Epilepsia, 52(Suppl.
3):4551, 2011
doi: 10.1111/j.1528-1167.2011.03036.x
IMMUNITY AND INFLAMMATION IN EPILEPSY
Immuno- and antiinflammatory therapies in epileptic
disorders
*Cigdem Ozkara and yFederico Vigevano
*Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey; and
yDivision of Neurology, Bambino Gesu Childrens Hospital IRCCS, Rome, Italy
SUMMARY
Several experimental and clinical studies demon-
strated an immunologic basis for different forms
of epilepsy. A wide range of immune abnormalities
have been reported suggesting the existence of
various subtypes of epileptic syndromes with
different immunopathogenetic mechanisms. This
Several experimental and clinical studies demonstrated
an immunologic basis for different forms of epilepsy. A
wide range of immune abnormalities have been reported
suggesting the existence of various subtypes of epileptic
syndromes with different immunopathogenetic mecha-
nisms. This evidence gives rise to the development of
immunologic and immunomodulatory treatments such as
usage of steroids, plasmapheresis, and intravenous immu-
noglobulins, which will be discussed briefly in this article.
Steroids for Treatment of
Epilepsy (H. Cross, London,
United Kingdom; O. Dulac,
Paris, France)
The first report on the use of steroids in epilepsy dates
back to 1942 and was based on an earlier observation that
individuals with epilepsy had seizures provoked upon both
increased water intake and administration of antidiuretic
hormone (ADH). Working on the hypothesis that deoxy-
cortisone had effects opposite to that of ADH and, there-
fore, could have antiepileptic properties, it was used in
one patient with benefit (McQuarrie et al., 1942). In 1950,
another six patients were reported; they were treated with
adrenocorticotropic hormone (ACTH) on the rationale
Address correspondence to igdem zkara, Department of Neurol-
ogy, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
E-mail: cigdemoz@istanbul.edu.tr
Wiley Periodicals, Inc.
2011 International League Against Epilepsy
45
evidence gives rise to the development of immu-
nologic and immunomodulatory treatments such
as usage of steroids, plasmapheresis, and intrave-
nous immunoglobulins, which will be discussed
briefly in this article.
KEY WORDS: Immunological therapies, Epilepsy,
Steroids, IVIg, Plasmapheresis, ACTH.
that they were looking for a treatment that produced meta-
bolic effects similar to those of the ketogenic diet.
Although it is now known that this was most likely not the
true mechanism, a positive effect was seen in four of the
six children (Klein & Livingston, 1950). Later on, several
authors reported on the apparently serendipitous use of
ACTH in infantile spasms (IS) with resolution of both
spasms and the associated electroencephalography (EEG)
abnormality) (ORegan & Brown, 1998).
Steroid use for the treatment of epilepsy includes
ACTH, prednisolone, and prednisone (a prodrug that on
passage through the liver is converted to prednisolone)
and hydrocortisone. ACTH is not a steroid, but a 39
amino-acid polypeptide secreted by the anterior pituitary;
its release stimulates the adrenal gland to produce the
glucosteroid cortisol. Steroids are well recognized to exert
important antiinflammatory and immunosuppressive
effects. However, their side effects cannot be ignored and
may be considerably dependent on the dose and duration
used. Short-term effects include irritability, weight gain,
hypertension, glucose intolerance, gastric irritation, infec-
tions, Cushings syndrome, somnolence, and reversible
brain atrophy. Although most of these effects are revers-
ible after withdrawal of the steroids, many have the poten-
tial to become life-threatening. A 15% decrease of
cerebral blood flow in patients treated with hydrocortisone
has been reported (Chiron et al., 1993). Furthermore, the
long-term side effects of continued therapy need to be
remembered: osteoporosis, growth impairment, and adre-
nal suppression. Therefore, a sound riskbenefit estima-
tion should precede their use.
46
C. Ozkara and F. Vigevano
Steroids have been recognized to be possibly of benefit
in a variety of childhood epilepsies, but the evidence to
support this treatment is variably dependent on the syn-
drome and limited at best in most situations. Efficacy has
been demonstrated in IS by several randomized controlled
trials (RCTs). A Cochrane review regarding the treatment
of IS included 14 RCTs considering treatment with
ACTH, oral prednisolone, and vigabatrin. Overall, ste-
roids were viewed to result in faster resolution of spasms,
with the possibility of an improved developmental
outcome in a nontuberous sclerosis population (Hancock
et al., 2008). In particular, Lux et al. (2004) compared
hormonal treatment against vigabatrin; they observed re-
solution of spasms at days 1314 to be more likely in the
hormonal group. Overall outcome at 12 months was not
different in both groups, but it was suggested that develop-
mental outcome may be superior in the hormonal group
(Lux et al., 2005). No difference in efficacy was demon-
strated between ACTH and prednisolone. Vigabatrin was
more effective than hydrocortisone in the control of
spasms in patients with tuberous sclerosis complex (TSC)
(Chiron et al., 1997).
Steroids have also been reported in the treatment of
nonconvulsive status epilepticus (NCSE). However, the
problem in evaluating their benefit relies on defining the
condition to be treated at the outset. By definition, an
individual with NCSE should show a change in behavior
and responsiveness compared to the baseline, with con-
comitant EEG activity alterations showing continuous
epileptic discharges. Treatment of NCSE with steroids
can often result in dramatic beneficial effects on clinical
state and EEG, but series of such patients are lacking.
Steroids have been used in continuous spike-wave activ-
ity in slow sleep (CSWS) with cognitive regression, also
including Landau-Kleffner syndrome (LKS). In this situ-
ation, it has to be tested whether objective measures of
cognitive outcome correlate with EEG resolution. Out-
come appears to be related to steroid response and dura-
tion of CSWS/regression (Buzatu et al., 2009). However,
the frequency of relapse after discontinuation of steroids
is one of the major problems. Some authors suggest more
prolonged courses to sustain the response (Buzatu et al.,
2009).
Steroid use in other epilepsies has been more anecdotal.
There are several open-label series using steroids in drug-
resistant epilepsies with variable benefit, but groups of
patients were highly heterogeneous, their numbers small,
and positive effects lasted only short term in the majority
of cases. A Cochrane review of corticosteroids including
ACTH for childhood epilepsy other than IS retrieved three
RCTs only; two studies recruited patients with new-onset
epilepsy and neurocysticercosis, respectively, and, there-
fore, were excluded (Gayatri et al., 2009). The one
remaining study compared an ACTH 49 analog in five
children with intractable seizures against placebo using a
Epilepsia, 52(Suppl. 3):4551, 2011
doi: 10.1111/j.1528-1167.2011.03036.x
double-blind crossover design. Three children only com-
pleted the trial; four showed >50% reduction in seizures
and one showed no change (Pentella et al., 1982). A recent
study compared hydrocortisone versus deflazacort, an
analog of prednisolone, in drug-resistant epilepsy of child-
hood. Children were treated on an alternate basis with
hydrocortisone for 6 months, or deflazacort continued for
12 months. No difference in response was seen between
the two groups, although deflazacort was considerably
better tolerated (Grosso et al., 2008).
The mechanism of steroids in the treatment of epilep-
sies has been widely debated. According to the common
effects of steroids, the most likely hypothesis might be an
immunosuppressant and antiinflammatory action; sup-
pression of corticotropin-releasing hormone (CRH) levels
in the CNS are thought to have an anticonvulsant action
by decreasing neuronal excitability. However, there are
also studies proposing that steroids may have an effect on
c-aminobutyric acid (GABA)A receptors or on enhance-
ment of action of neurosteroids. Some authors suggest that
ACTH is more effective than other steroids, possibly
related to its less direct effects through activation of cen-
tral melanocortin receptors (Vigevano & Cilio, 2009).
Ganaxolone, a compound related to the neurosteroid
allopregnanolone and a positive allosteric modulator of
GABAA receptors has been evaluated in epilepsy. The
theory behind this assumes that it has similar effects on
the nervous system as steroids, but not the peripheral side-
effects. However, an initial RCT (Laxer et al., 2000) and
an open-label study (Kerrigan et al., 2000) failed to
demonstrate appreciable benefit.
Steroids have been widely used in difficult-to-treat epi-
lepsies (including the catastrophic epilepsies) in order not
only to reduce seizures, but also to rescue developmental
regression. There is limited evidence to suggest beneficial
in selected populations, becauseexcept for ISstudies
are small, open-label, uncontrolled, and performed in het-
erogeneous populations.
Future directions
Further work is needed to resolve in which patient pop-
ulations steroids should be used, using which regimen and
for how long, and how to measure defined outcomes.
Steroids and Other
Immunotherapies for Status
Epilepticus (SE) in Immunologic
Disorders (S. Shorvon, London,
United Kingdom)
Status epilepticus (SE) is a common presenting symp-
tom of a variety of immunologic conditions (Table 1).
Therapy in this area is entirely free of any high-level evi-
dence, and based on case reports and small series. In

Table 1. Conditions in which SE may occur
Hashimotos encephalopathy [or steroid-responsive
encephalopathy associated with autoimmune thyroiditis
(SREAT)]
Limbic encephalitis (LE)/autoimmune encephalopathies
Paraneoplastic
Nonparaneoplastic, associated with anti-GAD-,
anti-NMDA-receptor-, anti-LGI1-antibodies, and so on.
Vasculitis, for example SLE, Sjogrens syndrome, primary
angiitis
general, all these conditions share a number of common
features: The longer the duration, the worse is the out-
come. Treatment consists of conventional antiepileptic
drugs (AEDs) and also immunotherapy. AEDs alone often
are only partially successful andif possiblethe under-
lying disorder should also be treated. The number of con-
ditions identified is increasing, and immunologic therapy
should probably be started in all cases of refractory SE of
unknown cause.
Hashimotos encephalopathy (HE)
This disorder is the longest recognized autoimmune
encephalopathyfirst explicitly described in 1966 (Brain
et al., 1966). There have been three larger case series
(Chong et al., 2003; Chaudhuri & Behan, 2003; Castillo
et al., 2006). Most cases strikingly respond to steroids;
therefore, it has been proposed to label the condition
steroid-responsive encephalopathy associated with auto-
immune thyroiditis (SREAT) (Schuble et al., 2003).
There are almost no trials or uniform guidelines. When
treating SE in HE, AEDs alone are often unsuccessful and
additional high-dose steroids and other kind of immuno-
therapy are recommended.
The usual regimen consists of induction of remission
by intravenous methylprednisolone followed by oral pred-
nisolone at a dose of 1 mg/kg. Steroids are then slowly
tapered after 46 weeks. Relapses occur and are treated
with reexposure to methylprednisolone and steroid
sparing agents such as azathioprine, methotrexate, cyclo-
phosphamide, and intravenous immunoglobulin (IVIG).
Monitoring of therapy is on clinical not serologic grounds,
since antibody titers may not closely reflect disease activ-
ity. This condition has a tendency to recur: It was
observed that in one case in which monthly IVIG (with
rituximab) controlled all symptoms but when the IVIG
was switched to a 6-weekly regimen, seizures recurred
regularly at weeks 5 and 6 (Shorvon S, personal communi-
cation).
Encephalopathy associated with NMDA-receptor
antibodies
This disorder is a common cause of SE, and may
account for many cases previously categorized as crypto-
47
Therapies in Epileptic Disorders
genic. If there is a tumor present, the neoplasm should be
urgently removed (the longer the delay and duration of
SE, the more the risk of cerebral damage). Beyond
conventional AEDs, therapy of SE consists of high-dose
steroids, plasma exchange, IVIGs, cyclophosphamide, or
rituximab.
The choice of drugs and their dosages vary in different
centers, and will depend on severity and cause of the
disorder, the clinical context, patients age, and comorbid-
ity. It is important and not only medically, but also scien-
tifically justified, that treatment is protocol-driven and
overseen by an immunologist. Immunotherapy schedules
according to the protocols used in the UCL Institute of
Neurology, London (United Kingdom) are summarized in
Table 2.
Future directions
The role of steroids in specific SE conditions, such as in
some of the newly discovered autoantibody (Ab)associ-
ated limbic encephalitis (LE) (anti-NMDA-, anti-LGI1,
anti-GABAB1-, and anti-AMPA-Abs) has to be better
defined, as well as dosage of steroids, their administration
route, and duration of therapy. It might be important that
Table 2. Immunotherapy schedules (UCL
Institute of Neurology, London (United
Kingdom)
Disorders
Nonvasculitic antibody-mediated immunologic diseasea
High-dose steroids
Plasma exchange or IVIGs
Cyclophosphamide or rituximab
Vasculitic conditions
High-dose steroids
Cyclophosphamide
Regimens
High-dose steroids
Intravenous methylprednisolone
1,000 mg for 3 days, followed by
1 mg/kg for a period (usually 6 weeks, depending
on cause/severity) and then taper
IVIG
Two courses separated by 2 weeks, each course of 0.4 g/kg over
5 days
Cyclophosphamide
Following the CYCLOPS protocol
15 mg/kg IV over 1 h (capped at 1 g)
Repeated every 2 weeks for three doses, then
Every 3 weeks (in adults <60 years with normal renal function,
with dose adjustments depending on WBC)
Rituximab
500 mg repeated 2 weeks later (750 mg/m2) and 375 mg every
three months
a
The response is better with surface antigens (e.g., VGKA,
NMDA) than with intracellular (e.g., GAD).
Epilepsia, 52(Suppl. 3):4551, 2011
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48
C. Ozkara and F. Vigevano
the still rare patients with these disorders are treated
according to predetermined protocols within studies in
order to obtain more clear and comparable data.
In refractory SE of primarily noninflammatory origin,
the role of steroid treatment has to be further investigated,
with respect to the overall riskbenefit ratio and more
specifically to the timing of administration, dosage, and
duration.
Intravenous Immunoglobulins
(G. Avanzini, Milan, Italy)
A beneficial effect of immunoglobulin (Ig) treatment of
epileptic seizures has been first suggested after the empiri-
cal observation of Pechadre et al. (1977), who reported a
decrease in frequency and severity of seizures in children
with epilepsy treated with Ig for recurrent upper respira-
tory tract infections. This report prompted further thera-
peutic attempts with Ig in intractable epilepsies: In their
review of the literature, van Engelen et al. (1994) found 24
papers published until 1993, 14 on mixed types of epi-
lepsy, nine on IS and/or Lennox-Gastaut syndrome (LGS),
and one on postencephalitic epilepsy.
Overall, a 52% mean seizure reduction and 23% remis-
sion were reported in the 368 patients who have been trea-
ted with intramuscular or, in the large majority,
intravenous (IVIG) Ig administration until 1993, with a
very large variability across the different studies. Note-
worthy, all the other studies were open-label, except one
placebo-controlled single-blind trial (Illum et al., 1990).
Moreover, the duration was too short (only in seven stud-
ies 6 months) in most studies and too small (only four
studies were carried out in a population of >20 patients).
Furthermore, the immunologic parameters were not sys-
tematically investigated.
In a later double-blind study including 43 patients with
various types of epilepsies and 18 controls with different
doses of IVIG, the responder/nonresponder ratio was
clearly higher in the treated group, but the difference was
statistically significant for the subgroup of patients with
partial epilepsy only (van Rijckevorsel-Harmant et al.,
1994). This study and the following three published more
recently confirmed the previous ones (for references see
Mikati et al., 2010).
More consistent results were reported on selected popu-
lations of patients with IS and/or LGS, LKS, and epilep-
sies with CSWS, Rasmussen encephalitis (RE), and other
types of paraneoplastic and nonparaneoplastic autoim-
mune encephalitis currently defined as limbic encephalitis
(see reviews in: Villani & Avanzini, 2002; Villani et al.,
2008; Elovaara et al., 2008; Mikati et al., 2010; Vincent
et al., 2010). Notably, the involvement of immune-medi-
ated mechanisms is demonstrated for RE and limbic
encephalitis and hypothesized for IS, LGS, and LKS.
Intravenous Ig might have an immunorestorative effect by
Epilepsia, 52(Suppl. 3):4551, 2011
doi: 10.1111/j.1528-1167.2011.03036.x
altering the kinetics of expression of disease-related auto-
Abs (Dietrich et al., 1992). Alterations of immunologic
and inflammation markers have been correlated with the
clinical IVIG effect; however their interpretation is equiv-
ocal and interferences of different factors (e.g., AEDs)
cannot be ruled out.
The use of IVIG in association with steroids is recom-
mended as a first-line therapy in late-onset RE and as a
third-line therapy in childhood-onset RE (Granata et al.,
2003). The suggested dosing scheme is to start with three
to five consecutive infusions of 0.4 g/kg/day and to pro-
ceed with a monthly dose of 0.42.0 g/kg distributed over
15 consecutive days (Bien et al., 2005).
Although in other types of epilepsies the pathogenetic
role of immune-mediated mechanisms is less clear, all the
studies with IVIG concur in demonstrating a beneficial
effect in a substantial percentage of pharmacoresistant
patients, supporting the experimental evidence of the role
played by inflammatory and immunologic mechanisms in
epilepsy (Vezzani & Granata, 2005; Vezzani et al., 2011).
Indeed, the recently published guidelines of the European
Federation of Neurological Societies (EFNS) include
drug-resistant epilepsy of childhood among the 12 neuro-
logic disorders where IVIGs are indicated (Elovaara et al.,
2008). The recommended therapeutic scheme is similar to
the one for RE (0.4 g/kg for 5 days at 4-week intervals fol-
lowed by monthly maintenance).
The treatment is usually well tolerated, the most fre-
quent adverse effect being headache that occurred in
30% of the patients. In 4% of the cases, however, severe
adverse events (thrombosis of the jugular vein, allergic
reaction, and retrosternal pressure) were reported, lead-
ing to discontinuation of the treatment. No clinically rel-
evant changes in blood tests were observed; however,
monitoring of laboratory findings is considered to be
mandatory.
Future directions
The same questions and goals as listed for the appli-
cation of steroids might apply for the use of IVIGs as a
treatment in epilepsy syndromes with a very likely, pos-
sible, or probable autoimmune cause. Because treatment
with IVIGs is resource and financially demanding, ques-
tions about optimal duration of such treatment, dosage,
and adminstration interval should be carefully evalu-
ated.
Plasma Treatment (T. Granata,
Milan, Italy)
Immune-mediated disorders are treated by corticoster-
oids, immunosuppressants, and monoclonal antibodies
(Abs). Moreover, the activity of auto-Abs can be modu-
lated by treatment with IVIGs and by plasma treatment,
which consists of the mechanical removal of Abs by

plasmapheresis (plasma exchange, PE) or by semiselec-
tive immunoadsorption (IA). The patients plasma is sepa-
rated from the cellular elements of blood by centrifugation
during PE and substituted by replacement fluid; during
IA, circulating Igs are selectively removed from the
patients plasma, which is adsorbed on-line and given back
to the patient without any replacement fluid. Plasma treat-
ment, either by PE or IA, is indicated in disorders associ-
ated with pathogenic auto-Abs, specifically in
autoimmune ion channel disorders such as myasthenia
gravis, Lambert-Eaton myasthenic syndrome, or neuro-
myotonia.
In the recent years, a growing number of epileptic disor-
ders associated with brain inflammation and potentially
pathogenic Abs have been described; these patients do not
respond, or only partially respond, to antiepileptic drugs
but have been reported to benefit from immunomodula-
tion, including plasma treatment.
The first experience using PE to treat patients with
inflammatory epilepsy dates back to 1994. Rogers and ranted to reach a consensus on the immunomodulatory
colleagues demonstrated that some rabbits immunized
with recombinant glutamate receptor subunit 3 (GluR3)
protein developed seizures and inflammatory reactions
within the CNS resembling those observed in RE, and that
some RE patients transiently benefited from PE (Rogers
et al., 1994). Since then, plasma treatment has been used
with the rationale of removing potentially pathogenic
Abs. Unfortunately, only few patients were reported to be
successfully treated by PE or IA (Andrews et al., 1996;
Antozzi et al., 1998; Thilo et al., 2009), and in no cases
was the plasma treatment proven to be effective as a long-
term therapy (Granata et al., 2003; and Villani, personal
communication on a series of five adult patients). These
disappointing results may be probably explained in light
of the recent advances in the knowledge of RE, which
indicate a pivotal role for cell-mediated immunity in the
pathogenesis of the disease. Nonetheless, given the
dramatic, albeit transient, effect of plasma treatment
(Andrews et al., 1996; Granata et al., 2003; Thilo et al.,
2009), it may still be indicated in selected conditions, for
example, in phases with acute neurologic deterioration,
SE, and in relieving seizures before starting (or in associ-
ation with) other immunomodulatory treatments.
Plasma treatment was used in a few patients with steroid
responsive encephalopathy associated with autoimmune
thyroiditis (SREAT) (also referred as Hashimotos
encephalitis) who did not benefit from corticosteroids
(Nagpal & Pande, 2004; Hussain et al., 2005).
More recently, experiences with plasma treatment have
been increasingly reported in patients with seizure dis-
orders with auto-Abs to specific neuronal proteins, such as
voltage-gated potassium channels (VGKCs), N-methyl-D-
aspartate (NMDA) receptors, and glutamic acid decarbox-
ylase (GAD) (Vincent et al., 2004; Florance et al., 2009;
Wong et al., 2010). In most case series, likely due to the
49
Therapies in Epileptic Disorders
severity of these syndromes, plasma treatment was carried
out in association with other immunotherapy (usually ste-
roids or sequential IVIGs) and the proper effect of the dif-
ferent treatments cannot be exactly specified. However,
the contribution of plasma treatment may be derived from
the analysis of the few case reports focusing on the effect
of plasma treatment alone (Mat et al., 2008; Schimmel
et al., 2009; Agrawal et al., 2010), where it was observed
that clinical improvement paralleled the reduction of the
specific circulating Abs (Irani et al., 2008, 2010; Mat
et al., 2008) and from the reported trend toward a better
outcome in patients in whom steroids were combined with
other immunotherapy, including PE (Irani et al., 2010).
Although there are no therapeutic guidelines, PE/IA
can be considered in: (1) seizure disorders with auto-
Abs to specific neuronal protein, conditions where anti-
bodies are likely to play a major role in pathogenesis
(e.g., limbic encephalitis). Given the increasing number
of patients with these disorders, proper trials are war-
therapy, and specifically on the position of plasma treat-
ment (as first-line or only in patients refractory to ste-
roids or IVIGs, and so on); (2) conditions in which the
role of humoral immunity is still undefined, but in
which removal of Abs was proven to be at least tran-
siently effective, for example, in RE; and (3) as a
research tool in selected conditions where the observa-
tion of a rapid response to Abs removal should prompt
further pathogenetic immunologic studies.
Future directions
Proper trials are warranted to reach a consensus on best
modality of immunomodulatory therapy, and specifically
on the position of plasma treatment (as first-line or only
treatment in patients who are refractory to steroids or
IVIGs, and so on). The role of humoral immunity in sev-
eral clinical conditions should be further elucidated in
order to better identify patients who will profit of plasma
treatment therapy. Further pathogenetic immunologic
studies in those patients with a rapid response to Abs
removal may help to designate candidates who are most
likely to improve on plasma treatment.
Clinical Trials with
Antiinflammatory Agents
(J. French, New York, NY, U.S.A.)
As more becomes known about the role of inflamma-
tion in the development and perpetuation of epileptic sei-
zures, there is a greater desire to introduce therapies that
can address these mechanisms. At present, a number of
existing therapies are used by clinicians, including ste-
roids, IVIGs, and PE. These therapies are used in a number
of pediatric syndromes such as LKS, CSWS, IS, and
Epilepsia, 52(Suppl. 3):4551, 2011
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50
C. Ozkara and F. Vigevano
treatment-resistant focal epilepsy. Immune-modulating
therapies are also given to patients with presumed auto-
immune encephalopathies with or without auto-Abs, some
cases of cryptogenic SE, and RE. In addition, the hypothe-
sis that inflammation may underlie or perpetuate epilepsy
more broadly, even without an autoimmune etiology,
prompted the development of novel therapeutics for
adjunctive use in treatment-resistant focal epilepsies
(http://clinicaltrials.gov/ct2/show/NCT01048255). There
is an urgent need to perform clinical trials and studies con-
firming the effectiveness of these therapies in specific
patient populations.
Trials in these disorders present substantial difficulties.
First, the underlying disorders are heterogeneous, and a
variable degree of success would be expected. Second,
because use of antiinflammatory and/or immune-modulat-
ing therapies is entrenched for some conditions and cir-
cumstances, a placebo-control study would be difficult to
perform. This issue is complicated by the sense that delay
in initiation of treatment may be detrimental. Third, the
therapies themselves are by their nature often difficult to
blind. Fourth, all these issues are compounded by the fact
that the conditions for which these treatments are used are
relatively rare, and trials would require a large number of
centers. There are very few randomized, placebo-con-
trolled trials of antiinflammatory or immune-modulatory
therapies for patients with epilepsy. Most publications
outline case series, often retrospective. A few are prospec-
tive, but they often lack properly allocated controls. Base-
line seizure rates are rarely captured. A recent survey of
http://clinicaltrials.gov, the website on which all spon-
sored trials must be listed, did not uncover any ongoing tri-
als when the words epilepsy and steroids, epilepsy and
inflammation, and seizures and corticosteroids were
searched. A recent Cochrane review of the use of ACTH
in childhood epilepsy found only one RCT, which had
recruited only five patients (Gayatri et al., 2007).
Future directions
There is a need for more rigorous assessment of both
current and novel therapies. There is no doubt that antiin-
flammatory and immune-modulatory therapies, both
existing and future, can provide a substantial benefit
to patients who otherwise have few available effective
treatments. It is hoped that well-designed clinical
research can elucidate their benefits and potential harms,
if any, thereby allowing a better perspective on risk
benefit ratio.
Additional Contributors
Giuliano Avanzini, Milan, Italy; Helen Cross, London, United King-
dom; Olivier Dulac, Paris, France; Jacqueline French, New York, NY,
U.S.A.; Tiziana Granata, Milan, Italy; Simon Shorvon, London, United
Kingdom.
Epilepsia, 52(Suppl. 3):4551, 2011
doi: 10.1111/j.1528-1167.2011.03036.x
Disclosures
None of the authors has any conflict of interest to disclose. We con-
firm that we have read the Journals position on issues involved in eth-
ical publication and affirm that this report is consistent with those
guidelines.
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