One of the main
presentations at the recent Irish Neurology Association (INA) Neurology Update
meeting in Belfast focused on when to start and cease anticonvulsant therapy
for epilepsy patients.
The presentation was delivered by Consultant Neurologist
in Beaumont Hospital, Dublin, Dr Norman Delanty. According to the definition
provided by Dr Delanty, “epilepsies” are a “group of brain disorders affecting
individuals of all age groups, of varying and often unknown cause,
characterised by recurrent unprovoked seizures, or by one unprovoked seizure
but with an ‘enduring predisposition’ to further seizures. The epilepsies may
have significant consequences in terms of educational, vocational, and
psychosocial functioning, and physical morbidity (and potential mortality)
especially in the third of patients with drug-resistant disease.”
After outlining the consequences of poorly controlled
epilepsy, Dr Delanty provided further definition of what constitutes an
“enduring predisposition” to epilepsy. Such a predisposition could be the
result of an underlying brain dysfunction, such as a learning disability;
autism; or cerebrovascular disease. It could be the result of a potentially
epileptogenic lesion that can be uncovered through neuro-imaging, or
epileptiform abnormalities seen on routine electroencephalogram (EEG).
Dr Delanty told delegates it should be remembered that
there are many people with undiagnosed epilepsy. He also said it is important
to ask whether a “first seizure” experienced by a patient is really their first
seizure.
“The convulsion is often the ‘straw that breaks the
camel’s back’ and brings the patient to medical attention,” according to Dr
Delanty.
“Following clinical assessment, if prior unrecognised,
unappreciated seizures, then the decision to start medication is usually easy.”
He said the overall risk of recurrence in those with
first seizure is 35 per cent within three-to-five years.
Dr Delanty then provided a list of issues to consider
when initiating or choosing an anticonvulstant medication.
Was it a seizure?
Was the seizure provoked or unprovoked?
Was it the first
seizure?
Are there risk
factors for epilepsy?
Is there a
recognisable underlying epilepsy syndrome?
What are the
potential consequences of further seizures?
How urgent is
treatment initiation?
Factors to consider when choosing the type of
anticonvulsant are:
Evidence from
clinical trials and post-marketing experience.
Epilepsy syndrome
and seizure type.
Seizure severity.
Seizure density.
Age and sex.
Current (and
future) reproductive intentions.
Weight.
Medication
adherence considerations.
Co-morbidities.
Cognitive profile.
Cosmetic factors.
Dr Delanty said that treatment should be individualised
considering the risk/benefit ratio of each option. These considerations
include:
The
appropriateness of drug to seizure type.
Dosage and
titration regimes.
Drug-drug
interactions.
Risk for adverse
drug reactions.
Dr Delanty then went on to describe the value of ‘rescue
therapy’, or pharmacological first aid, with medications such as buccal
midazolam and clobazam.
“All or most patients and families should be prescribed
and counselled about this,” according to the consultant neurologist.
He also pointed out the importance of advanced nurse
practitioners with regard to patient education, who must realise that such
medication needs to be taken early in the event of a seizure, while stating
that that medication prescribed should be “individualised” for each patient.
Clinicians and patients need to recognise the potential
side effects of anticonvulsants. These might be dose-related (dizziness;
nausea; fatigue); idiosyncratic or unpredictable (rash; tremor; blood dyscrasia); chronic due
to cumulative drug exposure (weight gain/loss; mood change);
teratogenic/carcinogenic effects (VPA/TPM); and adverse events due to drug
interactions (CBZ/macrolides; inducers/bone loss).
Dr Delanty noted the challenge of oligo-epilepsy, which
refers to the rare or uncommon occurrence of seizures in an individual over
their lifetime.
Again, he stated that treatment should be individualised
and that while it may be reasonable to forgo regular medication, rescue
benzodiazepines were important.
With regard to stopping anti-epileptic drugs for patients
on regular medication, Dr Delanty said “there are no hard and fast rules”. He
said any decisions need to be based on a detailed discussion between the
patient and the neurologist.
Any withdrawal off medication needs to occur “slowly”,
according to Dr Delanty. It is also important to remember, he said, there is
generally a 30-45 per cent chance of relapse for people who come off their
medication. Consideration needs to be given of what would the consequences of a
relapse be for a patient who was currently seizure free, with the impact on
driving especially important.
“If the patient is not seizure free or has significant
side effects on their quality-of-life, then the decision is easy or easyish,”
Dr Delanty said. Such patients should be put on a non-enzyme inducing agent.
However, if the patient is seizure free and has no
significant side effects and a good quality-of-life, the decision is not so
easy. These patients can either be “left as is”; have their medication withdrawn
slowly; or be put on a non-enzyme inducing agent.
Dr Delanty also pointed out that if a patient stops their
regular anticonvulsant therapy, but needs to begin therapy again at a later
date should seizure reoccur, “10 to 20 per cent will not regain easy control in
this setting and may change to drug-refractory epilepsy.”
Improvement in services
Speaking to the Medical Independent
(MI) after this talk, Dr Delanty said epilepsy care in
Ireland has significantly improved over the last number of years.
“It needs to continue to improve,” Dr Delanty said. “This
means more consultants, more nurse specialists. The difficulty is, if you ask a
lot of people, I have this impression if you go into a restaurant or a bar on a
Friday night and ask what is the population of the Republic of Ireland, lots of
people would still say four million. It is actually five million. So you have
got the increase in population, you have got an aging population. You have got
the increased risk of neurological disorders as people get older, including
epilepsy. And you have got more complicated and complex treatment regimes. All
of that puts pressure on resources. Also for ‘difficult’ epilepsy and epilepsy
in people with special needs or intellectual disability, there should be a
complex epilepsy centre, like there is in England in Chalfont, or like there is
in Glasgow in Scotland or like there is in most European countries. These are
places where people can actually be assessed in a specific complex epilepsy
centre with possibly even respite facilities for people who require them.”
Dr Delanty also referred to the promise of more precision
therapy as a result of genetic testing.
“One of the ongoing advances that I’m excited about is
the advent of clinical genomics and genomic testing and exome testing to try
and determine the molecular cause of somebody’s epilepsy or, in the setting of
a broader epilepsy with intellectual disability, the cause of the brain
dysfunction. Because we now have the wherewithal to exome sequence and come up
with a molecular cause. That is also beginning to go into the area of precision
therapeutics where if you find a molecular cause you will be able to find the
right drug for that patient.”
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