April 2003
ACDM Technical Meeting: Think CNS
13 Nov 2002
The meeting opened with a brief introduction to CNS by Chris Cramer and Julianne Hull. They discussed the anatomy of the central nervous system and defined the two major arms of CNS in a clinical sense: neurology (the study of organic illnesses, such as Parkinsonism or epilepsy where there is a breakdown in the structure of the brain) and psychiatry (where the illness is generally not related to any structural failure of the central nervous system, for example schizophrenia or depression).
The second speaker was Dr Simon Cooper, who went into more detail to discuss one particular condition in psychiatry, that of 'panic disorder'. This is a relatively modern diagnosis, only being recognised in the last 20 years, and prior to that it was thought of as a number of diseases or even thought of as cardiac in origin. It can be defined as occurring as recurring sudden and unexpected panic attacks, as distinct from an expected attack that would suggest a phobia, and also that are not due to a direct physiological effect of a substance or condition. The symptoms are what would be expected; shortness of breath, palpitations, sweating, nausea or dizziness.
It is important in the diagnosis to differentiate from other psychiatric conditions, and this is achieved by positively excluding other diagnoses with the judicious use of general and specific rating scales. Because the presentation of the disease is not fully understood, treatments for the condition are not specific and are usually represented by anti-depressants or benzodiazepines both of which have their drawbacks.
Dr Drew Kilpatrick presented on how the nervous system is split into parts (peripheral and central), and then how the CNS is divided into the brain and spinal cord. It is important to know the anatomy of the CNS in order to understand how diseases and drugs modify its behaviour. For example, the CNS is covered by the blood-brain barrier, which normally does not allow highly charged, large or non-lipid soluble particles to cross it, but this barrier is affected by a number of things, such as trauma, infection, and hypertension. There are a many neurotransmitters that act in the brain, from the well known such as adrenaline, acetyl choline, to endorphins, nitrogen dioxide and amino acids. It is their action at synapses that implements neurotransmission, and it is the interference of one of these neurotransmissions action (in either an excitatory or inhibitory way) that is the basis for both disease and drug action. Drew then went on to discuss the project management of CNS studies, and in order to complete the studies; they are a balance of time, cost and efficiency. In order to complete studies effectively he concluded that planning was essential, and monitoring progress was required.
After lunch Sarita Soni presented on the bane of a data manager's existence, rating scales. There are literally hundreds of rating scales used for CNS diseases, ranging from a couple of data points up to many pages of questions. The scales are often completed by different people, such as investigators, subjects, carers, and it is important that Each of these scales is used to assess different aspects of a neurological or psychiatric condition, and often studies are made up of a combination of these scales.
Sarita then presented various types of scale types used in these forms, and explained the benefits and drawbacks to each. The simplest questions are simple Yes/No, which are very straightforward from a data manager's point of view, but are often inflexible in their data collection. At the other end of the spectrum are visual analogue scales, usually a 10cm line where it is marked which of the responses on the scale is most appropriate. These often give a good clinical picture, but are harder to complete.
Next, Manjit Sahdra presented on statistical aspects of clinical trials. This followed on from Sarita's presentation, in covering various types of rating scales, and how the data can be interpreted. For example, multi-item scales where the patient can record answers using pre-defined ordered responses (e.g. mild, moderate, severe), it is often difficult to detect small changes in responses over time.
Professor Keith Wesnes presented on cognitive function, and how it can be measured. He described cognitive function as the processes that allow us to function everyday (i.e. information storage and retrieval, performing actions), and separate from our drives and emotions. There are two ways of measuring cognitive function, directly by assessing task performance, and indirectly via EEG, MRI scanning or behavioural observation. Traditionally task assessment was done with paper and pen, but more recently these have been done with sitting the person being studied in front of a computer. The advantages of using technology, are that it increases the sensitivity of the responses, reduces the influence of different raters, and improves data integrity, by not having to transcribe results onto a database, and results are able to be reported quicker. The only real drawback of using computers is the unfamiliarity of some people with technology.
The final talk was from Dr Stephen Cooper, who presented an overview of schizophrenia. This disease is a disorder of thoughts, feelings or perceptions that result in a disturbance of behaviour. The presentation of the illness varies both from person to person and over time, and because of this diagnosis is difficult. Its cause is also unknown, but is thought to be a combination of genetic factors, problems with brain structure, and disturbances in neurochemical function. The condition itself was recognised over a 100 years ago, but it was not until 1911 that the term schizophrenias came into usage, and it was only in the 1960s and 1970s that the diagnosis became standardised using the DSM-IV criteria. The disease is a mixture of positive (delusions, hallucinations), and negative (loss of volition, withdrawal) symptoms. The cost of the disease is great, it is the most expensive disorder in the NHS in terms of resources required to manage it.
The early treatments for schizophrenia were poor in terms of patient response; some had up to 50% non-responders, and had major side effects such as extra-pyramidal side effects. Newer treatments; the 'atypicals' reduce the severity of side effects but the response to treatment and compliance is still not ideal.
Overall the day was enjoyable, and very informative. I would like to thank the Technical Sub-Committee for organising the event.
Andrew Green
Pharmacia