Sensory system abnormalities in childhood dystonia / dystonic cerebral palsy - are sensory networks modulated by Deep Brain Stimulation?

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Dystonia is a severely disabling and painful motor disorder in which people suffer involuntary muscle contractions causing twisting movements, abnormal postures and painful spasms. It affects at least 70 000 people in the UK (similar to Multiple Sclerosis). There are many causes but we don't yet fully understand what happens within the brain to produce these abnormal movements. Adult-onset dystonia usually involves a single part of the body, whereas childhood-onset dystonia is often widespread and so severe that people find it impossible to control their bodies. This can prevent children with relatively normal intellect from achieving adult independence. The long-term care needs of these individuals are hugely expensive to the National Health Service and society.Dystonia has no cure but symptoms can be improved by a technique called Deep Brain Stimulation (DBS). This involves using fine wires, called electrodes, to deliver electrical pulses to a specific group of nerve cells deep within the brain, called the Globus Pallidus interna (GPi). The electrodes are implanted in the brain during an operation performed by a neurosurgeon. During the surgery, we can record the activity of nerve cells in the GPi using special recording electrodes.DBS is more effective in some types of dystonia than others but we do not know why because a) we don't yet know how DBS works and b) we don't yet understand the mechanisms responsible for different types of dystonia, especially dystonia resulting from brain injury during infancy (dystonic cerebral palsy). This gap in our knowledge limits our ability to develop and apply effective therapies.Most studies investigating the mechanisms of dystonia have been in adults with genetic forms of dystonia. These studies have shown that "inhibition", the mechanism by which the body "damps down" activity within the nervous system, is reduced in people with dystonia. There is also evidence of abnormalities in the way the brain processes sensory information. Thus one possible mechanism of dystonia is that abnormal perception of sensory inputs leads to distorted or excessive movements. However, none of these mechanisms have been investigated in dystonic cerebral palsy.Studying which mechanisms are common and which differ between different types of dystonia is key to understanding the causes and improving our ability to treat this disabling condition. My own work has identified differences in the activity of GPi nerve cells between different types of dystonia and has shown that the activity of these cells is related to outcome from DBS surgery. I have also found evidence of abnormal sensory pathways in some children with dystonia, particularly in dystonic cerebral palsy. My data suggest that such sensory deficits may be linked to outcome from DBS, but more powerful markers of outcome are still needed. I plan to take this forward by investigating whether measures of sensory processing within the brain are abnormal in different types of dystonia and whether these measures relate to outcome from DBS.To investigate sensory processing I will use frequency analysis methods to detect changes in EEG (brainwave) activity in relation to a sensory stimulus and a motor task. I will compare these measures in children with different types of dystonia and in children with good and poor outcome following DBS. I will also analyse the activity of GPi cells recorded at the time of DBS surgery and compare these across different types of dystonia. Finally I will assess the pathway linking the GPi and the cortex (the outer layer of the brain) by using the implanted stimulator to evoke activity in the cortex. These data will determine whether sensory processing is abnormal in dystonic cerebral palsy and whether measures of sensory processing relate to outcome from DBS. This has important implications for predicting outcome, selecting the most appropriate candidates for surgery and in counselling patients and families.