Epilepsia, 52(Suppl.

3):1217, 2011
doi: 10.1111/j.1528-1167.2011.03030.x

IMMUNITY AND INFLAMMATION IN EPILEPSY

Systemic and neurologic autoimmune disorders

associated with seizures or epilepsy
*Angela Vincent and yPeter B. Crino
*Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United
Kingdom; and yPENN Epilepsy Center and Department of Neurology, University of Pennsylvania Medical Center,
Philadelphia, Pennsylvania, U.S.A.

with cerebral calcification. The association

between type-1 diabetes mellitus (T1DM) and
epilepsy is unclear and requires more definitive
epidemiologic analysis, despite the fact that antibodies to glutamic acid decarboxylase may provide a link between the two conditions. The
association between thyroid disorders and encephalopathies, often termed Hashimotos encephalopathy, is well known but the pathogenic
significance of antithyroid antibodies in this
condition is still debated. In general, the relationships between autoimmune mechanisms and
seizures in these conditions are unclear; the
seizures are likely to be caused by a variety of
mechanisms, including ischemia, neuronal damage, and specific and nonspecific immunity.
KEY WORDS: Multiple sclerosis, Systemic lupus
erythematosus, Celiac disease, Cerebral calcification, Diabetes, Hashimotos.

SUMMARY
In this article, we review the incidence and significance of seizures in well-established autoimmune
disorders, including multiple sclerosis (MS), diabetes mellitus, celiac disease, thyroid disease,
and systemic lupus erythematosus (SLE). The
five following presentations discuss the incidence
and possible pathogenesis of epilepsies that are
found in these well-known autoimmune conditions. There is a large body of evidence describing the clinical presentation of seizures with MS
and SLE, and showing that refractory epilepsy
can complicate these already challenging disorders. However, the mechanisms involved are
complex and generally not well understood.
Neurologic syndromes, including seizure disorders, can also be a feature of celiac disease
(CD) or subclinical CD, sometimes associated

inflammation, including proinflammatory cytokines, in

epilepsy and epileptogenesis.

Epilepsy or seizures can be a feature of a number of

autoimmune or inflammatory disorders. In these conditions, the seizures may be a direct result of the primary
disease pathology or could be secondary to the proinflammatory processes that are involved. There could be specific pathogenic antibodies (Abs) in a subpopulation of
the patients that react with neuronal antigens and cause
the central nervous system (CNS) disorder. But it is also
possible that their coexistence may be purely coincidental
or reflect some genetic predisposition that is common to
the primary disease and the cause of the epilepsy. The
study of these conditions, therefore, could help in the
understanding of the role of different auto-Abs and/or

Multiple Sclerosis (P. Striano,

Genova, Italy)
Multiple sclerosis (MS) is a highly prevalent demyelinating disease that affects individuals of all ages and can
result in significant neurologic disability. It is among the
most common neurologic diseases affecting younger
(<30 years) individuals, often female, but is also found in
male individuals, generally at an older age. Approximately 200 new cases are diagnosed each week in the
United States. Diffuse clinical manifestations include
fatigue, decreased energy levels, and depression, whereas
focal neurologic deficits such as weakness, sensory loss,
bladder and bowel dysfunction, and visual loss cause
the more profound long-term sequelae. Although the

Address correspondence to Angela Vincent, Nuffield Department of

Clinical Neurosciences, University of Oxford, John Radcliffe Hospital,
Oxford, U.K. E-mail: angela.vincent@imm.ox.ac.uk
Wiley Periodicals, Inc.
2011 International League Against Epilepsy

12

13
Systemic and Neurologic Autoimmune Disorders
pathogenesis of MS has not been fully defined, there is
solid evidence that the development of demyelinating
lesions in the white matter reflects an autoimmune process.
Analysis of the lesions seen on magnetic resonance imaging (MRI) that are evident pathologically as MS plaques,
reveals inflammatory lymphocytic infiltration consistent
with active inflammation, both humoral and cellular.
Seizures were first described in MS shortly after the original definition of the disease in the late 19th century, and
are a well-described feature of the disease. Cohorts of MS
patients with seizures and epilepsy have been identified
worldwide (Engelsen & Grnning, 1997). A recent large
meta-analysis of >19,000 patients revealed that seizures
appear in approximately 25% (range 0.57.8%; Koch
et al., 2008) of MS patients and will often require medical
therapy. Seizures may occur throughout the disease course
and may be complicated by either epilepsia partialis continua or generalized tonicclonic status epilepticus. The
duration of MS symptoms prior to first seizure is generally
several years.
Tonicclonic (primary or secondary generalized) seizures account for approximately two thirds of all seizures
in MS patients. Among the partial seizures, simple partial
seizures are about twice as common as complex partial
seizures in MS, whereas in the general population, complex partial seizures occur more frequently than simple
partial seizures (Sander et al., 1990; Spatt et al., 2001; Striano et al., 2003). Unusual seizure semiologies, such as
aphasic status epilepticus and musicogenic epilepsy, have
been sometimes described.
Most typically, seizures are seen in patients with lesions
that abut the graywhite matter junction, and these lesions
may exhibit gadolinium enhancement on MRI, further
suggestive of active inflammation. However, in some
patients, no correlation with structural lesion is found.
Indeed, the variable timing of MRI relative to seizure(s) in
the majority of MRI studies of MS patients offers few data
from which to draw definitive conclusions. Electroencephalography (EEG) studies performed in MS patients
often exhibit focal slowing, spikes, and sharp waves, but
can also be normal.
Occasionally seizures are the first manifestation of the
disease. One series reported five patients with temporal
lobe epilepsy and two cases of epilepsia partialis continua
as the first clinical manifestation. Although some authors
believe that seizures are more likely to occur during
relapses (Bttner et al., 1989; Sokic et al., 2001), others
could not confirm this notion (Kinnunen & Wikstrm,
1986; Ghezzi et al., 1990; Martnez-Jurez et al., 2009).
Indeed, seizures have been observed in relapsingremitting as well as in secondary or primary progressive MS.
Given the rarity of seizures in MS, it is difficult to investigate whether seizures are a risk factor for a quicker accumulation of disability or a quicker entry into the secondary
progressive phase.

In the setting of an acute relapse, seizures are benign

and self-limiting and do not necessarily require treatment, whereas recurrent seizures unrelated to relapse
should be treated. Antiepileptic drugs (AEDs) may
aggravate some symptoms of MS, such as fatigue, vertigo, ataxia, diplopia, and cognitive slowing. AEDs with
a potential harmful impact on motor and cognitive functions should be avoided. There are no clinical trials for
treatment of epilepsy in MS patients and, therefore, no
clear recommendations can be given at this time, but a
systematic review of treatments is available (Koch et al.,
2009).
In terms of seizure pathogenesis, it has been suggested
that the edema associated with active lesions may be
responsible for seizures in MS patients. In addition, there
is clear evidence for microglial activation and enhanced
expression of tumor necrosis factor (TNF)-a-, interferon
(IFN)-b, and specific interleukins (ILs) in MS lesions.
How these proinflammatory cytokines contribute to
epileptogenesis in MS remains inconclusive, but their
roles in seizures are the subject of many current studies
(see Friedman & Dingledine, this supplement).

Systemic Lupus Erythematosus

(F. Cendes, Campinas, Brazil)
Systemic lupus erythematosus (SLE) is an autoimmune
disease that may affect any part of the peripheral nervous
system or CNS. There is predominance in women, and
overall neuropsychiatric involvement may occur in up to
75% of patients. CNS involvement may vary from subtle
signs to severe, life-threatening conditions, and the definition of neuropsychiatric involvement is difficult due to the
diffuse CNS involvement in many cases, and the lack of a
satisfactory gold standard (Afeltra et al., 2003; Appenzeller et al., 2006a).
SLE has a clear and often vexing relationship with seizures and epilepsy. In one series, of 518 consecutive
patients with SLE (follow-up 46.8 years), 88 SLE
patients (17%) had epileptic seizures, 60 (11.6%) were
considered as primary manifestation of SLE, 23 (4.4%)
were secondary acute metabolic causes, and 5 (1%) had
epilepsy prior to the diagnosis of SLE (Appenzeller et al.,
2004). The occurrence of stroke, nephritis, and the presence of immunoglobulin (Ig)G phospholipid antibodies
covaried with seizures in these patients.
EEG may show focal slowing, spikes, or sharp waves.
EEG findings showed interictal epileptic activity in all
patients with recurrent epileptic seizures, although the
majority of patients with single epileptic seizures had normal interictal EEG. Indeed, current recommendations are
that patients with antiphospholipid antibodies and single
epileptic seizure should be followed carefully, because of
the greater risk of recurrent seizures. However, most
patients with SLE who present with first epileptic seizure
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14
A. Vincent and P. B. Crino
will not need to be treated with AEDs, as only 1.3% had
recurrent, unprovoked epileptic seizures.
MRI demonstrates cerebral cortical atrophy and variable injury to the subcortical white matter seen on fluidattenuated inversion recovery (FLAIR) sequences.
Changes in white matter are not necessarily dependent on
presence of active disease but are markers of remote vasculopathy and do seem to progress over time. Interestingly, there is evidence that these effects may result in
axonal dysfunction (not always seen on structural MRI) in
patients with active SLE, independent of overt CNS manifestations, that may be reversible during periods of inactivity of disease. These structural changes can be
associated with progressive decline and the development
of focal neurologic deficits. Death was observed in 58
patients in this cohort of 519 patients during the follow-up
period. Hippocampal atrophy can predict cognitive
impairment (Appenzeller et al., 2006b) and status epilepticus was the primary cause of death in two patients, with
no other evidence of major organ involvement at the time
of death.
On one hand, there is evidence that the seizures occur in
the setting of brain lesions and damage to subcortical
white matter following vasculitic, inflammatory, or ischemic brain injury (Appenzeller et al., 2008). On the other
hand, the underlying systemic inflammatory cascades that
are activated may be sufficient to cause seizures (see
Friedman & Dingledine, this supplement), or specific antibodies to neuronal antigens may play a role in some
patients, although the evidence is inconclusive (see Colasanti et al., 2009 for review). Irrespective of the cause, seizures are part of the American Rheumatism Association
diagnostic criteria for SLE (ACR, 1999). The development and progression of a small vessel, inflammatory
vasculopathy is a hallmark of so-called lupus cerebritis
or lupus vasculopathy. As blood vessels become more
inflamed, there is diminution of blood flow to target areas
and the development of ischemia or hemorrhage. A slow
often inexorable accumulation of cortical and subcortical
ischemic injury can occur and may predispose to recurrent
seizures. In addition, cytokine effects, autoantibody-mediated lesions, choroid plexus dysfunction, and abnormal
hypothalamic-pituitary axis response have all been implicated in various studies, but the evidence is inconclusive.
Overall, seizures in SLE are diverse in semiology and
likely to be equally variable in their cause, but better biomarkers that help to distinguish between different forms
with possible implications for treatment should be sought.

Gluten and Occipital

Calcification (G. Gobbi,
Bologna, Italy)
Celiac disease (CD) is an autoimmune condition characterized by chronic inflammation in the wall of the small
Epilepsia, 52(Suppl. 3):1217, 2011
doi: 10.1111/j.1528-1167.2011.03030.x

intestine with villous atrophy due to intolerance toward

gluten, a constituent of wheat flour. The immune reaction
is triggered by ingestion of gluten, a heterogeneous mixture of glutenin and gliadin that induces an abnormal
immune response in predisposed subjects. The condition
is associated with the HLA class II gene HLA-DQ2 in
90% of CD patients, and HLA-DQ8 in 10% of cases,
strongly suggesting that CD is, as widely thought, a
primary autoimmune disease. Immune responses against
gliadin include the activation of specific T cells, with
secretion of aggressive proinflammatory cytokines
(INF-c, TNF-a, IL-1a, IL-1b, IL-2, IL-6) that are involved
in the intestinal pathology. In addition, there are both
humoral and cellular immune responses against tissue
transglutaminase (tTG), one form of which, tTG6, is
largely distributed in the CNS (amygdala, hippocampus,
cerebellum, cerebral cortex). It is possible that a primary
immune response targeting different tTG isoenzymes
might explain the different manifestations of CD.
Gastrointestinal symptoms are the predominant presenting complaint in patients with CD, but it has been
increasingly recognized that neurologic disorders, particularly cerebellar ataxia, peripheral neuropathy, dementia,
myopathy, myelopathy, and epilepsy, are not uncommon
(Cooke & Thomas-Smith, 1966; Gobbi et al., 1992). The
prevalence of these neurologic disorders in well-established CD is from 1022.5%, but there are also many
reports of neurologic manifestations in patients who do
not have gastrointestinal symptoms, but in whom the presence of antibodies to gliadin or tTG, and jejunal biopsy are
consistent with silent or latent CD (reviewed in Hadjivassiliou et al., 2010). In some patients, epilepsy with or without cerebral calcifications has been proposed to be one
such indication of silent or latent CD. Because CD may
present with malnutrition ranging from severe malabsorption to near health, nutritional deficiencies could be
responsible for the development of epilepsy and other neurologic manifestations, and cerebral calcifications could
result from chronic folic acid deficiency due to malabsorption. Alternatively, this deficiency could be due to some of
the AEDs, but AED-induced folate deficiency is rare (e.g.,
by phenytoin), and in some cases AED therapy was started
after the discovery of the calcifications.
In the case of gluten ataxia and peripheral neuropathies,
detailed postmortem reports have shown an inflammatory
process primarily involving the cerebellum and other
regions of the CNS and peripheral nerves, suggesting an
immune-mediated pathogenesis. Circulating activated T
cells may cross the intact bloodbrain barrier (BBB) and
could damage myelin or myelin-producing cells. Moreover, inflammatory cytokines or IgA deposition in blood
vessels of the brain, and the perivascular inflammatory
infiltrate, could compromise the BBB, thereby enabling
circulating antibodies to enter the CNS and to trigger CNS
involvement. In patients with epilepsy and cerebral

15
Systemic and Neurologic Autoimmune Disorders
calcifications, it was shown that 123I-IL-2 is taken up both
in the bowel and in the occipital lobe where there were calcifications. This could be due to local inflammation or to
binding to glial cells, which can express IL-2 receptors.
Cerebral calcification could also be due to chronic
immune-complexrelated endothelial inflammation (see
Signore et al., 1997). Because circulating cytokines may
have proconvulsant actions and worsen seizures (see
Friedman & Dingledine, this supplement), any or all of
these mechanisms could contribute to the seizures that
accompany this pathology.
The role of immunity toward the nervous system in CD,
and its involvement in causing epilepsy, are areas that
need clarification, both to address the cause of the neurologic disorders such as cerebellar ataxia, that are relatively
commonly associated, and the cerebral calcification and
the epilepsy that occurs. The possibility that antibodies to
tTG2 and tTG6 are specifically involved (Hadjivassiliou
et al., 2010) needs to be further investigated, and serum
and CSF levels of these or other antibodies, and cytokines,
need to be studied.

Diabetes Mellitus (A. Marson,

Liverpool, United Kingdom)
Type-1 diabetes mellitus (T1DM) is a common condition caused by autoimmune destruction of the pancreatic
islet cells. The T cellmediated process is accompanied by
auto-Abs to islet cell antigens such as glutamic acid decarboxylase (GAD) and islet cell antigen 512. Interestingly,
the presence of GAD-Abs in T1DM was first demonstrated in patients with stiff-person syndrome (SPS), a
neurologic disorder that is a rare but well known complication of diabetes, and sometimes associated with seizures.
GAD is expressed in the CNS where it is responsible for
the synthesis of c-aminobutyric acid (GABA), the main
inhibitory neurotransmitter. However, because the
enzyme GAD is intracellular, there is no reason, a priori,
to suspect antibody-mediated dysfunction of the inhibitory
neurons in the etiology of either diabetes or of SPS.
In endocrine disorders, one has to consider that seizures
could be the result of metabolic disturbance or of associated neuroinflammation/autoimmunity. Indeed, genetic
causes such as mutations in JCNJ11, or POLG1, or
MELAS, can be associated with both diabetes and generalized epilepsy; conversely, both hypoglycemia and hyperglycemia can precipitate seizures. In addition, AEDs that
cause weight gain may lead to type-2 diabetes. Here the
discussion is confined to the role of immunity in T1DM.
Seven of 518 patients with T1DM had either juvenile
myoclonic epilepsy or generalized tonicclonic seizures,
which was higher than the predicted incidence of epilepsy
(1.6 cases per 1,000) from a control population (McCorry
et al., 2006). One other large study, found a prevalence of
9 per 1,000 active epilepsy patients within a similar pedi-

atric diabetic cohort, but, in this case, a similar prevalence

in the control cohort (OConnell et al., 2008). A higher
prevalence (2.4%) was concluded from a smaller group of
patients seen in a specialist pediatric center in Italy (Mancardi et al., 2010) but with no control group for comparison. Generally speaking it seems unlikely that there is a
substantial increase in idiopathic generalized epilepsy,
and no evidence has been provided for an increase in focal
epilepsy. Unfortunately, GAD-Abs, at the least a useful
sign of increased autoimmunity, were not measured in any
of these epidemiologic studies.
There is increasing evidence that the presence of high
titers of GAD-Abs (>1,000 U/ml) is a marker for an
immune-mediated disorder. The conditions associated
with GAD-Abs include not only SPS, but also cerebellar
ataxia and a form of limbic encephalitis in which temporal
lobe epilepsy is common, and a female predominance (see
Bien and Scheffer, this supplement). In addition, individual case reports include a variety of other focal epilepsies.
The question that needs to be addressed is how often these
Abs are found in patients with typical cryptogenic or idiopathic epilepsywhether focal or generalized. Increased
incidence of GAD-Abs has been reported in a few cohorts
of patients, either including those with an autoimmune predisposition or with drug-resistant epilepsy (Peltola et al.,
2000; McKnight et al., 2005). These aspects are more fully
discussed by Bien and Scheffer, this supplement.
In conclusion, epilepsy is not a very common accompaniment of diabetes in young patients, although there might
be a modest increase in incidence. Autoimmunity to GAD
in epilepsy is beginning to be well recognized, mainly so
far in adult cases, and this needs to be subjected to more
extensive analysis. Although GAD-Abs themselves are
unlikely to be directly pathogenic, GAD-Abs may be a
marker for the presence of other, more pathogenic Abs.
Future studies need to address more carefully both the existence of GAD-Abs in epilepsy and diabetes, the presence
of Abs against extracellular determinants, and their role.

Thyroid Immunity and Hashimotos

Encephalopathy (S. Regg,
Basel, Switzerland)
Thyroid disease is another area in which the association
with epilepsy is not very clear. Thyroid hormones acting
via their transporters and specific nuclear receptors influence both the nervous system and the immune system.
Triiodothyronine (T3) influences oligodendrocyte differentiation, and hormone deprivation during development
causes cretinism (Schweizer et al., 2008; Williams, 2008).
The effects of thyroid hormones on the human immune
system are less well known (Bittencourt et al., 2007) but
include altered T-cell subsets and increased secretion
of Abs by thyroid-stimulating hormone (TSH) and
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16
A. Vincent and P. B. Crino
thyrotropin-releasing hormone (TRH). However, the main
relationship of interest is between the presence of antithyroid Abs and a severe but reversible encephalopathy.
Hashimotos thyroiditis (HT) is associated with autoAbs directed against thyroid peroxidase (TPO) or thyroglobulin (TG) associated with destruction of the thyroid
follicular cells and induces hypothyroidism. The prevalence of subclinical hypothyroidism is 48% and may
reach up to 20% in women >60 years; however, in only
very rare cases (about 200 cases reported in the literature;
Chong et al., 2003; Chaudhuri & Behan, 2003; Castillo
et al., 2006), a severe acute/subacute encephalopathy
develops and is usually referred to as Hashimotos encephalopathy (HE).
HE is broadly defined by signs and symptoms of an
encephalopathy, exclusion of other causes, and the
presence of at least elevated anti-TPO-Abs and/or other
thyroid antibodies, usually anti-TG-Abs. A recent study
(Castillo et al., 2006) suggests a more rigorous definition
involving seven criteria: (1) encephalopathy as indicated
by cognitive impairment, neuropsychiatric features,
myoclonus, generalized tonicclonic or partial seizures or
focal neurologic deficits; (2) serum antithyroid Abs as
above; (3) a euthyroid or mildly hypothyroid state (with
appropriately raised TSH levels); (4) no evidence of infectious, toxic, metabolic, or neoplastic process; (5) no evidence of specific antineuronal Abs that have been
implicated in immune-mediated encephalopathies (see
Bien and Scheffer, this supplement); (6) no clear findings
on neuroimaging; and (7) complete or near complete clinical response to steroids. It is unlikely that all of the previously reported cases would fulfill these criteria, and many
clinical laboratories do not have access to the antibody
testing required to fulfill criterion no. 5.
The patients who have been diagnosed in the past have
diverse presentations, and defining clinical or imagining
features is clearly difficult. There may be stroke-like episodes, movement disorders, migraine, or psychosis, and in
some cases with white matter lesions on MRI, the features
are more suggestive of recurrent acute demyelinating
encephalomyelitis (ADEM; Chaudhuri & Behan, 2003).
The MRI may show signs of inflammation, white matter
changes, or vasculitis, but is normal in up to half the cases;
the CSF often shows mild pleocytosis and elevated protein, but oligoclonal bands are not always present. The
EEG is almost always markedly altered, and clinically seizures are present in 7080% of patients, with status epilepticus in 1020% (Schuble et al., 2003), but the EEG
patterns and seizure-types are diverse. Histopathologic
evaluation reveals four patterns of changes in the brain:
gliosis, demyelination, spongiform transformation, or
marked vasculitis of venules only.
Despite this diversity, the patients can respond dramatically to high-dose steroids within days, and complete
recovery is usually observed after 2 months. The disorder
Epilepsia, 52(Suppl. 3):1217, 2011
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may relapse, especially after tapering steroids, but most

patients definitively remit after a few relapses. More
intensive and combined immunomodulatory treatment
with intravenous immunoglobulins, plasma exchange,
cyclophosphamide, or rituximab may be necessary in
some cases. The role of nonsteroid drugs with immunosuppressant actions like azathioprine and methotrexate
during long-term immunosuppression is not clear.
The compulsory presence of the Abs and the rapid treatment response are the main features that distinguish this
condition from the other autoimmune forms of encephalitis
(see Bien & Scheffer, 2011), but anti-thyroid Abs, and
hypothyroidism, are very common in the population, particularly in older individuals. It is very likely that in the past
this diagnosis has been given to patients with other autoimmune forms of encephalopathy who happen to have antithyroid Abs and are treatment responsive. The treatment
responses observed are not different from those found in
other antibody-mediated conditions that have recently
become recognized (see Bien & Scheffer, this supplement).
The variability in EEG findings, the lack of distinctive
MRI changes, and the variable pathologic featuressome
of which, such as spongiform transformation, are more
likely to represent Creutzfeldt-Jakob disease (Chong &
Rowland, 2006)suggest considerable heterogeneity of
the disease as previously defined and some findings are
difficult to reconcile with a reversible condition. For these
reasons, and because the Abs do not necessarily parallel
the disease course, many authors now prefer to talk about
a steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT; Schuble et al., 2003).
The role of the antithyroid Abs in HE is uncertain
(Schiess & Pardo, 2008). These Abs might cause direct
immune-mediated damage to the brain, but it seems
equally, if not more likely, that they could be an innocent
bystander or a marker for the existence of other antibodies
that are directly pathogenic. Further studies need to define
more rigorously HE or rely on SREAT, and to look
directly with current techniques for the possible pathogenic effect of the antithyroid Abs or of the presence of
other Abs that are more likely to be involved in reversible
neuronal damage.

Future Directions
There is clear evidence that both systemic and brain specific inflammatory disorders are associated with epilepsy.
Although in some disorders seizures are associated with
actual structural brain injury, in others only the inflammatory response may trigger seizures. In some patients,
specific auto-Abs may play a role. Important issues that
remain to be elucidated include defining particular inflammatory cascades that may predispose to seizures in these
conditions, identifying reliable serum biomarkers, including specific Abs that could be used to predict seizure risk,

17
Systemic and Neurologic Autoimmune Disorders
and discovering specific therapies that may target the
inflammatory response and act as antiepileptogenic
treatments.

Additional Contributors
Fernando Cendes, Campinas, Brazil; Guiseppe Gobbi, Antonella Ciriaco, and Eliana Parente, Bologna, Italy; Anthony Marson, Liverpool,
United Kingdom; Stephan Regg, Basel, Switzerland; Pasquale Striano,
Genova, Italy.

Disclosures
AV serves as a paid consultant for Athena Diagnostics and Bayhill
Therapeutics; she and the University of Oxford receive royalties and
payments for antibody tests. PBC delcares no conflicts of interest. We confirm that we have read the Journals position on issues involved in ethical
publication and affirm that this report is consistent with those guidelines.

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Epilepsia, 52(Suppl. 3):1217, 2011

doi: 10.1111/j.1528-1167.2011.03030.x