Lay summaries of recently published research results
Using magnetic stimulation to restore swallowing after stroke
A stroke occurs when blood supply to an area of the brain is reduced, often caused by a blockage in one of the blood vessels supplying that area of the brain. This can damage the affected area and means that it may not function properly. This results in some of the common symptoms of stroke such as weakness, speech and swallowing problems.
Transcranial magnetic stimulation is the application of magnetic pulses from a probe above the scalp to stimulate specific areas of the brain. This is a completely painless technique that is currently approved for use in the NHS for other medical problems, such as depression.
Why is the study important?
Dysphagia, or swallowing difficulties, is a common consequence of stroke due to brain damage in the area that controls swallowing and can have a significant impact on the quality of life and recovery after a stroke. People that have suffered a stroke who then develop dysphagia have a higher rate of complications, such as weight loss, or lung infections from accidently inhaling food, also known as aspiration. This results in a higher risk of hospitalisation and death, and may require feeding tubes to ensure patients receive adequate nutrition. However, these feeding tube carry risks of their own, such as infection.
Current techniques to help manage dysphagia primarily involve physical therapy and are usually effective at improving swallowing. However, they are often hindered by the other complications of stroke, such as tiredness and low mood which may make engaging in physical therapy more difficult.
What did the authors do and how did they do it?
Recent research has shown that the healthy side of the brain that has not been affected by stroke can create new connections in an attempt to restore swallowing. The authors targeted this compensation mechanism of the brain by applying magnetic stimulation to the healthy side of the brain to activate it and encourage it to create these new connections more quickly.
They recruited 38 individuals of varying age, sex, and ethnicity, who had recently suffered a stroke and developed significant dysphagia. They applied magnetic stimulation, alongside swallowing exercises, in two 20 minute sessions a day for 5 consecutive days. Their aim was to measure any improvements in the risk of accidentally inhaling food (aspiration) and measuring food intake. An improvement in either might represent an overall improvement in swallowing. The study was double-blinded , which means that both the researchers and participants were not aware who was receiving magnetic stimulation and who was not. This ensures that the results are not affected by bias and is the gold-standard of clinical trials.
What are the results?
The authors found that people who underwent transcranial magnetic stimulation had similar scores on the risk of aspiration to those that did not. This suggests that the transcranial magnetic stimulation alone did not directly reduce the risk of inhaling food. However, these scoring systems have been criticised as they are subjective measures and research has shown that some clinicians would give different scores to the same patient.
Nevertheless, the aim of any treatment for dysphagia is to improve overall food intake. The authors found that after 1 month, overall food intake was significantly higher in those that received transcranial magnetic stimulation compared to those who did not. This suggests an improvement in overall swallowing. Importantly, no participant withdrew from the study due to discomfort or pain and no participant suffered from a direct complication of the transcranial magnetic stimulation. This suggests that this method is painless, well tolerated, and easy to engage with, particularly since all the patients recruited were within the first few days of their stroke.
What do the finding mean going forward for people with the disease?
Transcranial magnetic stimulation has been deemed to be safe and effective by the NHS for other medical problems. The findings of this study are promising and may mean that this technique, alongside physical therapy, is integrated into stroke rehabilitation programmes to help to restore a safe swallow for people with dysphagia. This can reduce the risk of complications and may significantly improve the quality of life after a stroke.
Author: Hamish Patel
Can an experimental drug protect neurons from injury after stroke?
A stroke occurs when the blood supply to the brain is either reduced or stopped. The most common type of stroke is an ischemic stroke, caused due to a blood clot in the blood vessels that supply blood to the brain.
Like all organs in the body, the brain relies on nutrients (such as glucose, or sugar) and oxygen, delivered via blood, for it to carry out its functions. An adequate supply of glucose and oxygen is essential to maintain the health of neurons, the cells that send and receive signals in the brain. Therefore, when a stroke occurs due to inadequate blood supply, neurons in the brain are deprived of oxygen and glucose. This process, called oxygen and glucose deprivation (OGD) causes neuronal injury and death post-stroke.
All cells, including neurons, contain microscopic substances called molecules. These enable the cell to carry out various functions by interacting with one another. One such molecule, called brain-derived neurotrophic factor (BDNF), plays a key role in the survival of neurons. It exerts its effects by activating another molecule, called TrkB, which in turn activates another molecule, which activates another. Such a series of events is called a molecular cascade or a signalling pathway. The signalling pathway that is activated by BDNF is called the BDNF/TrkB/Akt pathway, or simply the TrkB/Akt pathway.
The TrkB/Akt pathway has been linked to neuronal survival and is thought to protect the neurons against oxygen and glucose deprivation (OGD). Since OGD is thought to be the mechanism of neuronal death after stroke, activating this pathway might provide a method to improve the health of neurons and facilitate their recovery post-stroke.
Research has shown that the TrkB/Akt pathway can be activated artificially by an experimental drug called 7,8-dihydroxyflavone (7,8-DHF), which mimics the effects of BDNF. Some studies have shown the beneficial effects of 7,8-DHF in other neurodegenerative disorders, but its potential benefit has not been explored in the context of ischemic stroke.
Why is this study important?
Ischemic strokes account for about 85% of strokes worldwide. They are a leading cause of long-term disability and death worldwide. Therefore, developing new treatment strategies for ischemic stroke is extremely important. This study provides insight into the mechanisms that are affected at the cellular level during ischemic stroke. These pathways offer potential targets for the development of new therapies that may eventually benefit the patient community.
What did the authors do and how did they do it?
Using animal cells to model diseases in humans is a common practice to test the effects of experimental drugs, whose effects are unknown, as these cannot be tested directly in humans. The use of animals in medical research is a highly regulated process with many ethical, legal, and moral considerations.
In this study, the researchers used neurons derived from rats to investigate whether 7,8-DHF can protect neurons from OGD-induced injury.
The researchers grew the rat neurons in conditions lacking oxygen and glucose, so as to mimic the OGD that accompanies stroke in people. A subset of these cells was treated with 7,8-DHF to determine whether it had potential beneficial effects as compared to the control cells, that were untreated. A range of tests were performed to confirm that OGD caused the death of neurons, and to subsequently determine whether 7,8-DHF treatment could aid neuronal recovery and survival via the activation of the TrkB/Akt pathway.
What are the results?
To achieve the aims set out in this study, the researchers used a range of tests to determine the effects of OGD and 7,8-DHF treatment on neurons. These tests are aimed at detecting markers for cell death, cell survival and activation of the TrkB/Akt pathway. The tests were carried out in a test group of neurons – that were treated with 7,8-DHF after OGD, and a control group of neurons – that were subjected to OGD and left untreated. Comparing the results from the test and control group enabled the researchers to confirm that the effects observed after performing the experiments are indeed due to the treatment of 7,8-DHF and not any other external factor.
The researchers found that OGD induced the death of neurons. They also found that the cells treated with 7,8-DHF showed fewer markers of cell death, thus suggesting that 7,8-DHF treatment protected the neurons from OGD-induced cell death.
The researchers also found that the TrkB/Akt pathway was less active in the untreated neurons, and that this reduced activity was reversed in the neurons treated with 7,8-DHF. This is in line with other studies that have investigated 7,8-DHF as a potential therapy in other neurodegenerative disorders.
Taken together, these results suggest that 7,8-DHF treatment can improve cell survival by activating the TrkB/Akt pathway post-stroke.
What do these findings mean going forward for people with the disease?
These findings provide insights into the links between the BDNF/TrkB/Akt signalling pathway and neuronal survival in the context of stroke. The findings of this study suggest that by influencing the activity of the BDNF/TrkB/Akt pathway, we might alleviate the damage caused to cells by OGD after ischemic stroke. This might allow for the development of new effective treatment options for patients post-stroke.
Author: S Shivani
Has the COVID-19 pandemic impacted stroke care?
Ischemic stroke takes place when blood flow to the brain is reduced due to an obstruction in a blood vessel supplying the brain. According to the World Health Organisation, 15 million people suffer a stroke worldwide each year, 5 million are fatal strokes. This makes stroke the second leading cause of death.
This report aims to explore whether the ongoing COVID-19 pandemic has caused delays in receiving possibly life-saving treatment for acute ischemic strokes. The time from arrival at hospital to removal of a blood clot through either thrombolytic medication or surgical thrombectomy is crucial in improving the outcome for the patient. Treatment through thrombolysis involves injecting a patient with a medication to break down a clot in a blood vessel and restore blood flow to the affected area of the brain. In cases where this does not work or poses a high risk of bleeding, thrombectomy is used. Here, the blood clot is removed surgically from within the vessel, restoring normal blood flow. Due to the COVID-19 pandemic, delays to treatment may be seen through increased time for decontamination, changing of personal protective equipment or reduced staff numbers due to social distancing or quarantine.
The authors of this report compared time taken from arrival at hospital to treatment administration in patients admitted pre COVID-19 (1st March 2019 – 31st July 2019) to those admitted during COVID19 (1st March 2020 – 31st July 2020). 2955 patients were sampled from 14 US stroke centres, 1491 were admitted pre-COVID-19 and 1464 were admitted during COVID-19.
The standard target is that patients will be treated within 60 minutes of arrival. The report found that patients admitted during COVID-19 had a lower chance of receiving thrombolysis within the 60-minute target window. On average, patients were delayed by 4 minutes. This seemingly insignificant delay could be crucial in achieving a positive outcome for the patient, though data was not collected on the impact this delay had to individual patients. Those 4 minutes could decrease the chances that a patient will make a full recovery without severe functional impairment. The delay was seen between imaging of the brain via CT scan and bolus, or injection of the thrombolytic medication to break down and remove the clot. The use of a CT scan allows doctors to identify the location of the clot and improve the chances that the clot can be removed effectively and safely. The delay in starting treatment is likely due to the time taken to change PPE and decontaminate rooms.
However, in those patients who were treated surgically using a thrombectomy, there was a decrease in treatment time, though not statistically significant. The authors proposed that this was due to an improved waiting time between scan and groin puncture to begin the treatment.
By improving the imaging to treatment time within patients treated with thrombolysis, the impact of COVID-19 on other areas of the healthcare system such as stroke centres may be reduced. This could mean that patients suffering an acute stroke during the COVID-19 pandemic would not experience any delays to their treatment which may damage their chances of a positive outcome.
Author: Ashleigh Howe
Reviewer: Milena De Felice
Could alcohol be protective against stroke?
Research has historically produced conflicting results when it comes to alcohol consumption and stroke risk. Some studies suggest that different types of alcohol have different impacts on stroke risk, while others suggest that light alcohol consumption may even be protective. With 14% of people reporting their alcohol consumption increased over the COVID-19 pandemic, it is more important than ever to explore how this may impact their future stroke risk.
This paper aimed to address the conflicting research through exploring the impact of drinking patterns on ischemic stroke, which is caused by reduced oxygen reaching the brain.
Data was collected from a large existing cohort in Korea, using 152,469 middle aged participants. Participants’ drinking pattern was defined using the frequency of alcohol intake and the amount they drank each time. Five drinking patterns were identified: 1) abstainers who did not drink alcohol; 2) those who drank less than 30g a day less than 5 days a week; 3) those who drank less than 30g a day and more than 5 days a week; 4) those who drank over 30g a day and less than 5 days a week; 5) those who drank more than 30g a day and more than 5 days a week. These figures were collected through a questionnaire. Participants were followed up for an average period of 9 years, providing long term data on their future stroke risk through health insurance details.
Drinker group 4, who were drinking more alcohol in each sitting but less frequently showed lower stroke risk than abstainers. However, drinking less alcohol more frequently as in drinker group 3 did not show a reduced risk in the first 7 years. Nevertheless, any differences in stroke risk had balanced out by the 7 year follow up, suggesting that the findings do not support the idea that low alcohol intake can reduce stroke risk. Even low alcohol consumption is associated with damaging hypertension, which increases ischemic stroke risk, suggesting that only the abstainer group had a long term reduced stroke risk. Conversely, research has linked moderate alcohol intake to blood clot dissolving effects similar to those seen in medication used to dissolve clots in emergency care. Therefore, it is possible that alcohol consumption has a variety of effects on stroke risk, and while harmful effects such as hypertension may be more severe in older age, the protective effects may not be able to counteract the increased risk conferred by general health and age.
This paper concluded that while light drinking may reduce stroke risk, it fails to have a long-term protective effect. As regular alcohol intake is associated with a host of long-term negative effects such as liver damage, it would be unwise to promote light drinking as a form of protection against stroke risk. As any protective effects of alcohol seem to be fleeting during midlife, it may be worth further exploring how alcohol could protect against stroke and whether this could be maintained into later life and serve to reduce stroke risk across the lifespan. Overall, research does not currently support that even low alcohol intake can reduce stroke risk.
Author: Ashleigh Howe
Reviewer: Milena De Felice