Touching Lives - March 2004
The sacred disease
Epilepsy is clearly no barrier to greatness; but it is a seriously debilitating condition, which is still common throughout the world. The first descriptions of epilepsy are acknowledged to be those found on Babylonian tablets dating back to 2000BC. But it was the Ancient Greek physician Hippocrates who, in 400BC, wrote his essay ‘On the Sacred Disease’.
Until that point our ancestors associated epilepsy with possession by spirits, but Hippocrates brought the condition back down to the realm of earthly things. “I do not believe that the Sacred Disease is any more divine or sacred than any other disease, but on the contrary, has specific characteristics and a definite cause,” Hippocrates reported from Kos.
Fast forward 2,400 years to a London laboratory, and I am witnessing the first successful use of Transcranial Magnetic Stimulation (TMS) to record brain signals. Hippocrates would be impressed!
Doctors Gonzalo Alarcon, Antonio Valentin and Professor Kerry Mills are convinced that it will be possible to use TMS to provide a reliable and non-invasive diagnosis of epilepsy for patients. Action Medical Research has given the team, based at King’s College Hospital, £40,000 to validate their theories.
Early and accurate diagnosis
Dr Alarcon explains, “Around 440,000 people in the UK have epilepsy, making it the second most common neurological condition after migraine. But in about one third of patients, it is impossible to get a sound diagnosis and confirm they actually have epilepsy — especially when the condition is in its early stages. If our project is successful we think we will be able to get an earlier and more accurate diagnosis 95 per cent of the time.”
It is important to get an early diagnosis because epilepsy gets worse if untreated. Caused by the over-excitability of neurons in the brain, ^the ‘excitability’ spreads out across larger areas of the brain over time^.
An earlier diagnosis leads to earlier treatment, hopefully nipping the condition in the bud and certainly reducing the other risks associated with epilepsy, namely injuries caused from the seizure itself, such as falls. One in 20 of us will have a seizure at some point in our lives, so it is important to have a quick, reliable and non-invasive test to identify the minority who will develop long-standing epilepsy.
Currently diagnoses are made using a standard Electroencephalogram (EEG). The EEG machine is normal equipment found in every NHS hospital which measures brain activity through the patient’s scalp. The problem with the EEG is that 50 per cent of patients with epilepsy won’t show up any abnormalities. The EEG records spontaneous wavelengths for an hour or so, and the doctor will look for evidence of abnormal waves — each one representing a very tiny seizure.
“It’s just a fishing expedition really. You’re waiting for things to happen and if they don’t happen while you’re recording you miss it, and then you won’t know if the patient has epilepsy or not,” says Dr Alarcon. “So we thought ‘if epilepsy is due to excessive excitability and excessive responsiveness of the brain, we should be able to detect it by stimulating the brain ourselves’ — so that’s what we did.”
From SPES to TMS
A traditional method for identifying the region of the brain causing the seizures in confirmed epilepsy patients has been to use electrodes to monitor brain activity. These electrodes can either be on the surface of the head, or be ‘depth electrodes’ — tiny pins inserted into the brain of patients being considered for surgical treatment. The patient then has to wait in hospital until they have a spontaneous seizure, and the abnormal area of the brain can be identified.
Single Pulse Electrical Stimulation (SPES) takes this test further. Prior to their Action Medical Research award, Doctors Alarcon and Valentin pioneered SPES using the depth electrodes to stimulate the brain with small electrical currents. The response to the current gives away the health of that part of the brain, with delayed responses showing abnormalities.
Dr Alarcon continues, “SPES is a very consistent and successful way to find the area of the brain causing the problems. When we stimulate the brain it’s easier to identify abnormal reactions than with the spontaneous EEG alone. If we find delayed responses we know it’s abnormal and we can remove that area if we think there’s a chance the patient will be seizure free. But so far we’ve only used SPES with depth electrodes inside the brain.
“The aim of our project is to find a similarly reliable test that will allow us to diagnose epilepsy without us having to be invasive, or to make the patient wait in hospital until they happen to have a seizure. The only way to stimulate the brain through the skin is through magnetic pulses — so we’re using these and trying to measure the brain’s reactions.”
Back to the lab where our story starts, and the first successful use of Transcranial Magnetic Stimulation is coming to an end. Volunteer Ana Gomez doesn’t have epilepsy, but it’s essential to make sure the equipment is working properly before using it on patients.
The TMS machine creates a sudden magnetic pulse that stimulates the brain; the EEG machine then records the brain’s response. ^This seemingly simple marriage of two pieces of existing NHS equipment could be just what epilepsy sufferers and their families have been waiting for^.
The team will be selecting another 30 healthy volunteers to act as controls. Patients who are due to have SPES on the hospital ward will have the TMS prior to their admission. Then the Action Medical Research team will be able to compare the effectiveness of TMS with SPES in finding abnormal brain responses.
“We hope that the external TMS test shows up what the internal SPES test does. It would be of incalculable benefit to have a non-invasive, reliable test for epilepsy — not just in the UK, but all over the world.”
Grateful thanks go to SEARCH for their support of this grant.