HEALTH AND WELLNESS 1/2013
HEALTH AND WELLNESS
CHAPTER I
Chair and Department of Neurological Nursing,
Medical University of Lublin
Katedra i Zakład Pielęgniarstwa Neurologicznego,
Uniwersytet Medyczny w Lublinie
BARBARA CHMIELEWSKA, KRZYSZTOF TUROWSKI
Headaches and epilepsy – interrelationships and differences
Bóle głowy i padaczka – współzależności i odmienności
Headaches and especially migraine are associated with a number of brain psychiatric and neurologic disorders, including depression and anxiety, strokes and
epilepsies. Simultaneously both headaches and epilepsies are among the most common neurological diseases, mainly in pediatric population. Among headaches especially migraine present numerous similarities with epilepsy. These two conditions
may be related in numerous ways although the nature of this relationship is still
unclear and sometimes controversial. Both migraine and epilepsy are chronic disorders with transient paroxysmal episodes of altered brain function (consciousness)
and often with prodromal symptoms of aura (tab.1, tab.2). They both affect otherwise healthy individuals. Fits of epilepsy and migraine may be triggered by stress,
fatigue, hormonal fluctuations, light stimulation or alcohol consumption. Some of
epilepsies as well as migraine have a genetic component and they are originally
experienced between infancy and adolescence. However migraine is common (10%
prevalence) while epilepsy rare (about 1%) and prevalence of migraine is low in
childhood, peaks in adult age and decrease in old age, whereas the incidence of
epilepsy is highest in childhood and then in an old age. Clinically based hypothesis
that migraine and epilepsy are related dates back to the 19 th century, despite the fact
that W.R. Gowers in 1904 y. gave migraine a place in the borderland of epilepsy
(“near it, but not of it”) and stressed that distinction between the two conditions
might be problematic because epileptic seizures and migraine attacks might be mistaken one for the other. Gowers noticed that one disorder may develop while the
other goes on in the same individual but he did not stress that one provokes the other
[1]. However clinically well-known phenomenon that migraine-like headaches are
common in the course of seizure fits and migraine attacks may trigger epileptic
seizures resulted in distinguishing the entity presently known as migralepsy.
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Health and wellness
The term migralepsy was introduced in 1960 by Lennox and Lennox to describe
an overlapping condition wherein migraine with aura is followed by symptoms
characteristic of epilepsy. Subsequently, migralepsy defined as migraine-triggered
seizures was included in the current International Classification of Headache Disorders II in 2004 y[2].
EPIDEMIOLOGICAL INVESTIGATIONS showed the epilepsy prevalence
of 5,9% (range 1% - 17%) in the population of migraineurs greatly exceeds the general population prevalence of 0,5%. The migraine prevalence in epileptics is also
high and ranges between 8% and 23%. The relative risk for migraine in persons
with epilepsy was 2,4 for both subjects and their relatives. The risk of migraine was
elevated in both partial and generalized seizures and in both idiopathic and symptomatic epilepsies (particularly in post-traumatic epilepsies the risk was greater - 1,8,
as compared with idiopathic or cryptogenic epilepsies)[3]. Greater risk of migraine
was not related to age of epilepsy onset and seizure type. In pediatric studies, the
prevalence of epilepsy was also significantly higher than in subjects without epilepsy (82% v.52%), and children with epilepsy had a 4,5-fold increased risk of developing headaches of different types [4]. Detailed epidemiological analyses elucidated
possible association between migraine and epilepsy and showed that it is complex
and multifactorial. This association include the following relationship: 1/shared the
same underlying etiology - environmental or genetic risk factors, 2/ causally related
- one condition leading to the other and 3/ random co-occurrence of the two diseases by chance and independently in the same individual [3].
Terminological aspects of association between headache and epilepsy. It was
confirmed in multiple clinical observations that these two disorders may exist independently or epilepsy may initiate headache as well as migraine may trigger epilepsy. It is also well known that seizure and headache may be associated in certain
primary or secondary neurological syndromes as occipital epilepsies or benign
Rolandic epilepsy and inherited (e.g. neurofibromatosis) or accused (posttraumatic)
lesions of occipital lobe (tab.3). In relation to time headaches may be clinically observed as appearing before epileptic fit, during the fit or as a post-ictal phenomenon.
In more detailed descriptions these headaches are divided into two groups: 1. periictal headaches: a/ pre-ictal, b/ ictal and c/ postictal and 2. interictal headaches. Preictal headaches occur in about 5-15 % of cases, ictal in 3-5% and postictal in 1050%. Interictal headaches concern about 25-60% of cases [5] (tab 4). First of all
peri-ictal headaches, and among them ictal ones may be underestimate because of
the dramatic clinical manifestation of seizure the same. Current International Classification of Headache Disorders (ICHD-II) divides headache disorders into two
groups: primary and secondary (symptomatic). In the primary headache disorders,
the headaches does not have an identifiable cause and are divided into four categories: migraine, tension type-headache, the trigeminal autonomic cephalalgias, and a
group of headache disorders, analogous to the idiopathic epilepsies [6]. The chapter
of migraine divides the entity into six subtypes, and among the complications of
migraine it concerns migraine triggered seizures (tab.5). In general updated version
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Barbara Chmielewska, Krzysztof Turowski
Headaches and epilepsy - interrelationships and differences
of the Classification of Headache Disorders (ICHD-II) published by International
Headache Society in 2004 distinguished three specific entities of headache-related
seizures: migraine-triggered seizure (migralepsy), hemicrania epileptica and postictal headache (tab.6) [6]. This classification was lately postulated to be supplemented with the new disorder - ictal epileptic headache. Among essential criteria the
authors indicate: headache as a sole epileptic manifestation lasting minutes-days
who is ipsilateral or contralateral to lateralized ictal epileptiform discharges in EEG
as well as an evidence of epileptiform (any localized or generalized) discharges on
EEG and concomitantly with headache. Essential feature is that headacheas as well
as EEG abnormalities should resolve immediately after iv antiepileptic medication
(tab.7)[5].
CHARACTERISTICS OF HEADACHES ATTRIBUTED
TO EPILEPTIC SEIZURES
Migraine-triggered seizures or so-called migralepsy means a seizure triggered by
migraine attack (tab.5, tab.6). Depending on the time relationship migralepsy has
been considered as a form of pre-ictal headache. Migralepsy is a historical term that
describe a condition wherein migraine with typical aura of ophthalmic and autonomic symptoms (nausea and vomiting) was followed by symptoms characteristic of
epilepsy [1]. In other words migralepsy means an entity in which two separate disorders occur in succession. This term was accepted by International Headache Society in 2004. According to ICHD-II the diagnosis require migraine with aura and
seizures fulfilling criteria for one type of epileptic attack that occurs during or within
one hour after a migraine aura (tab.6). This definition sets that seizures are the sequence of specific headache type and they happen during migrainous aura. In this
sense the definition places seizures among complications of migraine. Migralepsy is
a rare condition; as yet about sixty cases and some reviews have been published.
Most of case reports have been criticized as describing complicated and unequivocal
disorders or they there in fact erroneously recognized occipital epilepsies [7].Taking
into account the current ICDH-II statements only 4% among fifty published cases
properly met criteria of migralepsy. Similar symptoms of epileptic aura (visual phenomena, headache) and essential seizure and migraine attacks may be mistaken one
for the other or they can overlap. In particular insufficiently understood symptomatology of occipital seizures may be erroneously interpreted as visual aura of migraine. Reports have even described status epilepticus in partial occipital lobe epilepsy that was interpreted as migrainous status [8,9]. It is widely postulated to revise
migralepsy as a separate disease entity. As yet this term could be taken into account
in cases when a fit starts with an ictal epileptic headache followed by a sensory or
motor partial and/or generalized seizure. Sporadically, headache per se may represent an epileptic seizure and the sole manifestation of epilepsy [9].
HEMICRANIA EPILEPTICA means an attack of hemicranial pain that occurs
synchronously with seizure of partial characteristics. Headache presents migrainous
features. This phenomenon is accompanied by ipsilateral EEG discharges [10]. According to ICHD-II classification four essential features that allow for recognition of
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hemicrania epileptica include: 1. headache lasting seconds to minutes, with feature
of migraine, 2. the patient is having a partial epilepsy, 3. headache develops synchronously to the seizure and it is ipsilateral to the ictal discharges (diagnosis requires the simultaneous onset of headache and epileptic discharge in EEG recording), 4. headache resolves immediately after the seizure (tab.6). The phenomenon of
hemicrania epileptica is rare. Detailed analysis of reports revealed that epileptic fits
presented features of status epilepticus (nonconvulsive or complex partial) and
headache (who completed immediately after the seizure) lasted several hours [9]. At
present it is suggested that ictal headache can rarely be the sole ictal epileptic manifestation, without any other associated ictal epileptic signs and then the term ictal
epileptic headache should rather be applied to describe this distinct disorder (clinical characteristics mentioned above) [5].
ICTAL EPILEPTIC HEADACHE
Even from the clinical point of view this type of headache is distinctly different
from both migralepsy and hemicrania epileptica because specific headache pattern is
not required. Not only migraine with aura, but also migraine without aura as well as
tension headache, and both idiopathic and symptomatic cases are all admitted.
Headache is the only ictal phenomenon without any other associated ictal epileptic
sign and symptoms who are recognized by International League Against Epilepsy.
This is different entity from hemicrania epileptica who demand occurrence of partial
epileptic seizure, sensory or motor [11, 12]. It is believed that this kind of headache
has an autonomic nature (i.e. cephalic pain). Ictal epileptic headache is usually orbital or manifest as discomfort that does not have a clear localization. On the other
hand ILAE classification defines, among the terms used to describe semiology of
epileptic seizures, a “headache“ as a cephalic sensation in the head that is different
from somatosensory (tingling, numbness, sense of movement) and autonomic seizures (distinct alteration of the cardiovascular, gastrointestinal or thermoregulatory
function). Cortical spreading depression seems to be connecting point between migraine and epilepsy. It has been hypothesized that cortical spreading depression and
cortical epileptic focus might trigger each other thus inducing attacks. Studies have
shown that headache attacks can originate at cortical or subcortical level, whereas
epileptic focus arises only cortically but can be subcortically modulated. The central
autonomic system have a lower threshold for epileptic activation than the network
producing focal epileptic sensory-motor symptoms. On the other words, the threshold required for the activation of cortical spreading depression (resulting in headache) is lower than that required for occurrence of epileptic seizure. In this way, the
onset of epileptic seizures may subsequently activate the cortical spreading depression. Cortical epileptic discharges (insufficient to cause typical clinical manifestation of seizure) might activate the trigemino-vascular system and this stimulation
results in migrainous headache as the sole clinical manifestation without any other
epileptic symptoms of cortical origin [13]. These rare cases of ictal headaches (in
fact - cases of autonomic epilepsy) are postulated to be separately classified as ictal
epileptic headaches [12,13]. Accordingly, cases with long lasting ictal epileptic
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Barbara Chmielewska, Krzysztof Turowski
Headaches and epilepsy - interrelationships and differences
headache episodes fulfill the criteria to be considered as autonomic status epilepticus
[14]. It is supposed that prevalence of this entity is underestimated as it is often
unrecognized, and from eighties until now was described only a dozen cases [5,10].
In patients with the complaints of migraine-like headache “ictal” EEG recording can
be helpful do determinate proper diagnosis. However is should be remembered that
EEG patterns showed no specific characteristics and both focal rhythmic activity,
lateralized and generalized spike-and wave or polyspike-and wave have been registered. The observed EEG patterns mostly included: rhythmic, high-voltage alpha
activity with spikes or high-voltage theta activity with sharp waves over occipital or
temporo-occipital region or even bilateral continuous spike and slow wave discharges [9,10,12]. In some cases photic stimulation can reveal photoparoxysmal
EEG response as well as simultaneous complaints about pulsating headache. Therefore EEG confirmation should not be a decisive criterion as in some clinically verified patients it was not possible to detect any ictal epileptiform activity. In some but
not all of these cases MR neuroimaging revealed secondary brain lesions in occipital or temporo-parieto-occipital region, and functional DWI-MR pointed restricted
diffusion in the occipital region. It is worth noting that complete remission of the
headache and of the epileptic abnormalities in most patients with presumed ictal
epileptic headache was achieved not by means of specific anti-migraine or antiheadache drugs but following intravenous administration of anti-epileptic drugsdiazepam or phenytoin (5,9). As yet this specific entity was not included neither in
the classification of the International Headache Society nor the International League
Against Epilepsy. It is suggested to include ictal epileptic headache to the current
ICHD-II classification in the group of headache-related seizures [5,9,11]. Proposed
diagnostic criteria are listed in table 7.
POSTICTAL HEADACHE is a headache who starts immediately after cessation of seizures. This the most frequent type between seizure-associated headaches
occurs in about 50% (or even in 62% of young population) of the epileptic patients
(tab.4) [15]. Post-ictal headache has been included in the current ICHD-II. Diagnostic criteria are as follows: a/ headache with features of tension-type or migraine (in
patients with migraine), b/ the patient has had a partial or generalized epileptic seizure, c/ headache develops within 3 h following the seizure, d/ headache resolves
within 72 h after the seizure (tab.6). Clinical analysis of post-ictal headaches in 372
epileptic patients revealed that 45% had experienced postictal headaches, a half of
them always had headaches and they were severe in 39% individuals. 27% of patients had independent headaches that were similar to their seizure-related headache.
Headaches lasted less than 6 h in 81% and more than 24 h in 8% and they were
throbbing in over two thirds [16]. Another analysis reported 51% of epileptic patients with postictal headache, and more frequently associated with generalized
tonic-clonic than with focal seizures. Every tenth patient also had independent migraine attacks. Postictal headaches were either uni- or bilateral troubling aches, with
visual aura, with phono- and photophobia as well as nausea or vomiting and lasted 6
to 72 hs. Interestingly, in migrainous patients headaches were similar to their migraine attacks and similarly responded to triptans [17]. While pre-ictal and ictal
headaches are relatively rare and short lasting, in contrast, post-ictal headaches are
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common and can impact on quality of life of the persons with epilepsy. Post-ictal
headache is most common with generalized clonic-tonic seizures but is also common in complex partial seizures and less common with simple partial seizures [16].
Post-ictal headache has been reported in patients with symptomatic epilepsy but it is
mainly recognized in idiopathic occipital epilepsies [17]. It is suggested that the
seizure discharges in the occipital lobe trigger a migraine headache through cortical,
trigeminovascular and brainstem mechanisms (similarly to the mechanism of an ictal
epileptic headache) [1,12,13,17].
REFERENCES
1. Gowers WE. The border-land of epilepsy: fints, vagal attacks, vertigo, migraine,
sleep symptoms, and their treatment. Chapter V. Philadelphia, P. Blackinston’s
Son & Co, 1907.
2. Kasteleijn-Nolst Trenite D, Parisi P. Migraine in the borderland of epilepsy:
”Migralepsy” an overlapping syndrome of children and adults? Epilepsia
2012,53 (suppl 7), 20-25.
3. Andermann E, Andermann FA. Migrain-epilepsy relationships: Epidemiological
and genetic aspects. In: Migraine and Epilepsy. FA Andermann, E.Lugaresi
eds.1987, p.281-291. Butterworths, Boston.
4. Bianchin MM, Londero RG, et al. Migraine and epilepsy: a focus on overlapping
clinical, pathophysiological, molecular, and therapeutic aspects. Curr Pain Headache Rep 2010,14,276-83.
5. Papetii L, Nicita F, et al. Headache and epilepsy - how are they connected? Epilepsy
&
Behavior
2012,xxx,
1-8
(htpp://dx.doi.org/10.1016/j.yebeh.2012.09.025).
6. International Headache Society (2004). The international Classification of Headache Disorders: 2nd edition. Cephalalgia 24 (suppl 1), 9-160.
7. Sances G, Guaschino E, et al. Migralepsy: a call for revision of definition. Epilepsia 2009, 50, 2487-96.
8. Panayiotopoulos CP. Visual phenomena and headache in occipital epilepsy: a
review, a systematic study and differentiation from migraine. Epileptic Disord
1999,1,205-16.
9. Belcastro V, Striano P. Migralepsy, hemicrania epileptica, post-ictal headache
and “ictal epileptic headache”: a proposal for terminology and classification revision. J Headache Pain 2011,12,289-94.
10. Isler H, et al. Hemicrania epileptica: a synchronous ipsilateral ictal headache
with migraine features. In: Andermann F, Lugaresi E (eds). Migraine and epilepsy. Butterworth, Boston, pp249-63.
11. Parisi P, Striano P, et al. “Ictal epileptic headache”; recent concepts for new
classification criteria. Cephalagia 2012,32,723-4.
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Headaches and epilepsy - interrelationships and differences
12. Parisi P. Why is migraine rarely, and not usually, the sole ictal epileptic manifestation? Seizure 2009,18,309-312.
13. Kastelejn-Nolst Trenite DGA, Verotti D, et al. Headache, epilepsy and photosensitivity: how are they connected? J Headache Pain 2010,11,469-76.
14. Ferrie CD, Caraballo R, et al. Autonomic status epilepticus in Panayiotopoulos
syndrome and other childhood and adult epilepsies: a consensus review. Epilepsia 2007,48,1165-72.
15. Verotti A, Copolla G, et al. Peri-ictal and inter-ictal headaches in children and
adolescents with idiopathic epilepsy: a multicenter cross-sectional study. Childs
Nerv Syst 2011,27,1419-23
16. Schacter SC, Richman K, et al. Self-reported characteristic of postictal headaches. J Epilepsy 1995,8,41-3.
17. Schon F, Blau JN. Post epileptic headache and migraine. J Neurol Neurosurg
Psychiatry 1987,50,1148-52.
Table 1. Significant clinical features of migraine and epilepsy
Feature
Consciousness
Duration
Onset
EEG
Migraine
clear
hours
gradual
nonspecific abnormalities
Epilepsy
clouded
minutes
sudden
ictal patterns, spikes,
sharp waves
Table 2. Characteristics of aura in migraine and prodromal symptoms in
epilepsy
Symptom
Duration
Automatisms
Gastric
Visual
Déjà vu
Paresthesias
Migraine
> 15 min
unusual
nausea
positive/negative
rare
common (>5-60 min)
Consciousness
preserved
Epilepsy
< 1 min
present
epigastric sensation
complex phenomenon
common
common ( secondsminutes)
altered during seizure
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Table 3. Migraine and epilepsy relationship
1. Coexisting epilepsy and migraine increased prevalence, occur together, independent attacks
2. Migralepsy (migraine induced epilepsy) seizures triggered by migraine aura
3. Epilepsy - induced headache headache as a part of ictus or postictal period
4. Primary epilepsy - migraine syndromes (features of both disorders) occipital
epilepsies benign Rolandic epilepsy
5. Secondary epilepsy-migraine syndromes occur together, common underlying cause (mitochondrial disorders, arteriovenous malformations of occipital
lobe, neurofibromatosis)
Table 4. Frequency of seizure - related headaches
Peri - ictal headaches:
Pre-ictal (5-15%)
Ictal
(3-5%)
Post-ictal (10-50%)
Inter - ictal headaches (25-60%)
Table 5. ICHD-II classification of migraine
1. Migraine
1.1. Migraine with aura
1.2. Migraine without aura
1.3. Childhood periodic syndromes that are commonly precursor of migraine
1.4. Retinal migraine
1.5. Complications of migraine
1.5.5. Migraine-triggered seizures
1.6.
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Probable migraine
Barbara Chmielewska, Krzysztof Turowski
Headaches and epilepsy - interrelationships and differences
Table 6.
criteria
ICHD-II classification of headache-related seizures with diagnostic
Migraine - triggered seizures
a. Migraine fulfilling criteria for migraine with aura
b. A seizure fulfilling diagnostic criteria for one type of epileptic attack occurs during or within 1 h after a migraine aura
Hemicrania epileptica
a. Headache lasting seconds to minutes with features of migraine
b. The patient is having a partial epileptic seizure
c. Headache develops synchronously with the seizure and it is ipsilateral to
the ictal headache
d. Headache resolves immediately after the seizure
Post-ictal headache
a. Headache with features of “tension-type headache” or in patient with migraine
b. The patient has a partial or generalized epileptic-seizure
c. Headache develops within 3 h following seizure
d. Headache resolves within 72 h after the seizure
Table 7. Proposed criteria for ictal epileptic headache (according to L. Papetti,
et al.(5))
A. Headache as a sole ictal epileptic manifestation lasting minutes, hours or
days
B. Headache that is ipsi- or contra-lateral to (lateralized) ictal epileptiform EEG
discharges ( if lateralized)
C. Evidence of epileptiform discharges (localized-any localization admitted, lateralized or generalized) on EEG, concomitantly with headache with or
without photoparoxysmal response
D. Headache resolves immediately (within a few minutes) after iv antiepileptic
medication
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ABSTRACT
Headaches and epilepsy are among the commonest brain diseases. Both migraine
and epilepsy are characterized by paroxysmal and transient alteration of brain function as well as headache, so one condition may be mistaken for the other. They can
occur separately but also comorbidity of these conditions is well known. The frequency of epilepsy among people with migraine is higher than in general population
(prevalence 5,9% versus 0,5%).The prevalence of headache and especially migraine
among patients with epilepsy is also higher than in healthy individuals (relative risk
2,4). The two disorders can parallel coexist by chance, headache may be a phenomenon of epileptic seizure or even the sole ictal manifestation as well as an essential
symptom of post-ictal period. Practical clinical observations have divided epilepsyrelated headaches into peri-ictal and interictal (in 25-60% patients). Peri-ictal headaches, directly associated with epileptic fit can be divided into pre-ictal (5-15% of
cases), ictal (3-5%) and postictal headaches (10-50%). Similarity and overlapping of
signs and symptoms of these two episodic paroxysmal disorders cause difficulties in
diagnosis and treatment in medical practice. Attempts to classify and determine the
diagnostic and therapeutic recommendation for headache - epilepsy relationships are
in progress. Current International Classification of Headache Disorders (ICHD-II,
2004) describes three entities: migraine-triggered seizure (migralepsy), hemicrania
epileptica and post-ictal headache. The latest observations postulate introducing a
new disease entity- ictal epileptic headache.
Key words: headache, epilepsy, migralepsy, hemicrania epileptica, ictal epileptic
headache
STRESZCZENIE
Bóle głowy oraz padaczka należą do najczęstszych schorzeń ośrodkowego
układu nerwowego. Wspólną kliniczną cechą zwłaszcza migreny jak i padaczek są
napadowe, przemijające zaburzenia czynności mózgu oraz bóle głowy, co stwarza
trudności rozpoznawcze. Schorzenia mogą występować niezależnie, ale
współwystępowanie jest częstym zjawiskiem. Rozpowszechnienie padaczki u osób z
migreną jest większe niż w populacji ogólnej (5,9% v.0,5%). Rozpowszechnienie
bólów głowy, szczególnie migreny, w chorujących na padaczkę również jest
większe niż u osób bez padaczki (współczynnik ryzyka - 2,4). Schorzenia te, rzadko,
mogą współwystępować równolegle, ale niezależnie od siebie u jednej osoby,
częściej ból głowy należy do objawów napadu padaczkowego lub stanowi wyłączną
i jedyną manifestację napadów padaczki. W praktyce klinicznej u chorych z
padaczką wyróżnia się bóle głowy około napadowe oraz międzynapadowe (u 2560% chorych). Bóle około napadowe mogą wystąpić jako poprzedzające właściwy
napad padaczki (5-15%), w trakcie napadu (3-5%) oraz po napadowe (10-50%).
Podobieństwo i nakładanie się na siebie klinicznych cech napadów w obu
schorzeniach niejednokrotnie stwarza trudności w ustaleniu prawidłowego
rozpoznania oraz w wyborze właściwej terapii. Próby klasyfikacji i wytyczenia
rekomendacji diagnostyczno-terapeutycznych dla zaburzeń na styku ból głowy20
Barbara Chmielewska, Krzysztof Turowski
Headaches and epilepsy - interrelationships and differences
padaczka prowadzone są od wielu lat. Obowiązująca aktualnie Międzynarodowa
Klasyfikacja Bólów Glowy (ICHD-II z r.2004) wyróżnia trzy jednostki chorobowe:
napady padaczkowe wyzwalane przez ból głowy (migralepsja), padaczkowe bóle
głowy oraz bóle głowy po napadowe. Najnowsze badania i obserwacje kliniczne
wskazują na potrzebę uaktualnienia dotychczasowej klasyfikacji nie tylko bólów
głowy, ale również napadów padaczkowych, w tym zwłaszcza uwzględnienia nowej
jednostki tj. padaczki z napadami izolowanego bólu głowy, której obraz kliniczny
spełnia kryteria padaczek o symptomatologii autonomicznej.
Słowa kluczowe: ból głowy, padaczka, migralepsia, padaczkowe bóle głowy,
padaczka z napadami izolowanego bólu głowy
Artykuł zawiera 27971 znaków ze spacjami
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