Oxford brain health clinic: protocol and research database.

INTRODUCTION: Despite major advances in the field of neuroscience over the last three decades, the quality of assessments available to patients with memory problems in later life has barely changed. At the same time, a large proportion of dementia biomarker research is conducted in selected research samples that often poorly reflect the demographics of the population of patients who present to memory clinics. The Oxford Brain Health Clinic (BHC) is a newly developed clinical assessment service with embedded research in which all patients are offered high-quality clinical and research assessments, including MRI, as standard. METHODS AND ANALYSIS: Here we describe the BHC protocol, including aligning our MRI scans with those collected in the UK Biobank. We evaluate rates of research consent for the first 108 patients (data collection ongoing) and the ability of typical psychiatry-led NHS memory-clinic patients to tolerate both clinical and research assessments. ETHICS AND DISSEMINATION: Our ethics and consenting process enables patients to choose the level of research participation that suits them. This generates high rates of consent, enabling us to populate a research database with high-quality data that will be disseminated through a national platform (the Dementias Platform UK data portal).

Adapting UK Biobank imaging for use in a routine memory clinic setting: The Oxford Brain Health Clinic.

The Oxford Brain Health Clinic (BHC) is a joint clinical-research service that provides memory clinic patients and clinicians access to high-quality assessments not routinely available, including brain MRI aligned with the UK Biobank imaging study (UKB). In this work we present how we 1) adapted the UKB MRI acquisition protocol to be suitable for memory clinic patients, 2) modified the imaging analysis pipeline to extract measures that are in line with radiology reports and 3) explored the alignment of measures from BHC patients to the largest brain MRI study in the world (ultimately 100,000 participants). Adaptations of the UKB acquisition protocol for BHC patients include dividing the scan into core and optional sequences (i.e., additional imaging modalities) to improve patients' tolerance for the MRI assessment. We adapted the UKB structural MRI analysis pipeline to take into account the characteristics of a memory clinic population (e.g., high amount of white matter hyperintensities and hippocampal atrophy). We then compared the imaging derived phenotypes (IDPs) extracted from the structural scans to visual ratings from radiology reports, non-imaging factors (age, cognition) and to reference distributions derived from UKB data. Of the first 108 BHC attendees (August 2020-November 2021), 92.5 % completed the clinical scans, 88.0 % consented to use of data for research, and 43.5 % completed the additional research sequences, demonstrating that the protocol is well tolerated. The high rates of consent to research makes this a valuable real-world quality research dataset routinely captured in a clinical service. Modified tissue-type segmentation with lesion masking greatly improved grey matter volume estimation. CSF-masking marginally improved hippocampal segmentation. The IDPs were in line with radiology reports and showed significant associations with age and cognitive performance, in line with the literature. Due to the age difference between memory clinic patients of the BHC (age range 65-101 years, average 78.3 years) and UKB participants (44-82 years, average 64 years), additional scans on elderly healthy controls are needed to improve reference distributions. Current and future work aims to integrate automated quantitative measures in the radiology reports and evaluate their clinical utility.

CLIPPERS: A case report with radiology, three serial biopsies and a literature review.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system inflammatory disorder primarily affecting the brainstem and cerebellum. We report a case of CLIPPERS in a 45-year-old man presenting with left facial numbness and dizziness. Imaging studies were conducted repeatedly over an 8-year follow-up period. Given diagnostic uncertainty in the early stages of the disease, three serial biopsies were obtained, which together with the clinical and radiological findings, led to the diagnosis. This case highlights the diagnostic challenges regarding the rare entity of CLIPPERS and discusses the main differential diagnoses that are necessary to consider. Additionally, some of the atypical features of this case, including the presenting finding of a large, solidly enhancing lesion on radiological imaging and prominent plasma cells on pathology, contribute to expanding the spectrum of appearances for CLIPPERS.

MRS and DTI evidence of progressive posterior cingulate cortex and corpus callosum injury in the hyper-acute phase after Traumatic Brain Injury.

The posterior cingulate cortex (PCC) and corpus callosum (CC) are susceptible to trauma, but injury often evades detection. PCC Metabolic disruption may predict CC white matter tract injury and the secondary cascade responsible for progression. While the time frame for the secondary cascade remains unclear in humans, the first 24 h (hyper-acute phase) are crucial for life-saving interventions. Objectives: To test whether Magnetic Resonance Imaging (MRI) markers are detectable in the hyper-acute phase and progress after traumatic brain injury (TBI) and whether alterations in these parameters reflect injury severity. Methods: Spectroscopic and diffusion-weighted MRI data were collected in 18 patients with TBI (within 24 h and repeated 7-15 days following injury) and 18 healthy controls (scanned once). Results: Within 24 h of TBI N-acetylaspartate was reduced (F = 11.43, p = 0.002) and choline increased (F = 10.67, p = 0.003), the latter driven by moderate-severe injury (F = 5.54, p = 0.03). Alterations in fractional anisotropy (FA) and axial diffusivity (AD) progressed between the two time-points in the splenium of the CC (p = 0.029 and p = 0.013). Gradual reductions in FA correlated with progressive increases in choline (p = 0.029). Conclusions: Metabolic disruption and structural injury can be detected within hours of trauma. Metabolic and diffusion parameters allow identification of severity and provide evidence of injury progression.

Early detection of cerebral microbleeds following traumatic brain injury using MRI in the hyper-acute phase.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability in people under 45. Advanced imaging techniques to identify injury and classify severity in the first few hours and days following trauma could improve patient stratification and aid clinical decision making. Traumatic cerebral microbleeds (TCMBs), detectable on magnetic resonance susceptibility weighted imaging (SWI), can be used as markers of long-term clinical outcome. However, the relationship between TCMBs and injury severity in the first few hours after injury, and their natural evolution, is unknown. METHODS: We obtained SWI scans in 10 healthy controls, and 13 patients scanned 3-24h following TBI and again at 7-15days. TCMBs were identified and total volume quantified for every lesion in each scan. RESULTS: TCMBs were present in 6 patients, all with more severe injury classified by GCS. No lesions were identified in patients with an initial GCS of 15. Improvement in GCS in the first 15days following injury was significantly associated with a reduction in microbleed volume over the same time-period. CONCLUSION: MRI is feasible in severely injured patients in the first 24h after trauma. Detection of TCMBs using SWI provides an objective early marker of injury severity following trauma. TCMBs revealed in this time frame, offer the potential to help determine the degree of injury, improving stratification, in order to identify patients who require admission to hospital, transfer to a specialist center, or an extended period of intubation on intensive care.

Comparing the sensitivity of linear and volumetric MRI measurements to detect changes in the size of vestibular schwannomas in patients with neurofibromatosis type 2 on bevacizumab treatment.

OBJECTIVE: To compare the sensitivity of linear and volumetric measurements on MRI in detecting schwannoma progression in patients with neurofibromatosis type 2 on bevacizumab treatment as well as the extent to which this depends on the size of the tumour. METHODS: We compared retrospectively, changes in linear tumour dimensions at a range of thresholds to volumetric tumour measurements performed using Brainlab iPlan(®) software (Feldkirchen, Germany) and classified for tumour progression according to the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria. RESULTS: Assessment of 61 schwannomas in 46 patients with a median follow-up of 20 months (range 3-43 months) was performed. There was a mean of 7 time points per tumour (range 2-12 time points). Using the volumetric REiNS criteria as the gold standard, a sensitivity of 86% was achieved for linear measurement using a 2-mm threshold to define progression. CONCLUSION: We propose that a change in linear measurement by 2 mm (particularly in tumours with starting diameters 20-30 mm, the majority of this cohort) could be used as a filter to identify cases of possible progression requiring volumetric analysis. This pragmatic approach can be used if stabilization of a previously growing schwannoma is sufficient for a patient to continue treatment in such a circumstance. ADVANCES IN KNOWLEDGE: We demonstrate the real-world limitations of linear vs volumetric measurement in tumour response assessment and identify limited circumstances where linear measurements can be used to determine which patients require the more resource-intensive volumetric measurements.

Bevacizumab in neurofibromatosis type 2 (NF2) related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation.

BACKGROUND: NF2 patients develop multiple nervous system tumors including bilateral vestibular schwannomas (VS). The tumors and their surgical treatment are associated with deafness, neurological disability, and mortality.Medical treatment with bevacizumab has been reported to reduce VS growth and to improve hearing. In addition to evaluating these effects, this study also aimed to determine other important consequences of treatment including patient-reported quality of life and the impact of treatment on surgical VS rates. METHODS: Patients treated with bevacizumab underwent serial prospective MRI, audiology, clinical, CTCAE-4.0 adverse events, and NFTI-QOL quality-of-life assessments. Tumor volumetrics were classified according to the REiNs criteria and annual VS surgical rates reviewed. RESULTS: Sixty-one patients (59% male), median age 25 years (range, 10-57), were reviewed. Median follow-up was 23 months (range, 3-53). Partial volumetric tumor response (all tumors) was seen in 39% and 51% had stabilization of previously growing tumors. Age and pretreatment growth rate were predictors of response. Hearing was maintained or improved in 86% of assessable patients. Mean NFTI-QOL scores improved from 12.0 to 10.7 (P < .05). Hypertension was observed in 30% and proteinuria in 16%. Twelve treatment breaks occurred due to adverse events. The rates of VS surgery decreased after the introduction of bevacizumab. CONCLUSION: Treatment with bevacizumab in this large, UK-wide cohort decreased VS growth rates and improved hearing and quality of life. The potential risk of surgical iatrogenic damage was also reduced due to an associated reduction in VS surgical rates. Ongoing follow-up of this cohort will determine the long-term benefits and risks of bevacizumab treatment.

Lessons in the management of post-operative tension pneumocephalus complicating transcranial resection of advanced cutaneous tumours with free flap reconstruction.

Tension pneumocephalus is a rare, but potentially life-threatening complication of transcranial surgery. Whilst commonly described in the field of neurosurgery, little has been published in the context of craniofacial surgery. We describe two cases of post-operative extradural tension pneumocephalus occurring following free myocutaneous latissimus dorsi flap reconstruction of anterior cranial defects following extirpation of advanced recurrent skin carcinomas. These cases illustrate the variation in clinical presentation of this condition, the importance of prompt recognition, urgent radiological investigation and timely decompression, and potential management strategies for minimising the risk of recurrent symptoms.

Congenital conductive hearing loss and multiple synostosis syndrome with analysis of temporal bone CT scan findings.

We present the case of a mother and four children displaying signs of Multiple Synostosis Syndrome (SYNS1) associated with conductive hearing loss. The intra-familial phenotypic variation is due to variable penetrance, which is typical of this syndrome. The child with the most significant hearing loss showed lucency of the otic capsule on temporal bone CT. There is no evidence of this phenomenon associated with SYNS1 in the literature. CT scanning can diagnose certain ossicular chain abnormalities, removing the need for tympanotomy under general anaesthetic. Syndromic hearing loss is progressive and should be monitored where appropriate.

Substantial observer variability in the differentiation between primary intracerebral hemorrhage and hemorrhagic transformation of infarction on CT brain imaging.

BACKGROUND AND PURPOSE: CT remains the most commonly used imaging technique in acute stroke but is often delayed after minor stroke. Interobserver reliability in distinguishing hemorrhagic transformation of infarction from intracerebral hemorrhage may depend on delays to CT but has not been reported previously despite the clinical importance of this distinction. METHODS: Initial CT scans with intraparenchymal hematoma from the first 1000 patients with stroke in the Oxford Vascular Study were independently categorized as intracerebral hemorrhage or hemorrhagic transformation of infarction by 5 neuroradiologists, both blinded and unblinded to clinical history. Thirty scans were reviewed twice. Agreement was quantified by the kappa statistic. RESULTS: Seventy-eight scans showed intraparenchymal hematoma. Blinded pairwise interrater agreements for a diagnosis of intracerebral hemorrhage ranged from kappa=0.15 to 0.48 with poor overall agreement (kappa=0.35; 95% CI, 0.15 to 0.54) even after unblinding (kappa=0.41; 0.21 to 0.60). Blinded intrarater agreements ranged from kappa=0.21 to 0.92. Lack of consensus after unblinding was greatest in patients scanned >or=24 hours after stroke onset (67% versus 25%, P=0.001) and in minor stroke (National Institutes of Health Stroke Scale or=24 hours after minor stroke and in 48% of all 30-day stroke survivors in whom reliable diagnosis would be expected to influence long-term management. CONCLUSIONS: Reliability of diagnosis of intraparenchymal hematoma on CT brain scan in minor stroke is poor, particularly if scanning is delayed. Immediate brain imaging is justified in patients with minor stroke.

Central or atypical skull base osteomyelitis: diagnosis and treatment.

OBJECTIVE: We report cases of central or atypical skull base osteomyelitis and review issues related to the diagnosis and treatment. METHODS: The four cases presented, which were drawn from the Oxford, United Kingdom, skull base pathology database, had a diagnosis of central skull base osteomyelitis. RESULTS: Four cases are presented in which central skull base osteomyelitis was diagnosed. Contrary to malignant otitis externa, our cases were not preceded by immediate external infections and had normal external ear examinations. They presented with headache and a variety of cranial neuropathies. Imaging demonstrated bone destruction, and subsequent microbiological analysis diagnosed infection and prompted prolonged antibiotic treatment. CONCLUSION: We concluded that in the diabetic or immunocompromised patient, a scenario of headache, cranial neuropathy, and bony destruction on imaging should raise the possibility of skull base osteomyelitis, even in the absence of an obvious infective source. The primary goal should still be to exclude an underlying malignant cause.

Gradenigo's syndrome: successful conservative treatment in adult and paediatric patients.

A triad of retro-ocular pain, discharging ear and abducens nerve palsy, as described by Gradenigo, has been recognized for 150 years. It has traditionally been treated with surgery, but recent advances in imaging, allied with improved antibiotic treatment, allow conservative management of these cases. We present two cases of Gradenigo's syndrome: a 6-year-old child and a 70-year-old man, both without cholesteatoma, who were managed without mastoidectomy. They both had full recovery of abducens nerve function, although this took 6 and 12 weeks, respectively. In order to manage patients with Gradenigo's syndrome safely, accurate diagnostic radiology is essential, and our findings are presented and discussed. With changing medical technology, a review of the diagnostic and treatment options for this rare but serious condition, is timely.