This study aims to explore the effect of surgically induced visual and neuro-cognitive
defects on patient functioning and quality of life. The aims of this study are:
1. Understand the impact of surgically induced lesions of visual and limbic pathways on
quality of life;
2. Determine anatomical regions and brain networks that lead to deterioration in
quality of life;
3. Determine extent of early recovery from surgically-induced lesions.
Patient Assessment: Patients will be assessed using the following tools.
1. Ophthalmological assessment
Acuity (LogMAR
- - Logarithm of the Minimum Angle of Resolution);
2.
Colour vision (Ishihara);
3. Basic eye exam to exclude pre-existing ocular pathology (e.g. papilloedema
causing a constricted field/enlarged blind spot);
4. Monocular (Humphrey) and binocular (Esterman) visual field tests.
2. MR imaging
- - imaging protocol will include:
1.
Standard, anatomical magnetic resonance imaging (MRI)
2. Diffusion tensor MRI (DTI)
- - to allow tractography of white matter pathways and
to identify post-operative disruption;
3.
Resting state fMRI (rs-fMRI)
- - to explore plasticity and effect of surgery on
functional networks;
4.
3d contrast enhanced T1-weighted sequence (for surgical planning).
3. Assessment of visual functioning
- - using the National Eye Institute Visual Function
Questionnaire-25 (NEI VFQ-25) - this 25 item questionnaire assesses difficulty with
activities that require vision and their impact on quality of life.
4. Health related quality of life
- - will be assessed using the European Organization
for Research and Treatment of Cancer Quality of Life Questionnaire -30 (EORTC-QLQ30)
with the Brain Tumour 20 module (BN20).
5. Cognitive function
- - neuropsychological will be performed using the OCS-Bridge
cognitive screening battery (https://ocs-bridge.
com/about.html) on a tablet
computer. It takes up to 30minutes to complete:
1. The Oxford Cognitive Screen (OCS): assesses language, semantics, orientation,
reading, movement, number knowledge, mental flexibility, spatial attention and
memory.
2. Cambridge Attention, Memory and Perception Tests: covers visual acuity, verbal
and spatial memory, prospective memory, recognition memory, recognition of
emotion and sustained attention.
3. Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder
Assessment (GAD-7): measure anxiety and disturbances of mood.
4. Cognitive reserve
- - will be estimated pre-operatively (only) using the
Cognitive Reserve Questionnaire (CRq) questionnaire that estimates high, medium
and low cognitive reserve.
Timings of assessments will be:
1. Baseline assessment: performed pre-operatively.
2. Early assessment: performed in the immediate post-operative period prior to
discharge (within 72 hours of surgery). Imaging performed at this time point will be
used to determine anatomical disruption following surgery as described in previous
studies.
3. Delayed assessment: before radiotherapy starts (within 6 weeks after surgery) to
assess recovery. Time points later than this will be confounded by radiotherapy.
Analysis of Clinical Data:
Visual deterioration will be defined as either deterioration in visual acuity (reduction
in LogMAR >0.2), or an increase in visual field loss. Deterioration in the NEI-VFQ25 will
be determined by published minimal important clinical differences.
Cognitive deterioration: significant abnormalities in cognition are defined as >2
standard deviations from established data from normal patients.
Changes in quality of life: as the investigators expect undergoing surgery alone may be
associated with deterioration in quality of life, using published, minimally important
clinical differences may not be valid. Instead the investigators will use the reliable
change index (RCI)
- - this this is an individual's score computed as the difference in the
baseline and delayed assessment tests divided by the standard error of the difference of
the test calculated from a cohort of patients who have undergone an image-guided biopsy
(i.e. underwent surgery under anaesthesia with minimal brain disruption) as control
subjects.
MR Image Analysis:
1. Voxel-based lesion-symptom mapping will be used to identify the relationships
between the surgical site location assessed on MRI and DTI with deterioration in
quality of life using methods described in other studies mapping lesions to language
and visual deficits.
2. DTI imaging data will study white matter disruption and will be processed in a
number of ways
Measure metrics of the white matter regions to assess effect of tumour invasion
using our previously developed methods,
2. Tractography of the visual pathways will show injury of these pathways using
previously developed repeatable and reproducible methods developed.
3. Resting state functional MRI will assess changes to the integrity of brain
functional networks and connections. Analysis will include
independent component analysis (ICA) to identify resting-state networks;
2. connectome analysis using graph theory measures that correlate to network
efficiency, and. 3. fractal analysis looks at the complexity of blood oxygen level (BOLD) time
series as a proxy for the capacity for neuronal processing as a global measure
of network disruption.
Objectives and key deliverables: The primary objective will be to assess impact of
developing a new, permanent surgically-induced visual or cognitive lesion has on quality
of life. This will be achieved by understanding the effect of surgically induced
visual/cognitive defects on quality of life. This will be achieved by comparing quality
of life and NEI-VFQ25 scores for patients with and without newly developed surgically
induced deficits.
Secondary objectives will include:
1. Explore which anatomical/functional regions will lead to deterioration in quality of
life, neurocognitive function and NIE-VFQ25 scores. This will be achieved by:
1. Voxel-based lesion-symptom mapping;
2. White matter tracts disrupted (from DTI data).
2. Investigate recovery of surgically-induced visual/cognitive deficits. This will be
studied by comparing visual and cognitive function between initial post-operative
assessment and before starting radiotherapy.
3. Quantifying white matter tract disruption by correlating DTI metrics with
development of new visual deficits.
4. Assess impact of cognitive reserve on surgically induced cognitive deficits by
assessing cognitive decline with different degrees of cognitive reserve.
The investigators will use the data to explore the impact on surgery and changes in
cognition and quality of life with disruption of functional brain networks as an
exploratory outcome.
Patient Numbers: By recruiting 21 patients with visual deficits and comparing their mean
RCI values with 21 patients without such deficits (as controls), an effect size of 0.8
(large) can be detected with 80% probability in a one-sided test (5% type I error rate).
An effect size of 0.6 would be detected with a 60% probability under the same conditions
with that sample size. From our pilot study data the investigators assume a 25% rate of
visual deficit, and therefore 84 patients need to be recruited as a minimum to achieve
the required sample size per group. A further 21 patients with frontal lobe lesions will
be recruited to look for cognitive decline, and then (generously) assume a 15% drop out
figure, so that the total patient numbers will be 120 for this work-package.
