Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04777630 |
| Other study ID # |
PID15262 |
| Secondary ID |
IRAS No: 290078 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2021 |
| Est. completion date |
December 20, 2023 |
Study information
| Verified date |
May 2024 |
| Source |
University of Oxford |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Charles Bonnet Syndrome (CBS) is a condition in which people experience complex visual
hallucinations, such as 'Acrobats balancing on bicycles' or 'Spiders crossing meals'. The
condition usually occurs in people who have significant vision loss due to eye disease. The
aim of this project is to help understand how these hallucinations come about.
In the healthy visual system, the eye provides input to a large area of the brain that
performs the computations required to allow us to see the world. There are specialised brain
regions responsible for processing of faces, objects, motion and colour. When the eye is no
longer working, these parts of the brain lose their input and this may lead to abnormal
activity.
Not all people with eye disease and vision loss develop CBS, so the investigators will use
magnetic resonance imaging (MRI) to compare the brains of people with and without the
condition. In particular the investigators are interested in measuring the levels of
chemicals in the visual areas of the brain to see whether they are disrupted in CBS, leading
to the hallucinations. It is possible to measure how the different areas of the visual brain
are connected together and see whether this is altered in CBS, perhaps with increases in the
strength of connection between specialised areas. These measures will be related to
questionnaires about hallucinations and vision. This will be done by comparing low vision who
experience Charles Bonnet visual hallucinations compared to low vision patients who do not
have hallucinations. Assessments will take place at the Wellcome Centre for Integrative
Imaging (WIN) based at the John Radcliffe Hospital.
The study will provide insight into the role of the brain in generating CBS hallucinations,
helping us to design a larger study and eventually to test whether there are interventions to
help improve the condition.
Description:
Charles Bonnet Syndrome (CBS) has been reported in people with visual impairment, and is
surprisingly common with an estimated prevalence of 10-34% of low vision patients from local
audits. It consists of complex visual hallucinations such as seeing snakes rising from
people's heads or elephants inside a room (see review, Carpenter, Jolly et al. 2019).
Patients experience CBS hallucinations over many years, and although they retain knowledge it
is not real, the hallucinations can be frightening and cause considerable distress. Patients
with CBS have a lower quality of life compared to patients with vision loss without CBS.
Moreover, CBS is under reported due to the fear of being labelled with mental health disease,
adding to the negative consequences.
There is currently no established treatment for CBS, with the mainstay of management in low
vision clinics revolving around reassurance. Many patients receive inappropriate care from
other healthcare practitioners as reported by Judith Potts, founder of Esme's Umbrella, a
patient support charity dedicated to Charles Bonnet Syndrome. A clearer understanding of the
mechanisms underlying CBS would help to ensure the medical community takes the condition
seriously and therefore adequately counsel presenting patients. In addition, understanding
the neural mechanisms of CBS can provide a model for investigating how the brain reorganizes
in response to sensory impairment and may eventually lead to improvement in the management
and treatment of the neurological consequences of eye disease.
Visual processing becomes more complex throughout the pathway from the retina, primary visual
cortex to the more specialised processing in higher visual areas. Thus, the complex nature of
the hallucinations in CBS (faces, objects, animals), in spite of blurred vision, appears to
implicate the higher visual areas in the visual ventral stream that are known to be process
objects.
Neurotransmitters are the chemicals that allow communication across the brain. Some
neurotransmitters increase the activity in the brain (excitatory) and others reduce activity
(inhibitory). A candidate mechanism for CBS from computational modelling is the imbalance of
excitation:inhibition: loss of feedforward visual input may give greater prominence to
feedback in higher visual areas, causing hallucinations. A recent EEG study has provided
experimental support, showing that hyperexcitability of the visual cortex was a key
difference between people who have hallucinations versus those who do not. A critical proof
of this theory would require measurement of excitatory and inhibitory neurochemicals,
glutamate and GABA respectively, in visual areas. This is still outstanding and will be
tackled by this study. MRS-imaging is a cutting-edge method to quantify the concentration of
neurochemicals in the brain. Rather than providing a single measurement from a large volume
of tissue (30x30x30mm), this technique provides high spatial resolution (5x5x20mm)
measurements that permits comparison across the visual cortex. MRSI is the only technique
that can non-invasively quantify neurochemicals in the living human brain, and MRS-imaging
can provide concentrations of the neurotransmitters in multiple locations, which can then be
compared across groups.
In summary, based on previous work and the nature of the hallucinations, the investigators
predict that patients with CBS likely show 1) changes in the neurotransmitter balance across
the visual cortex; 2) increased influence of feedback mechanisms from higher visual areas and
3) abnormal activity in the ventral visual stream to visual stimulation. Our goal is to
characterise the visual cortex of CBS patients by using rigorous non-invasive multi-modal MR
imaging techniques. Using state-of-the-art methods, the team will measure concentrations of
excitatory and inhibitory neurotransmitters, identify changes in connectivity, and measure
evoked visual activity in patients with CBS and visually impaired participants without CBS.
In addition, the team will obtain clinical evaluation and qualitative assessments of
hallucinations.
