My impression is that the NICE guidelines took into account the Marson
study, as precursers of this final Lancet report have been doing the
rounds for a while in the epilepsy world.
I think it's been known for some years that response to treatment
depends more on epileptic syndrome and aetiology than on number of
untreated seizures (ages ago a wonderful study from South America that
Ley Sander was involved in where they had loads of folk who'd been
having untreated seizures for years & their prognosis for seizure
control when eventually treated was just as good as those newly
diagnosed studies from King's), except possibly in certain
circumstances, such as potential kindling in mesial temporal lobe
epilepsy (controversial, I know), and of course where traumatic brain
injury secondary to seizures complicates the picture.
Reasons for treating early are mainly QOL related, staring with
reducing the likelihood of seizure-related death (I'm not sure this
study was sufficiently powered to address that) through preventing
children losing out on education & social development due to minor
seizure activity. However, if you think those things don't matter, it's
OK to wait.
My practice is the same as Jonathan's
Stephen
Professor Stephen Brown
Peninsula Medical School
Developmental Disabilities Research & Education Group
c/o Cornwall Partnership NHS Trust
Unit 10 Bodmin Business Centre
Harleigh Road
BODMIN PL31 1AH
United Kingdom
Tel: +44 (0)1208 256233 Fax: +44 (0)1208 256232
>>> Jonathan Bird <[log in to unmask]> 27/06/05 22:31 >>>
-----Original Message-----
From: [log in to unmask]
To: [log in to unmask]
Sent: Mon, 27 Jun 2005 07:59:35 +0100
Subject: RE: [Clinical question] How early to begin antiepileptic
treatment? [encl. Lancet June 2005 article]
thanks Jonathan, would you consider posting this reply to the group as
a whole? ([log in to unmask])
BW
Alex
-----Original Message-----
From: [log in to unmask] [mailto:[log in to unmask]]
Sent: 24 June 2005 22:10
To: Mitchell Alex
Subject: Re: [Clinical question] How early to begin antiepileptic
treatment? [encl. Lancet June 2005 article]
I tend to recommend AED if EEG is paroxysmal, I consider the evidence
is persuasive, but not if not, unless the Pt is v keen to prevent a
further Sz as far as poss.
Hope this helps
Best wishes
Jonathan
-----Original Message-----
From: Alex Mitchell <[log in to unmask]>
To: [log in to unmask]
Sent: Fri, 24 Jun 2005 10:29:09 +0100
Subject: [Clinical question] How early to begin antiepileptic
treatment? [encl. Lancet June 2005 article]
Dear All,
Heres a question for discussion. How often do colleagues begin
treatment
with AEDs after first seizure? My teaching was to wait until the
second
clinically significant seizure. I know the 2004 NICE guidelines state
that treatment may be started after the first seizure if any of the
following apply:
1. the individual has a neurological deficit
2. the EEG shows unequivocal epileptic activity
3. the individual and/or their family and/or carers consider the risk
of
having a further seizure unacceptable
4. brain imaging shows a structural abnormality.
However, this new study (RCT) from two week's ago suggests modestly
beneficial effects up to about 4-5 years (see figure 2 and table 2)
albeit with greater adverse effects.
If patients are told that there is a 10% lower risk of seizures over
the
next 2+ years how many would not opt to immediate treatment? I am
surpised that in this study 22% of those given immediate treatment
said
they would have preferred to have deferred treatment but only 5% of
those randomised to deferred treatment wanted immediate treatment.
Does
this fit with your clinical experience?
R
Alex
-----------------Accompanying editorial/comment
-------------------------------
The Lancet 2005; 365:1985-1986
Treatment of new-onset epilepsy: seizures beget discussion
Anne M McIntosh a b and Samuel F Berkovic a c
See Articles
When an individual presents for the first time with a single epileptic
seizure or new-onset epilepsy, we spend much time discussing whether
to
start antiepileptic medication. This complex issue involves weighing
up
medical, psychological, and sociological factors. We advise the
individual and their family that a single seizure is associated with
an
approximately 50% risk of recurrence. Seizures are associated with an
increased risk of injury, which engenders discussion about safety to
drive, swim, operate machinery, or engage in many other activities. At
some stage, the increased risk of death (albeit small) associated with
seizures should be mentioned.
On the other hand, people who have had one or two seizures generally
do
not feel "ill", and may regard the event as "one off" (which indeed it
might be). They may be unwilling to take medication because it is a
"bother", or because of side-effects. Some individuals resist
treatment
because they are unwilling to accept the diagnosis. These are not
trifling considerations. Regular antiepileptic medication is an
acknowledgment and reminder of epilepsy, a condition that still has
some
stigma attached.
Beyond the more immediate concerns, the priority is long-term control
of
seizures. A major issue is the famous aphorism derived from Sir
William
Gowers1 that "seizures beget seizures". In other words, repeated
seizures might make chronic epilepsy more likely. There are strong
experimental data for this in animal studies,2,3 but critical analysis
of human data provides little evidence to support the hypothesis.4
Indeed, limited observations of untreated populations indicate that
epilepsy remits spontaneously in a substantial proportion5,6 and drugs
may not influence outcome.7-9 Thus this issue remains debatable.
On this background, the data provided by Anthony Marson and colleagues
in today's Lancet are welcome. These investigators did a large and
adequately powered study that examined several issues associated with
starting medication at first-seizure presentation. We commend the
authors for undertaking such a large and relatively complex
multicentre
study.
Marson and colleagues' major finding is that, in this group of
patients,
delaying medication did not increase the risk of chronic epilepsy.
This
result is especially salient when considered with their other
findings.
Patients taking immediate medication reported increased (mainly minor)
adverse events, no difference in the proportion in paid work, and an
increased preference for the alternative treatment policy. Immediate
treatment did not appear to improve quality of life, although the
response to this section was about 50%. Apart from a decreased risk of
proximate seizures, the results of this study suggest there is little
to
gain in the long term from starting medications immediately. This
conclusion applies to the practical problem of starting therapy after
the first or first few seizures-it does not imply that withholding
therapy in the face of ongoing multiple seizures is appropriate.
In terms of demographics, Marson and colleagues' study population was
mainly teenagers and young adults. Whilst this age is typical of the
first-seizure patients seen by neurologists, new-onset epilepsy is
actually most common in young children and the elderly.10 Marson's
findings would probably broadly apply to these populations. However,
in
the young, there are developmental issues to consider, with known
differences between the biology of seizures in young animals compared
with mature animals.11 In the elderly, any increase in risk might have
particular importance, because the physical consequences of seizures
(ie, fractures and associated immobility) are often greater than in a
younger population. Finally, it should be acknowledged that "epilepsy"
is not a single condition. Aggressive early treatment of certain
progressive epilepsies12 might be beneficial, but this is an area for
future research.
These issues aside, Marson and colleagues' study contributes
good-quality evidence for our discussion with patients and families
about the advisability of medication. In what is often a difficult
situation, good data coupled with a clinical synthesis of the risks
and
benefits that are tailored to the patient's personal circumstances
will
contribute to optimum treatment decisions. We now need not cloud the
matter by the bogie man of "seizures begetting seizures", at least in
the context of a single or a few seizures.
We declare that we have no conflict of interest.
References
1. Gowers WR. Epilepsy and other chronic convulsive disorders: their
causes, symptoms and treatment. J&A Churchill 1881; London
2. Morrell F, Smith MC, Detoledo-Morrell L. Secondary epileptogenesis
and kindling. In: and Wyllie E, Editor, The treatment of epilepsy:
principles and practice, Lea & Febiger, Philadelphia (1993). In: and
Wyllie E, Editor, The treatment of epilepsy: principles and practice,
Lea & Febiger, Philadelphia (1993).
3. Morimoto K, Fahnestock M, Racine RJ. Kindling and status
epilepticus
models of epilepsy: rewiring the brain. Prog Neurobiol 2004; 73: 1-60.
MEDLINE | CrossRef
4. Berg AT, Shinnar S. Do seizures beget seizures? An assessment of
the
clinical evidence in humans. Clin Neurophysiol 1997; 14: 102-110
5. Watts AE. The natural history of untreated epilepsy in a rural
community in Africa. Epilepsia 1992; 33: 464-468. MEDLINE
6. Kwan P, Sander JW. The natural history of epilepsy: an
epidemiological view. J Neurol Neurosurg Psychiatry 2004; 75:
1376-1381.
MEDLINE | CrossRef
7. van Donselaar CA, Brouwer OF, Geerts AT, Arts WF, Stroink H, Peters
AC. Clinical course of untreated tonic-clonic seizures in childhood:
prospective, hospital based study. BMJ 1997; 314: 391-392. MEDLINE
8. Camfield P, Camfield C, Smith S, Dooley J, Smith E. Long-term
outcome
is unchanged by antiepileptic drug treatment after a first seizure: a
15-year follow-up from a randomized trial in childhood. Epilepsia
2002;
43: 662-663. MEDLINE | CrossRef
9. Feksi AT, Kaamugisha J, Sander JW, Gatiti S, Shorvon SD.
Comprehensive primary health care antiepileptic drug treatment
programme
in rural and semi-urban Kenya. ICBERG (International Community-based
Epilepsy Research Group). Lancet 1991; 337: 406-409. MEDLINE
10. Hauser WA. Incidence and prevalence. In: Engel JJ and Pedley TA,
Editors, Epilepsy: a comprehensive textbook, Lippincott-Raven,
Philadelphia (1998). In: Engel JJ and Pedley TA, Editors, Epilepsy:
a
comprehensive textbook, Lippincott-Raven, Philadelphia (1998).
11. Haut SR, Veliskova J, Moshe SL. Susceptibility of immature and
adult
brains to seizure effects. Lancet Neurol 2004; 3: 608-617
12. Sutula TP. Mechanisms of epilepsy progression: current theories
and
perspectives from neuroplasticity in adulthood and development.
Epilepsy
Res 2004; 60: 161-171. Abstract | Full Text | PDF (107 KB) | MEDLINE |
CrossRef
Back to top
Affiliations
a Epilepsy Research Centre, and Department of Medicine, University of
Melbourne, Melbourne, Victoria 3081, Australia
b School of Nursing, University of Melbourne, Melbourne, Victoria,
Australia
c Department of Neurology, Austin Health, Melbourne, Victoria,
Australia
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