Diagnosis
The first step is to decide if the seizures are from a partial (focal) epilepsy,coming from a small
region of brain, or a generalized epilepsy, in which the entire brain is involved from the beginning of
the seizure. Partial and generalized epilepsies differ in causes and treatments, so making this
distinction is important. Because seizures rarely occur in front of the doctor, a careful description
from the patient, family members, or caretakers is extremely important. The presence of a clear
warning for the seizure, movements on one side of the body or head turning to one side are
indicators of focal seizure onset.

The diagnosis is unfortunately not always clear from the history, particularly in individuals with
developmental disabilities. This group may have difficulty communicating any warning that they may
feel. Tn addition, they are more likely to have multiple seizure types, making diagnosis more
difficult. The electroencephalogram (EEG), which measures brain electrical activity, is a critical test
in assessing epilepsy. Although recording a seizure on EEG can make a definative diagnosis,
seizures are unlikely to happen during a routine outpatient test. The brain produces specific
electrical abnormalities, called spikes or sharp waves, which occur in between seizures. These EEG
abnormalities can help us to determine whether the seizures begin in a focal or generalized fashion,
and in some cases may allow classification into a specific type of epilepsy. When a routine
outpatient test does not show epileptic abnormalities, other melhods may be helpful, such as
performing a prolonged (multi-hour) sleep-deprived EEG, or 24-hour ambulatory EEG, in which a
pnrtable recorder allows the patient to be recorded at home.

When the diagnosis of seizure type remains in doubt, or the seizures do not  respond well to
medication, inpatient video-EEG testing may be performed. Video-EEG  involves a hospital stay of
several days, during which antiepileptic medication may be  reduced or eliminated. The goal is to
allow seizures to occur in a protected environment,  so that a more precise diagnosis can be made.
EEG is recorded 24 hours a day, and the  patient is videotaped to capture the behavioral changes
and body movements that occur during seizures for later analysis. The results of video-EEG testing
may show that the original diagnosis of epilepsy type was wrong, and allow a change to more
effective medications, or that the patient may be a candidate for alternative therapies such as brain
surgery. In many cases, it turns out that the behavior in question was not an epileptic seizure at all,
even in people who also have true epileptic seizures. Such non-epileptic events can be caused by
numerous medical or psychological conditions, and are usually treatable once recognized.

The other key test in epilepsy diagnosis is imaging of the brain, which is usually best done with
magnetic resonance imaging (MRI). MRI is now capable of detecting even very small abnormalities
of the brain, such as scar tissue or areas of abnormal  brain development. Other safe, noninvasive
imaging tests include positron emission tomography {PET}, single photon emission computerized
tomography (SPECT), and magnetic resonance spectroscopy. These tests allow imaging of
different types of brain function rather than just structure, and are often used in evaluation of
patients for possible epilepsy surgery as well as research into the causes of epilepsy.

Treatment
Once the diagnosis of epilepsy type is made, treatment can be initiated or modified appropriately.
Any treatable causes of epilepsy, such as an enzyme deficiency, should certainly be treated, but this
is usually unlikely to stop seizures completely. 'I'he mainstay of treatment is antiepileptic
medication. There has been dramatic progress in medical therapy in recent years. Since 1993,
there have been five new antiepileptic  medications released, and three new forms of older
medications that allow easier dosing. There are also several new medications awaiting approval by
the Food and Drug Administration. This increase in treatment options allows much more flexibility
in designing a medication regimen to meet the individual's needs, often with fewer side effects.
Although the new drugs were initially tested as treatment for complex partial seizures, several of
them are proving quite effective for generalized epilepsy as well. These new medications are
proving particularly useful for individuals with  developmental disabilities, who often have multiple
seizure types and require multiple medications.

 Some people have seizures that are resistant to medication, despite high doses which cause side
effects. In these cases, alternative therapies should be sought. Epilepsy surgery (brain surgery to
treat seizures) has been performed for many decades, but is  becoming increasingly helpful with the
use of careful preoperative testing now available.  In appropriately selected cases, the chance of
seizure free outcomes may be 70% or higher. The most common type of epilepsy surgery is the
focal resection, in which a  small portion of brain is removed. This is most commonly done to
remove a tumor, scar or other well-localized abnormality which is causing epilepsy. Functional
hemispherectomy is a procedure in which a large portion on one side of the brain (hemisphere} is
removed, and the remainder is disconnected frorn the rest of the brain. This procedure is
performed only when there is already severe damage to one hemisphere and the other side is
relatively normal, such as in stroke, Sturge-Weber disease, or  Rasmussen's syndrome.
Callosotomy is a procedure in which the corpus callosum (the  band connecting the two sides of the
brain} is partially severed, to prevent seizure spread.  Unlike the other procedures, callosotomy is
unlikely to cure seizures, but may help  reduce severe drop attacks which can cause injury.
Epilepsy surgery can be performed effectively and safely in adults, children, and even infants. Such
surgery is best performed in specialized centers which have advanced diagnostic testing and
experienced personnel available.

The ketogenic diet is gaining increasing popularity as a treatment for epilepsy, especially in
children. This is a very abnormal diet which essentially produces a state of controlled starvation, in
which the body produces high levels of ketones. For reasons which remain unclear, ketones inhibit
seizure activity: The diet can he very effective, with approximately two-thirds of patients improving
seizure control. Working with the ketogenic diet requires a great deal of effort and dedication on
the part of parents and caretakers, as it is quite strict. Experienced nutritionists can provide a great
deal of assistance in food choices and managing the diet.

 Vagus nerve stimulation (VNS) is a new treatment for medically-resistant epilepsy in people
who are not candidates for brain surgery. VNS involves a short surgery to implant a
pacemaker-like device under thc skin, with a wire wrapped around the vagus nerve, a large nerve
in the neck. The VNS system gives intermittent electrical shocks to the vagus nerve, which then
conducts the stimulation to the brain. Although the mechanism of action remains unclear, VNS has
been shown to reduce seicure frequency significantly. Like antiepileptic medications, VNS was
originally tested in complex partial seizures, but there is an increasing number of reports of efficacy
in generalized epilepsy, particulary in patients with mental retardation and multiple seizure types.
 
 

The following cases illustrate the above points, with particular reference to patients with
deveiopmental disabilities:

1. A young woman with Rett's syndrnme (a progressive childhood disesse with loss of speech and
motor function) presented with generalized tonic-clonic seizures occurring weekly, despite high
levels of three medications. After starting one of the new antiepileptic drugs, seizures were
completely connolled for over one year.

2. A young man had complex partial seizures which had become increasingly frequent in recent
years, and were resistant to numerous medication trials. He appeared autistic, and had never
developed speech or verbal comprehension. An abnormality on skull x-ray had been detected in
childhood; but he had never had further testing. Video-EEG demonstrated all seizures to come
from the left temporal lobe region. An MRI scan showed a large, benign tumor in the same region,
which had likely been there since birth. The tumor was located near Wernicke's speech area,
explaining tlte lack of language development. Surgical removal of the tumor led to full control of
seizures using a single medication, with no side effects.

3. A young man with mental retardation underwent epilepsy surgery (focal resection) to treat
medically-resistant epilepsy. Unfortunately, seizures continued after surgery. A vagus nerve
stimulator was implanted, and stimulation adjusted over several months. During this period, seizure
frequency was reduced by 50%, and he became much more alert and verbal.

4. A young woman had Lennox-Gastaut syndrome, a condition with mental retardation and multiple
seizure types. The antiepileptic medication she used was fairly effective in controlling seizures, but
caused unpleasant side eftects including tremor, weight gain and hair loss. The use of one of the
new antiepileptic medications allowed reduction of the dose of her first medication, and
improvement in her side effects.

5. A young man had mild mental retardation and partial epilepsy of unknown cause. He had
repeated episodcs of status epilepticus, despite being on high levels of two antiepileptic
medications. During his most recent, very severe episode of status epilepticus, it was recognized
that his chronically high blood ammonia level represented a genetic enzyme deficiency that is often
exacerbated by one of his medications. The status epilepticus; which lasted four days, finally
stopped when this medication was removed and he was given a speciai low-protein diet to treat the
enzyme deficiency.

Conclusion:
 Epilepsy is one of the most treatable chronic medical diseases. The goals of "no seizures, no side
effects, no disability" may not be met in everybody, but they remain worthy targets. With currently
available treatment options, many people can benefit from reduced seizure frequency and/or
reduced side effects, resulting in improved quality of life. Comprehensive epilepsy centers provide
adult and pediatric neurologists, neurosurgeons, and other specialists who can provide help to
people with medically-resistant epilepsy, to improve both seizure control and quality of life.
Research continues into the causes and treatments of different forms of epilepsy. For those
individuals who cannot be helped with current techniques, re-evaluation every few years is
worthwhile as newer methods may prove more effective.

Address correspondence to:

Eric B. Geller, M.D.
Director, Adult Comprehensive Epilepsy Program
Saint Barnabas Institute of Neurology and Neurosurgery
Suite 415,101 Old Short Hills Rd.
West Orange, NJ 07052
(973) 243-6600, fax (973) 243-6631
 e-mail: egeller@sbhcs.com