TRANSCRANIAL MAGNETIC STIMULATION

Normal brain function relies on a carefullybalanced network of excitatory and

inhibitory nerve cells. An imbalance in this system can lead to hiperexcitability of the
brain-inparticular, the cortex and consequent seizures. Seizures result from excessive firing
and synchronization of neurons within the seizure focus. This firing cannot be contained
by the surrounding inhibitory neurons and eventually leads to the impairment of the normal
functioning of this part of the brain. If the epileptic focus lies within the motor cortex,
the seizure will cause abnormal motor activity, for example, of an arm or a leg.
Subsequently, the electrical activity may spread to other parts of the brain, resulting in
more symptoms and, eventually,loss of consciousness. Treatment of epilepsy with
antiepileptic drugs (AEDs) aims to stabilize the balance of synaptic excitation and inhibition
of neurons. In some of these patients, particularly those whose seizures arise from welldefined lesions, such as hippocampal sclerosis, surgery is an alternative treatment option.
Surgery however, carries the risk of complications, and the rate of success varies. It is
therefore desirable to develop alternative forms of treatment for intractable epilepsy
HISTORY OF ELECTRICAL AND MAGNETIC STIMULATION OF THE BRAIN
About two decades ago, researchers discovered that electrical stimulation of the
motor areas of the brain through the intact scalp (transcranial electrical stimulation). (TES)
could activate motor neurons. TES also activated pain fibers in the scalp and was
therefore quite painful. it was also possible to stimulate the brain in a way similar to that
of TES, but with little or no pain. The stimulation is usually experienced as a slight,
nonpainful prick on the scalp, similar to a poke with a fingernail. The magnetic pulses, in
turn, induce a small electrical current in the brain up to 2 to 3 centimeters beneath the
scalp, depending on the stimulus intensity. When applied over the motor cortex, TMS
pulses can activate the large, fast-conducting descending motor neurons connecting the
motor cortex with the spinal cord and, eventually, the corresponding muscle. This results
in a nvitch of the corresponding muscle that can be recorded as a motor evoked potential
(MEP) by electromyography (EMG)-for example, a small hand muscle

TRANSCRANIAL MAGNETIC STIMULATION AS AN INVESTIGATIVE TOOL IN

EPILEPSY
TMS can measure a number of parameters that help assess the state of
excitabilityof the motor cortex. The motor threshold-the smallest intensity needed to
produce an EMG response (contracting muscle fibers) reflects the neuronal excitability of
motor neurons. In patients with untreated primary generalized epilepsy, the motor
threshold is lower than that in healthy subjects, suggesting that this is a reflection of

cortical hiperyerexcitability in the patients with the illness. In contrast, treatment with
AEDs has been associated with increasing motor thresholds.
COMMENTARY
Although TMS has a proven role as a research tool in epilepsy, its role as a
treatment for epilepsy is unproven. Experimental evidence shows promising effects of low
frequency TMS on epileptogenic brain regions. A well-controlled study of TMS at the
National itnstitutes of Health (NlH), however, failed to demonstrate a significant reduction
in seizure frequency. The study examined the effects of twice daily stimulation in 24 patients
for 1 week. Although the effect on seizure frequency did not reach statistical significance,
the authors believed a mild and short-lived response did occur. The effects may have been
more significant for patients with seizure foci in brain regions more accessible to the field
of the magnet
Investigators have shown that TMS activates predominantly horizontally oriented
intracortical inhibitory or facilitatory interneurons. A measurement of the effectiveness of
intracortical inhibitorymechanisms (the same mechanisms presumed to reduce seizure
spread), at least in the motor cortex, is possible using a paired-pulse technique. In this
model, a conditioning stimulus precedes the test stimulus. The interval between the
conditioning and the test stimulus determines whether the amplitude of the test stimulus
increases (facilitation) or decreases (inhibition). A differential increase in motor cortex
excitability or decreased inhibition of the affected hemisphere has been shown in patients
with focal epilepsy. Thus, TMS is a valuable noninvasive tool to assess cortical
excitability.
TRANSCRANIAL MAGNETIC STIMULATION AS A TREATMENT FOR EPILEPSY
TMS has also actively modified cortical and corticospinal excitability with trains of
stimuli, known as repetitive TMS (rTMS). rTMS produces effects that outlast the
stimulation train. Slow rTMS ( I Hertz) decreases cortical excitability in humans, similar to
the long-term depression of synaptic transmission observed, in animals after single-Hertzrange electrical stimulation. This raises the possibility that low-frequency rTMS may
influence the hyperexcitability observed in patients with epilepsy. Bolstering the "inhibitory
defenses" using low-frequency rTMS may help correct the imbalance between excitation
and inhibition thought to contribute to the generation of seizures.In experimental animals
with a low seizure threshold {low-frequency electrical stimulation elevated the seizure
threshold. In addition, a pilot study demonstrated &at low-frequency rTMS, applied over
the vertex (the crown of the head), can decrease seizure frequency in unselected patients
with intractable seizures, possibly by reducing cortical hiperexcitability.

Thus, evidence exists that low-frequency rTMS has an anticonvulsant effect, and trials
are ongoing in both the United Kingdom and the United States to assess its feasi-bility as
a treatment for epilepsy
PRECAUTIONS
TMS and rTMS have been used safely in thousands of individuals around the
world. These therapies can be harmfurl, however, in people who have a pacemaker, an
implanted medication Pump, a metal plate in the skull, or metal objects inside the eye or
skull. For example, after brain surgery or from a shrapnel wound. The effects of magnetic
stimulation on the fetus are unknown, and so we advise against its use in pregnancy.
Theoretically, rTMS can cause seizures, but this has been rare in practice and difficult to
produce on purpose, even in epilepsy patients. Since the introduction of agreed on safety
guidelines, there have been no reports of seizures. In addition to seizures, the only known
risk of rTMS is headache, which always goes away promptly using nonprescription
medication.

CONCLUSION
TMS is an exciting tool for research into the pathophysiology of epilepsy and the
mechanisms of action of anticonvulsant drugs. It can help improve our understanding of
the basic mechanisms in epilepsy and, thus, aid the development of AEDs. In addition,
evidence indicates that low-frequency rTMS may have an anticonvulsant effect, and further
study is needed. We are now studying the treatment response of patients with epilepsy to
various low-frequency rTMS protocols. Depending on the validity of the results of this
and similar studies, rTMS may develop into an alternative noninvasive treatment for
epilepsy.