parasites can either migrate to the ectoperitrophic space or become trapped within peritrophic matrix layers to form cyst-like bodies that are passively pushed along the gut as the matrix gets remodelled. Furthermore, early proventricular colonization seems to be promoted by factors in trypanosome-infected blood that cause higher salivary gland infections and potentially increase parasite transmission.

Gut microbiota composition in Himalayan and Andean populations and its relationship with diet, lifestyle and adaptation to the high-altitude environment.

Human populations living at high altitude evolved a number of biological adjustments to cope with a challenging environment characterised especially by reduced oxygen availability and limited nutritional resources. This condition may also affect their gut microbiota composition. Here, we explored the impact of exposure to such selective pressures on human gut microbiota by considering different ethnic groups living at variable degrees of altitude: the high-altitude Sherpa and low-altitude Tamang populations from Nepal, the high-altitude Aymara population from Bolivia, as well as a low-altitude cohort of European ancestry, used as control. We thus observed microbial profiles common to the Sherpa and Aymara, but absent in the low-altitude cohorts, which may contribute to the achievement of adaptation to high-altitude lifestyle and nutritional conditions. The collected evidences suggest that microbial signatures associated to these rural populations may enhance metabolic functions able to supply essential compounds useful for the host to cope with high altitude-related physiological changes and energy demand. Therefore, these results add another valuable piece of the puzzle to the understanding of the beneficial effects of symbiosis between microbes and their human host even from an evolutionary perspective.

Genetic manipulation allows in vivo tracking of the life cycle of the son-killer symbiont, Arsenophonus nasoniae, and reveals patterns of host invasion, tropism and pathology.

Maternally heritable symbionts are common in arthropods and represent important partners and antagonists. A major impediment to understanding the mechanistic basis of these symbioses has been lack of genetic manipulation tools, for instance, those enabling transgenic GFP expression systems for in vivo visualization. Here, we transform the 'son-killer' reproductive parasite Arsenophonus nasoniae that infects the parasitic wasp Nasonia vitripennis with the plasmid pOM1-gfp, re-introduce this strain to N. vitripennis and then used this system to track symbiont life history in vivo. These data revealed transfer of the symbiont into the fly pupa by N. vitripennis during oviposition and N. vitripennis larvae developing infection over time through feeding. A strong tropism of A. nasoniae to the N. vitripennis ovipositor developed during wasp pupation, which aids onward transmission. The symbiont was also visualized in diapause larvae. Occasional necrotic diapause larvae were observed which displayed intense systemic infection alongside widespread melanotic nodules indicative of an active but failed immune response. Our results provide the foundation for the study of this symbiosis through in vivo tracking of the fate of symbionts through host development, which is rarely achieved in heritable microbe/insect interactions.

Similarity clustering-based atlas selection for pelvic CT image segmentation.

PURPOSE: To demonstrate selection of a small representative subset of images from a pool of images comprising a potential atlas (PA) pelvic CT set to be used for autosegmentation of a separate target image set. The aim is to balance the need for the atlas set to represent anatomical diversity with the need to minimize resources required to create a high quality atlas set (such as multiobserver delineation), while retaining access to additional information available for the PA image set. METHODS: Preprocessing was performed for image standardization, followed by image registration. Clustering was used to select the subset that provided the best coverage of a target dataset as measured by postregistration image intensity similarities. Tests for clustering robustness were performed including repeated clustering runs using different starting seeds and clustering repeatedly using 90% of the target dataset chosen randomly. Comparisons of coverage of a target set (comprising 711 pelvic CT images) were made for atlas sets of five images (chosen from a PA set of 39 pelvic CT and MR images) (a) at random (averaged over 50 random atlas selections), (b) based solely on image similarities within the PA set (representing prospective atlas development), (c) based on similarities within the PA set and between the PA and target dataset (representing retrospective atlas development). Comparisons were also made to coverage provided by the entire PA set of 39 images. RESULTS: Exemplar selection was highly robust with exemplar selection results being unaffected by choice of starting seed with very occasional change to one of the exemplar choices when the target set was reduced. Coverage of the target set, as measured by best normalized cross-correlation similarity of target images to any exemplar image, provided by five well-selected atlas images (mean = 0.6497) was more similar to coverage provided by the entire PA set (mean = 0.6658) than randomly chosen atlas subsets (mean = 0.5977). This was true both of the mean values and the shape of the distributions. Retrospective selection of atlases (mean = 0.6497) provided a very small improvement over prospective atlas selection (mean = 0.6431). All differences were significant (P < 1.0E-10). CONCLUSIONS: Selection of a small representative image set from one dataset can be utilized to develop an atlas set for either retrospective or prospective autosegmentation of a different target dataset. The coverage provided by such a judiciously selected subset has the potential to facilitate propagation of numerous retrospectively defined structures, utilizing additional information available with multimodal imaging in the atlas set, without the need to create large atlas image sets.