New Horizons for Cerebral Palsy Therapy

The leading cause of physical disability in babies and young children is Cerebral Palsy. It affects an estimated two to three children per 1000 live births, and this rate increases to 40 to 100 children per 1000 live births when looking at those who were born (extremely) premature or with a Very Low Birth Weight. Midwife Without Borders sheds light on three new developments that might help us to better understand, cope with and perhaps even treat Cerebral Palsy.

​​Cerebral Palsy

Cerebral palsy (CP) is an umbrella term, and is generally understood to describe “a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain”. These disturbances may occur during pregnancy, in delivery or in the first years of a child’s life. Cerebral Palsy can vary in terms of severity and may be accompanied by “disturbances of sensation, perception, cognition, communication, and behaviour, by epilepsy, and by secondary musculoskeletal problems”.


Risk Factors

There is a great variety of factors that can increase the risk for Cerebral Palsy. Among the maternal risk factors are exposure to toxic substances (like mercury, certain medications, illegal drugs, alcohol), being pregnant of multiples, thyroid gland problems, Rhesus disease, (viral) infections during pregnancy (CMV, Varicella, Rubella, Herpes, Toxoplasmosis, Syphilis), et cetera. A fetus can also be genetically predisposed to certain defects in nerve cell connections in the brain. Antenatal events like periventricular leukomalacia (white matter brain injury) and intraventricular hemorrhage are also risk factors in acquiring Cerebral Palsy. Furthermore, there can be perinatal risk factors like preterm birth, chorioamnionitis, low birth weight, breech position, and a complicated or prolonged labor and delivery. Obstructed fetal circulation during labour can limit the oxygen flow to important organs, like the brain. Postnatal risk factors include Meningitis, seizures, and traumatic injuries to the developing brain.


​​Presentation

According to NICE, Cerebral Palsy may reveal itself by a number of features in the motor behaviour of a child. Any abnormality in movement, tone and motor development may serve as a signal, for instance sudden, uncontrolled movements, stiffness, and being late in head control, rolling and crawling. Another hint may be difficulties in feeding the child. Besides these factors, there are developmental milestones that are delayed in children with Cerebral Palsy. The most common are that these children often don’t sit by 8 months and don’t walk by 18 months, and prefer to use one hand over the other even before reaching the age of 1 year (all ages corrected for gestational age). All these are of course hints, and in case of doubt whether a child has Cerebral Palsy, further research may be required.


​​Cerebral Palsy in Uganda

A remarkable recent study into Cerebral Palsy - available at The Lancet’s website - focusses on Uganda. The researchers state that population based studies into Cerebral Palsy are rare for Low and Middle Income Countries and that theirs is the first of its kind in sub-Saharan Africa. Prevalence of Cerebral Palsy in Uganda was found to be higher than in High Income Countries. This higher prevalence suggests a higher prevalence of Cerebral Palsy risk factors.


The researchers also found that one fourth of the children in their study - a far higher percentage than in High Income Countries - were reported to not have met the possible cause of their Cerebral Palsy until more than four weeks after birth. Often, they note, caregivers would say that those newborns had developed in a normal way until they suddenly fell ill with fever and seizures, after which their motor function was impaired. One possible explanation is Malaria, which is endemic in Uganda and which, in its cerebral variant, causes epileptic seizures, but other brain infections like bacterial Meningitis are also mentioned. Whatever the exact cause, “the combination of a cerebral infection, high fever, and untreated seizures probably increased the risk of unrepairable brain injuries, leading to Cerebral Palsy (or acquired brain injury)”.


The percentage of preterm-born children among the Cerebral Palsy cases was found to be much lower in Uganda (2%) than in High Income Countries (40%). The difference is probably explained by the fact that preterm newborns often don’t survive due to lack of appropriate care.


Robotic Exoskeleton

​​Meanwhile, the American National Institutes of Health (NIH) announced that a team of its researchers have developed a robotic exoskeleton in an effort to treat ‘crouch gait’. This is condition that prevents a proper bending of the knee and stretching of the leg, and it often hampers children with Cerebral Palsy who try to walk. Existing treatments notwithstanding, according to the NIH about 50% of the adults with crouch gait eventually lose their ability to walk. The developers have high hopes: they didn’t develop the skeleton to replace bodily functions that were lost, but to “train a new walking pattern in these children if deployed over an extended time”.


In a first study, seven children between the ages 5 to 19 were included. They all had Cerebral Palsy and could still walk around 9 meters without a walking aid. All seven eventually could walk independent of a therapist or walking aid. Six of the children showed an improvement in knee extension that was equal to or better than the average improvement after surgery. The researchers also found that the use of the skeleton did not impair muscle activity of the knee extensor. Based on the outcomes, they state that “powered knee exoskeletons should be investigated as an alternative to or in conjunction with conventional treatments” for crouch gait. A demonstration video can be watched here.

Regeneration with Stem Cells?

Cerebral Palsy is a condition, not a disease and so far the treatment has mainly been focussed on dealing with it, with options ranging from surgery to all sorts of therapy to improve mobilisation and development. A recent study published in Stem Cells Translational Medicine however, might offer some hope that at least a regenerative therapy may be developed.


The researchers performed a double-blind, placebo-controlled study in which they gave children with Cerebral Palsy an intravenous infusion of autologous cord blood (the child’s own cord blood). They wanted to test whether cord blood cells may facilitate repair in the brains of these children. The results suggest that “when adequately dosed”, “an intravenous infusion of autologous umbilical cord blood improves whole brain connectivity and motor function in young children with Cerebral Palsy”. There was “a significantly greater increase” in Gross Motor Function Measure Scores in the group with children who received the adequate dose. Furthermore, MRI scans showed an “increase in both normalized total brain connectivity and changes in the sensorimotor network, including the pre- and post-central gyri, deep gray matter, and brainstem”. Although further research is definitely necessary, these findings can be considered groundbreaking and might open up important new horizons for future treatment of young children with Cerebral Palsy.

* * *

Literature

Kakooza-Mwesige, A. et al. (2017). Prevalence of cerebral palsy in Uganda: a population-based study. The Lancet, 5:1275-1282. See: http://www.thelancet.com/journals/langlo/article/PIIS2214-109X(17)30374-1/fulltext

National Institute for Health and Care Excellence (2017). Cerebral palsy in under 25s: assessment and management. See: http://bit.ly/2ys8ki0

National Institute for Health and Care Excellence (2017). Identifying and diagnosing cerebral palsy in under 25s - Interactive flowchart. See: http://bit.ly/2zuwHzx

Movie American Institute of Health (NIH), demonstration video. See: https://www.youtube.com/watch?time_continue=1&v=Roaxd65yGvo

Rosenbaum, P. et al. (2007) A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl 109:8-14. See: http://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2007.tb12610.x/pdf

Surveillance of Cerebral Palsy in Europe (SCPE), (2000). Surveillance of Cerebral Palsy in Europe: a collaboration of cerebral palsy surveys and registers. Developmental medicine and child neurology. Developmental Medicine & Child Neurology 2000, 42: 816–824. See: http://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2000.tb00695.x/pdf

Sun, J. M.,et al. (2017). Effect of Autologous Cord Blood Infusion on Motor Function and Brain Connectivity in Young Children with Cerebral Palsy: A Randomized, Placebo-Controlled Trial. STEM CELLS Translational Medicine. doi:10.1002/sctm.17-0102

Website SCPE, see: http://www.scpenetwork.eu/

CDC on Cerebral Palsy. See: https://www.cdc.gov/ncbddd/cp/causes.html

Photo Credits

Photo 1: CCBY Exceed Worldwide Flickr. See: https://flic.kr/p/2iKxjZ

Photo 2: CCBY: Allison Stillwell Young, Flickr. See: https://flic.kr/p/2D2D68 Photo 3: CCBY American National Institute of Health, via: http://www.dailymail.co.uk/health/article-5067289/Robotic-suit-helps-kids-cerebral-palsy-walk-upright.html

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