Joint Brain Research UK - Royal College of Surgeons of England Research Fellowship
Neurosurgical trainee Ahmad Ali was awarded this joint research fellowship in 2023, to take forward research that aims to improve quality of life for patients with low-grade gliomas.
Surgical intervention is key to the treatment of these brain tumours, increasing survival and delaying progression to high-grade glioma, but the surgery itself can cause side-effects, including cognitive impairment.
Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation that has been used successfully to treat depression and chronic pain, as well as to reduce cognitive impairments associated with other conditions.
During this Fellowship, Ahmad successfully laid the groundwork for a pilot study trialling the use of TMS to reduce cognitive impairment following surgery for low-grade glioma. As a result, Ahmad is now being funded through a three-year NIHR Doctoral Fellowship to deliver a proof-of-concept study evaluating the cognitive effects of TMS.
Whilst neurosurgery is central to the treatment of brain tumours, alleviating life-threatening symptoms and extending lives, the surgery can cause other problems – including problems with memory, attention and other cognitive functions. Ahmad was keen to find ways to reduce the risk of these cognitive issues and to improve quality of life for his patients. He focussed specifically on patients with low-grade gliomas (LGG), a group that he feels is hit particularly hard by cognitive impairment.
Ahmad’s research used a technique called Transcranial Magnetic Stimulation (TMS), in which magnetic fields are applied non-invasively to stimulate a part of the brain. If done repetitively to the same part of the brain, TMS can induce long-lasting changes to the wiring of the targeted area. The benefits have been demonstrated in patients with a range of conditions; TMS is now used routinely to help patients with depression and chronic pain, and trials have demonstrated improved cognition in patients with Alzheimer’s disease, and improvements in upper limb function in glioma patients.
There are many parameters that affect whether TMS works – including, for example, the targeted area of the brain and the method for identifying the target, stimulation frequency and intensity, coil positioning, and the timing and number of sessions. It is paramount, therefore, that these parameters are carefully controlled in any trials of the technique.
During this project Ahmad achieved three key aims: (1) he established a database of patients with LGG that can be used to identify patients who are eligible for a proof-of-concept trial and he met with these patients to design the details of this trial; (2) he undertook a comprehensive meta-analysis of protocols used in previous TMS studies that can be used to guide the selection of the optimal TMS parameters in the proof-of-concept trial; and (3) he established a pipeline for analysing the Magnetic Resonance Imaging (MRI) scans of patients with brain tumours to create personalised stimulation targets for TMS.
This work has created the evidence base for a non-invasive form of brain stimulation that could improve cognitive abilities for patients and, more specifically, has enabled the careful planning of a proof-of-concept study that will begin to establish the potential benefits of TMS for patients with LLG.
Brain stimulation offers significant potential for creating positive changes in the brain. However, most stimulation methods are surgical, which requires significant risk for patients. Non-surgical forms of brain stimulation are less risky, and the potential of TMS as a tool to aid repair of the brain is widely recognised. However, there are many parameters that affect whether it works and it is paramount, therefore, that any use of TMS is done properly and consistently.
Ahmad’s work has informed the design of a proof-of-concept study as the next step towards a clinical trial to establish whether TMS can reduce post-operative cognitive deficits in LGG patients. These cognitive deficits can be enormously debilitating for patients, reducing independence and contributing to a loss of sense of self. Establishing a non-invasive way to restore cognitive function in these patients would have an enormous impact on quality of life, with applicability not only to LGG and other types of brain tumour but a range of other conditions such as epilepsy and traumatic brain injury.
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