Researchers at the Federal University of São Paulo were able | Figure 1

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Researchers at the Federal University of São Paulo were able to reduce lesions caused by cerebral ischemia in mice using stem cells. The technique can aid in the recovery of victims of ischemic stroke, which can cause serious sequelae, such as loss of movement, and even lead to death.

It is not the first time scientists have tried to use stem cells to recover a damaged area of the brain from mice. In previous trials, however, when implanted directly into the lesion, almost no cell survived (0.005%). Those who survived migrated to other regions of the brain. When injected into the bloodstream, they were retained in the kidneys or lungs.

What made the difference this time was the use of a material that, in addition to being biocompatible, increases the survival of the stem cells and causes them to remain in the area of the lesion, reducing inflammation. After a few months, with the area largely recovered, the material is fully absorbed by the body.

Researchers now want to test the stem cell technique for traumatic brain injury, where there is loss of part of the brain. "Today, when the brain mass is lost, the hemorrhage is controlled and the surgery is performed, but what has been lost is lost. There is no way to improve. This could be a new treatment," explains researcher Laura Zamproni.

Source: Unifesp.

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Review question
How effective and safe is cell‐based therapy in people with ALS/MND, when we compare it with an inactive treatment or no treatment?

Background
Amyotrophic lateral sclerosis (ALS; also known as motor neuron disease or MND) is a condition in which nerves in the brain and spinal cord that control movement (motor neurons) stop working. A person with ALS/MND has difficulty moving, swallowing, chewing and speaking, which become worse over time. Half of people with ALS/MND die within three years of their first symptoms. Weakness of muscles used in breathing often leads to death. The condition currently has no cure. Current treatment approaches largely focus on relieving symptoms to improve the quality of life of those affected.

Cell‐based therapy can be defined as injection of cellular material into a person to treat disease. Various types of cell‐based therapies have been tried in ALS/MND, including stem cell therapy. Stem cell therapy aims to provide new motor neurons, which may help stop or slow down disease progression in people with ALS/MND. Previous reviews supported the use of cell‐based therapy as a potential means of delaying the disease course in ALS/MND, but these were mainly based on preclinical animal models. Randomised controlled trials (RCTs) provide the most reliable evidence. In RCTs, one group receives the test treatment, and the other, 'control' group has an alternative treatment, a dummy treatment (placebo) or no treatment. Well‐performed RCTs provide the best evidence. Studies with no untreated group for comparison and small clinical trials have found no clinical benefits. Limited data from non‐RCTs involving a small number of people with ALS/MND and a short follow‐up period suggested that cell‐based therapy may slow disease progression. There is currently no approved cell‐based therapy for ALS/MND. We undertook this review to assess the RCT evidence now becoming available.

Study characteristics
Cochrane review authors searched medical databases for clinical trials. They found two completed RCTs that assessed the effects of cell‐based therapy over a six‐month follow‐up period. One study was not fully published and did not provide numerical data. Both studies were funded by stem cell companies. One study, which included 64 people with ALS/MND, provided data. The people taking part in the trial had an average time since symptom onset of about two years. They had mild to moderate problems with motor function (ability to perform physical tasks) at the start of the trial (with an average of 35 on the ALS Functional Rating Scale‐revised, on which a score of 0 indicates greatest impairment and 48 is normal function).

Key results and quality of the evidence
The study provided low‐quality evidence that stem cells obtained from people's own bone marrow (the cells in the centre of bone) did not result in significant side effects. The cell implantation procedure was well tolerated. Based on evidence from this trial, stem cell treatment may slightly reduce decline in motor function at six months, but may not improve breathing or quality of life at four months, or overall survival at six months. Based on the very limited evidence available, any benefit is uncertain due to there being only one poorly conducted study and results within the study varies. We urgently need large, well‐designed clinical trials to establish whether or not cell‐based therapies have a clear clinical benefit in ALS/MND. Major goals of future research are to identify the right type and amount of cells to use, and how best to administer them.

The evidence is up to date as of July 2019.

Review question
We wanted to know whether people treated with anticoagulants (blood‐thinning drugs) soon after having a stroke got better or not, and whether they had problems with bleeding.

Background
Millions of people around the world have a stroke every year. Most strokes take place when a blood clot blocks a blood vessel leading to the brain. When the blood supply to the brain is restricted or blocked, brain cells begin to die. This can lead to brain injury, which can be permanent, causing disability and possibly death. Damage from a stroke can cause arm or leg weakness, or difficulties with language or vision. Strokes are sometimes fatal but more often leave survivors unable to do the things they used to do. Because strokes are common and cause such damage, researchers are looking at ways to get rid of the blood clot soon after the stroke happens. One way to do this is to use blood‐thinning drugs called anticoagulants. If patients respond well to anticoagulants, they might be able to avoid the bad effects of a stroke. The main problem with anticoagulants is that if they cause bleeding, the patient can have very serious outcomes from this.

Search date
The evidence is current to August 2021.

Study characteristics
To find the best answer, we looked for studies in which investigators compared any anticoagulant to another medicine, to a dummy medicine that does not contain any active ingredients (placebo), or to normal care. We included in this updated review 28 studies involving 24,025 people with stroke. Two studies enrolled participants within 12 hours of stroke onset, four within 24 hours, and 10 within 48 hours.

Key results
People treated with anticoagulants did not have less long‐term disability, and they experienced more bleeding. Anticoagulant‐treated patients had a lesser chance of developing blood clots in their legs and in their lungs following their stroke, but these benefits were offset by an increased number of bleeds.

Conclusion
This review did not provide any evidence to suggest that early use of anticoagulants is beneficial overall for people with stroke caused by blood clots. More research is needed to find out if there are ways to select people with stroke who will benefit most from anticoagulants without suffering the bleeding complications.