Physician and investigator John Wood, MD, Ph.D. of Childrens Hospital of Los Angeles specializes in studying the challenges facing SCD patients. He has currently focused his attention on how oxygen delivery and blood flow are affected by SCD. Results of Dr. Wood’s study were reported in Medical News and published in the American Journal of Hematology by lead author Yaqiong Chai, a senior Ph.D. candidate.
Dr. Wood’s team discovered a disparity in certain areas of the brain with the use of arterial spin labeling that measures blood flow. His study is the first to use the spin labeling method to quantify oxygen delivery to grey and white matter separately in the brain.
Although oxygen delivery to the brain remained unchanged, it was reduced by 35% in delivery to the white matter in the brain, which is where the majority of silent strokes occur in SCD patients.
Dr. Wood explained that they have been successful in preventing large vessel strokes. He was referring to occurrences where brain cells die within minutes of being deprived of oxygen. This results in blindness or paralysis. However, despite this success, patients with SCD still suffer from silent strokes.
About Sickle Cell Disease (SCD)
Sickle Cell Disease is a rare, inherited and devastating disease causing a genetic mutation that affects the protein molecule hemoglobin. This important molecule is found in red blood cells that carry oxygen from the lungs to tissues in the body then returns carbon dioxide back to the lungs.
In SCD, a reduced amount of oxygen is transported to these vital organs and tissues. Blood cells are then transformed into a crescent shape and settle into the smallest blood vessels blocking blood flow. These events not only cause excruciating pain, but the SCD patients are also at extreme risk of a stroke, which is the leading cause of death.
Symptoms of SCD
The earliest symptoms of SCD are symptoms of anemia that include fatigue, jaundice, and swelling of the hands and feet. As the disease progresses, complications arise such as infections, episodes of severe pain called pain crises, and delayed growth.
Children generally do not experience pain during the intervals between pain crises. However, adults and adolescents may suffer ongoing pain. SCD may affect a patient’s spleen, eyes, brain, liver, lungs, kidneys, heart, penis, bones, joints or skin. Symptoms and severity of the disease vary widely among patients.
Treatment for SCD
Currently, the only cure for SCD is a bone marrow transplant. Only a small number of SCD patients are eligible for the transplant.
However, effective treatments are available that can reduce symptoms and prolong life. As in many diseases, early diagnosis and preventing complications through regular medical care is critical. Continuous medical attention not only contributes to a patient’s well being but may establish an improved quality of life.
About Silent Strokes
Dr. Wood is attempting to find the cause of silent strokes that prevent patients from performing routine tasks at home, work or school.
It would appear that since the blood cells are damaged by SCD and oxygen to the brain is reduced, the simple answer is that this chain of events will cause a stroke.
But upon further examination, Dr. Wood found this is not the case. That oxygen is not reduced when transported to the brain of SCD patients. He found that the body compensates for the reduced oxygen content of the blood by increasing blood flow to the brain.
If oxygen to the brain was not reduced, then why were people experiencing silent strokes?
Dr. Wood thought that there may be a distribution problem. Where was the blood actually flowing?
That is how and why, by using arterial spin labeling, Dr. Wood and team discovered that the white matter of the brain was reduced by more than one-third in SCD patients resulting in silent strokes.
About Grey Matter and White Matter
Neurons are brain cells that store information and are found in grey matter. On the other hand white matter differs from grey matter as it is the network of highways in the brain used by neurons to send out this information.
It became clear to Dr. Wood that since it is critical to keep neurons alive for survival, the body prioritizes neurons in favor of grey matter. It is well established that the body adjusts blood flow to meet challenges like decreased oxygen.
For instance, the body prioritizes blood flow and sends it in increased amounts to our muscles during exercise but decreases it during that same period to our digestive tract. Similarly, this scenario plays out when oxygen is low and blood flow is diverted to neurons in the grey matter to prevent their death. At the same time, when anemia is severe, less oxygen is delivered to the white matter.
The study conducted by Dr. Wood provides a better understanding of strokes in SCD. His findings also shed light on anemia in general which is a growing concern of the elderly.
Dr. Wood also hopes that it will help the medical community to assess how current and future SCD treatments such as novel gene therapy affect the brain.