doi: http://dx.doi.org/10.11606/issn.1679-9836.v99i2p170-181 Rev Med (São Paulo). 2020 March-April;99(2):170-81.

Update on epilepsy: literature review

Atualização em epilepsia: revisão de literatura

Lílian Lúcia de Oliveira Costa1, Erlayne Camapum Brandão2,

Luiz Márcio de Brito Marinho Segundo3

Costa LLO, Brandão EC, Marinho Segundo LMB. Update on epilepsy: literature review / Atualização em epilepsia: revisão de literatura.
Rev Med (São Paulo). 2020 March-April;99(2):170-81.

ABSTRACT: Objectives: Epilepsy is one of the most frequent RESUMO: Objetivos: A epilepsia é uma das doenças neurológicas
neurological diseases. Due to the high incidence and damages que ocorre com maior frequência. Devido à alta incidência e
caused by the lack of control of seizures, it is necessary to have prejuízos advindos da falta de controle das crises faz-se necessário
knowledge about the peculiarities of epilepsy in order to provide o conhecimento das peculiaridades da epilepsia a fim de promover
an adequate intervention for each patient. The present study aimed ao paciente a intervenção adequada. O presente estudo visou
to describe the updates on definitions, types of epilepsy, etiological descrever a atualização sobre definições, tipos de epilepsia,
classifications, diagnosis, main pharmacological and alternative classificações etiológicas, diagnóstico, principais tratamentos
treatments. Methods: This is an integrative literature review, with farmacológicos e alternativos. Métodos: Trata-se de uma revisão
a descriptive approach. A survey was conducted in the databases integrativa da literatura com caráter descritivo. Realizou-se uma
SciELO, LILACS and MEDLINE, with a complementary survey busca nas bases de dados como SciELO, LILACS, MEDLINE
in books on epilepsy and antiepileptic drugs. Results: A total of e pesquisa complementar em livros sobre epilepsia e drogas
48 articles and 6 books that were related to the objective proposed antiepiléticas. Resultados: Foram selecionados 48 artigos e 6
and described the updates on epilepsy were selected. The articles livros na pesquisa que correspondiam ao objetivo proposto. Os
analyzed were published from 2001 to 2017. Conclusions: artigos analisados equivalem aos anos de 2001 a 2017. Conclusão:
By defining the type of seizures and identifying the cause, it Por meio da definição do tipo de crise epilética e a identificação
is possible to determine the appropriate treatment, conducted da causa é possível delinear o tratamento apropriado, conduzido
according to the singularity and the response of each patient. de acordo com a singularidade e a resposta de cada paciente,
This promotes a satisfactory treatment choice and improvement promovendo dessa forma, uma escolha terapêutica satisfatória e
in quality of life, minimizing or even avoiding harm. melhoria da qualidade de vida, minimizando ou mesmo excluindo
danos.
Keywords: Epilepsy; Anticonvulsants; Seizures.
Descritores: Epilepsia; Anticonvulsivantes; Crises epiléticas.

1. Graduanda em Medicina, Centro Universitário do Planalto Central Apparecido dos Santos (UNICEPLAC) Gama - DF ORCID: http://orcid.org/0000-
0003-3530-404X. Email: [email protected].
2. Mestre em Enfermagem pela Universidade de Brasília, DF. Professora do Curso de Graduação em Enfermagem, Centro Universitário do Planalto Central
Apparecido dos Santos (UNICEPLAC) Gama - DF. ORCID: https://orcid.org/0000-0003-0672-3536. Email: [email protected].
3. Neurocirurgião do Hospital de Base do Distrito Federal - HBDF. ORCID: https://orcid.org/0000-0001-9784-0978. E mail: [email protected]
Correspondence address: Lílian Lúcia de Oliveira Costa. Quadra 03 Conjunto N Casa 16. Setor Sul Gama, Brasília, DF. CEP: 72410 –214.

170
Costa LLO, et al. Update on epilepsy: literature review.

INTRODUCTION direct result from a known or presumed metabolic disorder.

Metabolic causes refer to manifestations or biochemical

S ince the beginning of mankind, there have been

reports of epilepsy. The term was attributed the
meaning of “taken, struck, possessed” and first appeared
changes as inborn errors of metabolism. Immune etiology
is when there is evidence of immune-mediated central
nervous system inflammation, and an unknown cause is
in Greece. Due to lack of knowledge about the disease, the when the etiology of the epilepsy has not been defined6.
Greeks and several different populations have associated According to Shorvon7, there has been a greater
epilepsy with spiritual possessions, fostering a false belief focus on the classification of the seizure type rather than
and mysticism that, unfortunately, persists until today1, on the etiology, even with the etiological classification
even though Hippocrates had already described the disease established by the ILAE. There has been no specific
in one of the books of the Hippocratic school, called On distinction between the different classifications of etiology,
The Sacred Disease, dissociating it from a divine, sacred which are essential for effective treatment, assessment of
or demoniac origin, stating that the brain was responsible prognosis and clinical course.
for this affection2. Even with the definition of the cause, about 30% of
In the 19th century, with the advances in epilepsy patients do not achieve adequate seizure control
neurophysiology, epilepsy began to be seen by the with the available drug therapy, presenting refractory
scientific community as a disease of the brain. One of the epilepsy. The lack of seizure control is associated with
pioneers, John Hughlings Jackson, a British neurologist, cognitive, motor, psychological and social impairments8,9,10.
proposed an organized anatomical and physiological These factors directly affect the health and disease process
basis for the hierarchy and location of brain functions, of these individuals, leading to consequences that end up
contributing significantly to the search for treatment being the cause of new disorders. Therefore, it is necessary
and to the understanding that it was a disease and not a to know the particularities of epilepsy for an adequate
spiritual attribution, which is an aspect that still leads to intervention. This study aims to describe the updates on
discrimination and stigmatization1. epilepsy and the main pharmacological and alternative
Epilepsy is characterized by neuronal hyperactivity treatments.
and brain circuits that lead to excessive and synchronous
electrical discharges. It appears in different ways: interictal METHOD
electroencephalographic discharges, which can extend
and cause seizures and, in more severe cases, prolonged This is an integrative review of the updates on
or repeated seizures with shorter intervals, characterizing epilepsy, addressing the definitions, types, etiological
a seizure disorder3. If a seizure occurs as a result of acute classifications and pharmacological and alternative
events such as traumatic brain injury, water-electrolyte treatments published in previously selected electronic
imbalance or concomitant diseases it is not classified as databases and books on epilepsy. The databases Scientific
epilepsy, but as a provoked seizure4. Electronic Library Online (SCIELO), Latin American
The following factors are involved in the occurrence and Caribbean Health Sciences Literature (LILACS) and
of a seizure: imbalance between excitation and inhibition Medical Literature Analysis and Retrieval System Online
of the brain, related to neuronal firing and excessive action (MEDLINE) were consulted as data source, using the
potential discharge; uncontrolled neuronal membrane descriptors: Epilepsy; Anticonvulsants; Seizures.
potential and synchronization of nerve cells5. The articles selected after reading the abstracts
A seizure can start in a point in one or both followed the inclusion criteria, namely: studies addressing
hemispheres of the brain (focal seizures), or in a part that epilepsy, new definitions, classifications and treatments
encompasses the two hemispheres of the brain (generalized of epilepsy, published from 2001 to 2017. After obtaining
seizures). Focal seizures start in a focus with excessive the search results, the titles of the studies found were read
neuronal discharges and can go to both hemispheres, and those not related to the theme, not published in the
evolving into generalized seizures1,3. pre-established period of time or not available in full text
According to the classification established by the were excluded.
International League Against Epilepsy (ILAE) in 2017,
there are six etiological groups for epilepsy: genetic, RESULTS AND DISCUSSION
structural, infectious, metabolic, immune and unknown.
Genetic epilepsy is a direct result from a known or The search returned 152 articles, of which 48 were
presumed genetic mutation; structural etiology refers to used in the present study. The articles selected were those
abnormalities visible on neuroimaging studies; infectious that were directly related to the inclusion criteria and met
etiology is when an infectious process leads to epilepsy, and the established objective. To complement the research, 6
not just seizures occurring in the setting of acute infection books addressing epilepsy and antiepileptic drugs were
such as meningitis or encephalitis; metabolic epilepsy is a selected.

171
 Rev Med (São Paulo). 2020 March-April;99(2):170-81.

Incidence and prevalence of epilepsy symptoms. Use of one versus the other depends on the
desired degree of detail6.
Epilepsy is one of the most frequent neurological Focal seizures can be subdivided into aware or
diseases. It affects approximately 1% of the world impaired awareness seizures, which replace the former
population and its incidence varies according to age, classifications of simple partial and complex partial
gender, race, type of epilepsy syndrome and socioeconomic seizures, respectively. Compared to the 1981 classification,
conditions. There is a higher prevalence of epilepsy in expanded in 2010, the new ILAE 2017 eliminated the terms
developing countries compared to developed countries, simple partial, complex partial, dyscognitive, psychic and
with 1.5 to 2.0% more cases in the former11. secondarily generalized. The latter was replaced by the
Regarding the predominance of epilepsy in seizure type “focal to bilateral tonic-clonic”. New types of
developed countries, idiopathic and developmental epilepsy focal seizures were included (automatisms, behavior arrest,
are the most common among children, and degenerative hyperkinetic, autonomic, cognitive and emotional). It was
and vascular processes predominate among older adults. decided that atonic, clonic, epileptic spasms, myoclonic and
In developing countries, on the other hand, most cases are tonic seizures can be either focal or generalized6.
related to infections, parasites and traumatic brain injuries, In the expanded classification, focal seizures were
which demonstrates etiological differences3. divided into motor and non-motor onset. Motor-onset
It is estimated that, in Brazil, 340 thousand new seizures are: Automatisms, Atonic, Clonic, Epileptic
cases of epilepsy are diagnosed per year, with 1.8 million spasms, Hyperkinetic, Myoclonic and Tonic. Nonmotor
patients with active epilepsy and at least 9 million people onset seizures are: Autonomic, Behavior arrest, Cognitive,
who have had a seizure at some point in their lives4. Emotional and Sensory. Focal aware or impaired awareness
The child and adolescent age group is highlighted, seizures may optionally be further characterized by one
as epilepsy usually has a higher incidence and prevalence of the motor - onset or nonmotor - onset symptoms,
at these ages. Children under one year old are at special considering the first prominent sign or symptom, except for
risk, as the incidence of seizures can reach 5/1,000 live focal behavior arrest seizures, which have this characteristic
births in the neonatal period12. as the dominant aspect throughout the seizure. In focal
seizures, the state of awareness can be omitted when it is not
Classification of seizures, epilepsies and epilepsy known or not applicable, classifying the seizure by its motor
syndromes or nonmotor-onset characteristics. As a rule, atonic seizures
and epileptic spasms do not have specified awareness6.
Epilepsy is considered as a disease and not as a Generalized seizures are divided into motor and
disorder of the brain, as it was previously called. Epilepsy nonmotor seizures. In the expanded version, motor seizures
is now characterized by one of the following conditions: at are: Tonic-clonic, Clonic, Tonic, Myoclonic, Myoclonic-
least two unprovoked (or reflex) seizures occurring more tonic-clonic, Atonic and Epileptic spasms. Non-motor
than 24 hours apart; one unprovoked (or reflex) seizure and seizures are: (Absence) Typical, Atypical, Myoclonic and
probability of further seizures estimated at least 60% of Eyelid Myoclonia. The latter are classified as nonmotor
recurrence, after two unprovoked seizures occurring over because they are most significant as characteristics of
the next 10 years; diagnosis of an epilepsy syndrome13. absence seizures6. Seizures with eyelid myoclonia may
For the classification of epilepsy, the physician rarely have a focal onset15. The other divisions are similar
must start by classifying the type of seizure, then the type to those of the 1981 classification, with the addition
of myoclonic-atonic seizures that occurred in Doose
of epilepsy and, in many cases, it is possible to identify a
syndrome16, common in epilepsy with myoclonic–atonic
specific epilepsy syndrome. Complementing the diagnosis,
seizures, myoclonic–tonic–clonic seizures common in
the physician should attempt to identify the etiology of
juvenile myoclonic epilepsy17, myoclonic and absence
epilepsy to determine adequate treatment and prognosis14.
seizures with eyelid myoclonia, described by Jeavons18.
Seizures of unknown onset can be referred to as
Seizure types unclassified or with additional features included in the
expanded version, such as motor (tonic-clonic and epileptic
The 2017 ILAE established a revised basic and spasms) and nonmotor (behavior arrest). They are referred
an expanded classification of seizures types, dividing to as not classifiable in situations where the onset of the
them into those of focal, general or unknown onset, with crisis cannot be determined, for exemple, cases in which the
specific categories of motor and non-motor seizures that patient was asleep and it was not possible to define whether
can be added. The difference between the expanded and the onset of the tonic-clonic crisis that was in progress was
the basic classification is that the former presents specific focal. A seizure of unknown onset can later be classified as
subcategories for seizures with motor and nonmotor focal or generalized6.

172
Costa LLO, et al. Update on epilepsy: literature review.

Characterization of focal seizures In myoclonic seizures there are sudden and brief
shock-like muscle contractions that can affect facial
Cognitive crises imply impaired language or other muscles, trunk, extremities, individual muscles or groups
functions of the cognitive domain or the presence of of muscles and that can be isolated or repetitive22.
positive features such as déjà vu, hallucinations, illusions or A tonic-myoclonic seizure is followed by a tonic
perceptual distortions. Emotional seizures involve anxiety, seizure. Sometimes, a series of myoclonic spasms occur
fear, joy and other emotions, or appearance of affect without before the increase in tone6.
associated subjective emotions6. Myoclonic-atonic seizures are found mainly in
Autonomic crises are characterized by autonomic childhood epilepsies. These seizures are characterized by
phenomena, which can involve cardiovascular, myoclonic jerks in the upper limbs, usually flexed, followed
gastrointestinal, vasomotor and thermoregulatory functions. by loss of muscle tone, head-drop and knee flexion21.
Examples include palpitations, nausea, hunger, chest pain, In clonic, tonic and atonic seizures, there may be
urge to urinate or defecate, goosebumps, sexual arousal, loss of consciousness with a clonic (myoclonia), tonic
a sense of heat or cold, piloerection, pallor, tachycardia (muscle contraction) and atonic component, characterized
or bradycardia/asystole, flushing, pupillary changes and by a sudden fall to the ground3.
weeping19. In epileptic spasms there may be sudden flexion,
Hyperkinetic seizures include violent, sudden and extension or mixed flexion-extension of proximal and
pedaling movements. And behavior arrest seizures have truncal muscles, lasting 1-2 seconds, but not more than
cessation of activity as the dominant aspect throughout 2 seconds. Spasms typically occur in a series, usually
the seizure6. on wakening. Subtle forms may occur with only chin
Automatisms tend to be coordinated and repetitive movement, grimacing, or head nodding. Spasms may be
movements resembling voluntary movements. Most of bilaterally symmetric, asymmetric, or unilateral19.
the time, they are associated with impaired awareness
and subsequent amnesia. Examples are: oral automatisms Types of epilepsy
such as chewing, tooth grinding, lip pursing; manual or
pedal, with bilateral or unilateral distal components such After diagnosis of the seizure type, the next step
as fumbling, tapping, manipulating movements; gestural, is the diagnosis of the epilepsy type, which includes focal
with fumbling or exploratory movements with the hand, epilepsy, generalized epilepsy, combined generalized and
directed towards self or environment; mimetic, with facial focal epilepsy and also an unknown epilepsy group. The
expressions like fear; vocal, with screams; verbal, with main objective of this classification is to identify the types
short words or phrases; gelastic, with bursts of laughter; of seizures that are most likely to occur in a given patient,
hyperkinetic, with pedaling movements and hypokinetic, the triggers for their seizures, the prognosis, including
with arrest/decrease of ongoing motor activity20. learning difficulties, cognitive impairment, psychiatric
It should be noted that atonic, clonic, epileptic disorders, and mortality risk, and then select the treatment14.
spasms, myoclonic and tonic seizures can be either focal Focal epilepsies were defined as seizures that
or generalized6. The latter are described below. originate in only one hemisphere of the brain. They may
be more localized or widely distributed in that hemisphere
Characterization of generalized seizures and may originate in subcortical structures. Each type
of seizure would have a consistent ictal onset, with a
Tonic-clonic (grand mal) seizures are characterized preferential spread pattern, involving or not the contralateral
by sudden loss of consciousness, with tonic and subsequent hemisphere23. They can evolve into generalized seizures,
clonic contraction of the four limbs, with apnea, sphincter which occur in bilaterally distributed neural networks and
relaxation and sialorrhea21. quickly spread24. In the new 2017 ILAE classification, the
In typical absences (petit mal), the patient presents terminology for this type of seizure was replaced by focal
brief episodes of impaired awareness with minor motor to bilateral tonic-clonic seizures6.
events, oral and manual automatisms, eye-blinking, Different types of seizures may occur, including
increased or decreased muscle tone and autonomic events focal aware seizures, focal impaired awareness seizures,
with abrupt onset and termination3. focal motor seizures, focal non-motor seizures and focal
Atypical absences show less impaired awareness, to bilateral tonic-clonic seizures14.
slower onset and termination and altered muscle tone22. For a diagnosis of Generalized Epilepsy, the
Eyelid myoclonia are rapid jerks of the eyelids electroencephalogram (EEG) must show generalized
when closing the eyes, which causes rapid eye-blinking spike-wave epileptiform activity. The diagnosis is clinical,
and upward deviation of the eyes. This phenomenon supported by the finding of typical discharges on the EEG.
may appear in isolation or manifest along with very brief However, there are cases of patients with generalized
absence seizures lasting only a few seconds21. tonic-clonic seizures and normal EEG. In this situation,

173
 Rev Med (São Paulo). 2020 March-April;99(2):170-81.

there must be evidence to support the clinical diagnosis, astatic) seizures; Childhood absence epilepsy; Benign
for example, myoclonic jerks and positive family history. epilepsy with centrotemporal spikes; Autosomal -
Individuals with generalized epilepsies can have several dominant nocturnal frontal lobe epilepsy; Late onset
types of seizures, including absence, myoclonic, atonic, childhood occipital epilepsy (Gastaut type); Epilepsy with
tonic and tonic-clonic seizures14. myoclonic absences; Lennox - Gastaut syndrome; Epileptic
In relation to combined generalized and focal encephalopathy with continuous spike - and - wave during
epilepsies, the diagnosis of both types of seizures is made sleep and Landau-Kleffner syndrome.
on clinical grounds, supported by discharges in the EEG. • Adolescence – Adult: Juvenile absence epilepsy;
Ictal recordings are helpful, but not essential. Interictal Juvenile myoclonic epilepsy; Epilepsy with generalized
EEG can show both generalized spike-wave and focal tonic–clonic seizures alone; Progressive myoclonus
epileptiform discharges, but epileptiform activity is not epilepsies; EAutosomal dominant epilepsy with auditory
required for diagnosis. Common examples in which features; Other familial temporal lobe epilepsies.
both types of seizures occur are Dravet Syndrome and • Variable age of onset: Familial focal epilepsy with
Lennox-Gastaut Syndrome. The unknown category is when variable foci (childhood to adult) and Reflex epilepsies.
there is not enough evidence to characterize epilepsy as • Distinctive constellations/surgical syndromes:
focal, generalized or both, such as a patient with several Mesial temporal lobe epilepsy with hippocampal sclerosis;
symmetrical tonic-clonic seizures without focal features Rasmussen syndrome; Gelastic seizures with hypothalamic
and normal EEG recordings. These are seizures that cannot hamartoma and Hemiconvulsion-hemiplegia-epilepsy.
be clearly classified until information allows a precise • Epilepsies attributed to and organized by
diagnosis14. structural - metabolic causes: Malformations of cortical
development (hemimegalencephaly, heterotopias, etc.);
Epilepsy syndrome Neurocutaneous syndromes (tuberous sclerosis complex,
Sturge-Weber, etc.); Tumor; Infection; Trauma; Angioma;
According to the guidelines in the 2017 ILAE Perinatal or prenatal insults; Cerebrovascular accident.
Classification, after defining the type of epileptic seizure and • Epilepsies of unknown cause24.
the type of epilepsy, there is a possibility of diagnosing an The epilepsy syndromes currently classified by the
epilepsy syndrome6. An epilepsy syndrome is characterized ILAE 2017 are:
by a set of signs and symptoms that commonly occur • Idiopathic generalized epilepsies: encompass 4
together, which can be clinical (intellectual or psychiatric epilepsy syndromes, which are childhood absence epilepsy,
impairment, for example) or alterations detected in juvenile absence epilepsy, juvenile myoclonic epilepsy and
complementary exams (EEG, imaging). Electroclinical generalized tonic-clonic seizures alone (formerly known
syndromes are grouped by age of onset and remission as generalized tonic-clonic seizures on awakening, but the
(where applicable), seizure triggers, diurnal variation or term “awakening” was removed because these seizures can
even the prognosis. An epileptic syndrome will not always occur at any time of day). The “idiopathic” terminology is
have a specific correlation with an etiological diagnosis, maintained for the 4 epileptic syndromes mentioned above;
but it may have implications for the therapeutic approach14. however, one should be attentive, because, in most cases,
In the previous ILAE classification, all electroclinic these syndromes have genetic etiology, as supported by the
epilepsy syndromes were described and grouped by age of increasing recognition and discovery of the genes involved
onset24. In the current 2017 classification, syndromes were in many epilepsies. In individual cases, the term Genetic
divided into two groups: idiopathic generalized epilepsies Generalized Epilepsy may be used where the clinician is
and self-limited focal epilepsies. However, only the main comfortable with invoking a genetic etiology.
syndromes were cited in the new classification14. • Self-limited focal epilepsies: There are several
The electroclinical syndromes, arranged by age at self-limited focal epilepsies, typically beginning in
onset, as classified by the 2010 ILAE, are described below: childhood. The most common is self-limited epilepsy with
• Neonatal period: Benign neonatal seizures; centrotemporal spikes, previously called “benign epilepsy
Benign familial neonatal epilepsy; Early myoclonic with centrotemporal spikes”. Also included in this group
encephalopathy and Ohtahara syndrome. Infancy: Febrile are the self-limited occipital epilepsies of childhood. Other
seizures; Febrile seizures plus; Benign infantile epilepsy; self-limited frontal lobe, temporal, and parietal lobes
Benign familial infantile epilepsy; West syndrome; Dravet epilepsies have also been described, with some beginning
syndrome; Myoclonic epilepsy in infancy; Myoclonic in adolescence and even in adulthood14.
encephalopathy in nonprogressive disorders and Epilepsy Epilepsy syndromes that presented the term
of infancy with migrating focal seizures. “benign”, such as benign epilepsy with centrotemporal
• Childhood: Febrile seizures; Febrile seizure plus; spikes, may be associated with transient or long-lasting
Early-onset childhood occipital epilepsy (Panayiotopoulos cognitive effect14. The term “benign” was replaced by “self-
syndrome); Epilepsy with myoclonic atonic (previously limited” and “pharmacoresponsive”, as it is understood that

174
Costa LLO, et al. Update on epilepsy: literature review.

the term “benign” underestimates the consequences of the the genes of the potassium channels. In the syndrome of
disease24 “Self-limited” refers to the likely spontaneous autosomal dominant nocturnal frontal lobe epilepsy, the
resolution of a syndrome. “Pharmacoresponsive” means underlying mutation is only known in a small proportion
that the epilepsy syndrome is expected to be controlled of individuals26.
with drug therapy14. A large number of genes have been identified by
After using elements to classify the type of seizure, molecular genetics. Gene mutation is responsible for the
epilepsy and/or epilepsy syndrome, the next step is to define most frequently arising de novo epilepsies in 30-50%
the etiology of epilepsy, given its relevance for establishing of children with severe epileptic and developmental
targeted therapy and prognosis. Resource poor countries encephalopathies, the most common example being
will not always have the means to support an accurate Dravet syndrome. Understanding the phenotypic spectrum
classification. This should be taken into account, even associated with mutations of a specific gene is critical
though classification is an appropriate method6. information, since the identification of a mutation in
Positive family history and laboratory tests such as a gene, on its own, may not enable prediction of the
the detection of antineuronal antibodies or genetic mutations outcome. Therefore, the electroclinical presentation must
may support the definition of etiology, when conditions are be considered to interpret the case14.
available. According to the new 2017 ILAE classification, If the individual has a de novo mutation, their
there are 6 etiological groups: structural, genetic, infectious, offspring will have a 50% risk of inheriting the mutation.
metabolic, immune and unknown etiology. Epilepsy can However, this does not mean that their children will have
be classified into more than one etiological category, as the epilepsy, as its expression will still depend on the penetrance
same patient may have both structural and genetic etiology, of that mutation. A genetic etiology does not exclude an
such as patients with tuberous sclerosis. Structural etiology environmental contribution. For example, several patients
is a possible indication for epilepsy surgery, while genetic with epilepsy are more likely to have seizures under the
etiology is key for genetic counseling and consideration influence of sleep deprivation, stress and other factors14.
of new therapies such as mTOR (mammalian target of
rapamycin) inhibitors14. Infectious etiology
The most common etiology worldwide is epilepsy
Etiologies of epilepsies caused by an infection28. An epilepsy of infectious etiology
results from a known infection, in which seizures are a core
Structural etiology symptom of the disease. An infectious etiology is not related
The structural etiology refers to abnormalities to a patient who has acute symptomatic seizures in the
visible on neuroimaging, which along with clinical and acute phase of infections such as meningitis or encephalitis.
electrographic findings lead to the understanding that the Common examples in specific regions of the world
abnormality is the likely cause of the patient’s seizures14. include cysticercus infection such as neurocysticercosis,
Structural etiologies can be acquired, such as stroke, trauma, tuberculosis, HIV (Human Immunodeficiency Virus),
infection, hypoxic-ischemic encephalopathy; or genetic, cerebral malaria, subacute sclerosing panencephalitis,
such as many malformations of cortical development. A cerebral toxoplasmosis and congenital infections such
polymicrogyria may be secondary to mutations in genes as Zika virus and cytomegalovirus, which may have a
such as GPR5625. structural correlate. The infectious etiology can also refer
Despite there being a genetic basis for these to epilepsy that appears after an infection, as is the case of
malformations, the structural abnormality determines the viral encephalitis leading to seizures after the acute phase
existence of epilepsy. Whenever a structural etiology has of the infection14.
a well-defined genetic basis, such as tuberous sclerosis
complex, both etiological terms, structural and genetic, Metabolic etiology
can be used14. Epilepsy of metabolic etiology directly results from
a known or presumed metabolic disorder, in which seizures
Genetic etiology are the main symptom. Metabolic causes refer to metabolic
Genetic epilepsies result from a known genetic defects with clinical manifestations or biochemical changes
mutation or from one that can be inferred from genetic throughout the body, such as porphyria, uremia, amino-
etiology, in which seizures are the main symptom of the acidopathies or pyridoxine-dependent seizures. Most
disease. In the majority of cases, the underlying genes metabolic epilepsies are likely to have a genetic basis, but
are not yet known, and the genetic etiology may be based some can be acquired, such as cerebral folate deficiency.
solely on a family history suggestive of autosomal dominant The identification of specific metabolic causes of epilepsy
heredity. For example, in the syndrome of benign familial is extremely important due to the implications for treatment
neonatal epilepsy most families have mutations of one of and potential prevention of intellectual impairment14.

175
 Rev Med (São Paulo). 2020 March-April;99(2):170-81.

Immune etiology combination, which is not possible in less than ten years
Immune epilepsy results directly from an immune of therapy. Therefore, it is a relative concept and it can be
disorder in which seizures are the main symptom, when based on lack of seizure control after the use of several
there is evidence of autoimmune-mediated central nervous AEDs31.
system inflammation. The frequency of diagnosis is The definition of refractory epilepsy varies from
increasing because there is greater access to antibody study to study and there is no single classification. Some
testing. Examples include anti-NMDA (N-Methyl-D- studies consider it to be the occurrence of one seizure per
aspartate) receptor encephalitis and anti LGI1 (Anti month for a specified period of time, while others include
leucine-rich glioma inactivated 1) limbic encephalitis29. the ineffective drugs into the definition32.
This etiological subgroup deserves a specific category, More accepted definitions classify epilepsy as
mainly because of its implications for treatment with refractory when there is no appropriate control of seizures
targeted immunotherapies14. with the use of at least two or three antiepileptic drugs, at the
maximum tolerated dose, for a period of 18 to 24 months,
Unknown etiology or, if seizures are controlled but with an unacceptable side
effect33.
Unknown etiology means that the cause of the
The first indication of treatment for epilepsy in
epilepsy is not yet known. As the classification itself
general is the use of monotherapy. If there is no satisfactory
indicates, the nature of the causes is undetermined, and
response, two more attempts at monotherapy should be
there may be a probable genetic basis or structural/
made, followed by combination. If seizures still persist
metabolic disorder not yet identified21.
and new combinations fail, surgical intervention should
Many patients with epilepsy remain with an
be evaluated34. In cases where polytherapy is necessary
unknown cause. The determination of a specific diagnosis
and monotherapy has failed, the chance of effectiveness is
requires an extended evaluation; however, in many cases,
approximately 10%31.
this is not possible, as several countries have a shortage
In order to verify the response to treatment in
of resources.
relation to the time of drug therapy, it is necessary to
identify the frequency of the seizures. If the person has
New terminologies and applications
monthly seizures, it takes longer to verify the effectiveness
of the drug, usually several months. In cases of more
As a result of frequent epileptic activity, epileptic
frequent seizures, such as weekly seizures, one or two
encephalopathy may occur. This condition contributes to
months of are already enough to assess the therapeutic
severe cognitive and behavioral impairment and can be
response and, if there is an improvement, a longer treatment
applied to all epilepsies at any age, as deemed appropriate,
time is indicated31.
and not only to severe epilepsies beginning in infancy and
According to Benbadis and Tatum35, the emergence
in childhood, as previously defined 6.
of new antiepileptic drugs has resulted in a 50% seizure
The ILAE definition proposes the term “resolved
reduction and some of them have been used as adjunct
epilepsy”, previously defined as “cured”, to classify the
treatment for the control of refractory partial seizures.
remission of the disease. A period of at least ten years
These new drugs are: felbamate, gabapentin, lamotrigine,
without seizures and five years off antiseizure medication
topiramate, tiagabine, levetiracetam and zonisamide.
was established for the application of the term resolved
However, a study conducted by Yacubian36 demonstrated
epilepsy14.
that traditional drugs should be considered as the first
choice for the treatment of epilepsy in general.
Antiepileptic drug therapy
Regarding the new antiepileptic drugs, there is
Felbamate, which is indicated for focal and generalized
The appropriate choice of antiepileptic drugs
seizures. Gabapentin is another AED used as adjunct
(AEDs) is based on information collected about the type of
therapy for focal seizures in patients with intolerance to
seizure and/or epilepsy syndrome, age, tolerability, safety
multiple drugs with potential interactions. Lamotrigine has
and efficacy of the AED30. Complete seizure control is the
a broad spectrum of activity in various types of seizures,
main objective of the drug therapy; however, 20% to 30%
both as an adjunct treatment or as monotherapy; however,
of patients do not achieve complete control. These patients
one important side effect of this drug is rash, which can
can even present partial seizure control, but do not achieve
progress to Stevens-Johnson syndrome37.
complete remission. In these cases, when the possibility is
Topiramate has a broad spectrum of activity in
evaluated, surgery might be indicated23.
focal and generalized seizures. Nephrolithiasis is a rare
Refractory epilepsy can not be easily defined. In
side effect, and paresthesias and carbonic anhydrase
order to ascertain this diagnosis, it is necessary to use
inhibition reflexes are common side effects. Tiagabine has
all types of antiepileptic drugs in monotherapy and in
no significant side effects, and a limited spectrum of activity

176
Costa LLO, et al. Update on epilepsy: literature review.

in focal crises. Levitiracetam is indicated for focal seizures Essential Medications (RENAME), along with other drugs
and has good tolerability35. such as valproic acid and levetiracetam40.
Zonisamide is indicated as an adjunct therapy in
focal seizures; nephrolithiasis and weight loss are possible Alternative treatments: ketogenic diet, vagus nerve
side effects. Oxcarbamazepine is used as adjunct therapy stimulation and cannabidiol
and as monotherapy for focal crises, with hyponatremia
as its side effect37. The ketogenic diet is a lipid-rich low-calorie
The traditional drugs used to treat epilepsy are: diet, with reduction of glucose and restriction of fluid.
phenobarbital, phenytoin, carbamazepine, valproate and Its objective is to achieve a state of ketosis and it has an
benzodiazepines, which bind to plasma proteins and are antiepileptic effect, whose mechanism of action is not
metabolized by the liver23. completely understood. It is more effective in children
Phenobarbital is used in focal and generalized and adolescents because it enables the brain to revert to
seizures and status epilepticus. Side effects are sedation, the most primitive form of metabolism41.
ataxia and hyperactivity. Phenytoin is used in focal and This diet is indicated when drug therapy does
generalized seizures. Side effects are sedation and ataxia. not provide adequate seizure control in children with
Gingival hyperplasia and hirsustism may occur due to the multiple refractory seizures. It shows positive results in
proliferation of fibroblasts and lymphadenopathy36. There myoclonic, atonic, generalized tonic clonic, focal and
may be a deficiency in insulin secretion, particularly in absence seizures42.
diabetic and pre-diabetic patients38. A skin rash might The main complications of this diet are
be an idiosyncratic reaction of both phenobarbital and hypoglycemia, excess ketosis, diarrhea, reduced appetite,
phenytoin36. thirst, drowsiness, dehydration, metabolic acidosis,
Carbamazepine is effective in treating focal and hyperuricemia and hyperlipidemia. Exams should be
generalized seizures. There are reports that it can trigger monitored, and any alteration should be observed31.
or exacerbate absence seizures. Side effects are food Vagus nerve stimulation is a minimally invasive
intolerance, sedation and ataxia. Idiosyncratic reactions method that is another alternative treatment for refractory
include leukopenia, aplastic anemia, rash and Stevens- epilepsy. It is a pulse generator that is implanted under
Johnson syndrome. Oxcarbamazepine has the same the skin, below the clavicle, in the same position as a
principle as carbamazepine, but the difference is in positions pacemaker43.
10 and 11 of the molecule, where oxcarbamazepine has a Its mechanism of action is still not known. However,
ketone group, which reduces side effects. Its half-life is it is believed that it activates projections in the nucleus
longer, so it is administered two times a day36. of the solitary tract to the limbic forebrain23, through the
Valproic acid provides good seizure control in release of noradrenaline by the locus coeruleus in the limbic
generalized tonic-clonic, absence, myoclonic and primary cortex and of serotonin by the dorsal raphe nuclei in the
seizures, with a lesser effect on focal seizures. Side effects telencephalon and diencephalon44.
are tremor, weight gain, dyspepsia, nausea, vomiting, The pulse generator is programmed through the
anorexia, alopecia, peripheral edema, encephalopathy, computer and stimulation usually begins two weeks after
teratogenesis, agranulocytosis, aplastic anemia, allergic the surgical implant. Most patients experience reduced
dermatitis, Stevens-Johnson syndrome, hepatotoxicity and seizure frequency, improved cognition, better quality
platelet changes39. of life and reduced depression, but there is no report of
Benzodiazepines act at the receptor sites in the complete seizure control. The most common side effects
central nervous system, specifically at the receptor sites are hoarseness, coughing and paresthesia of the pharynx
of the most common inhibitory neurotransmitter, gamma- due to the intensity of the stimuli43.
aminobutyric acid (GABA). They also affect channel Another treatment used for epilepsy in selected
opening frequency. Clonazepam and diazepam are used cases is cannabidiol. Cannabis sativa is a plant that contains
in emergency situations and clobazam and nitrazepam are approximately 100 pharmacologically active components.
used for chronic treatment of epilepsy23. One of these components, the cannabidiol (CBD), was
The Brazilian Ministry of Health has a Clinical identified in 196345. It has no psychoactive effect, a low
Protocol and Therapeutic Guideline (PCDT) with toxicity and high tolerability in humans and animals46.
guidelines on diagnosis, treatment and monitoring of Cannabidiol (CBD) and Tetrahydrocannabinol
epilepsy. The PCDT recommends the following drugs (THC) are the most common components in cannabis
for the treatment of epilepsy: carbamazepine, clobazam, sativa. They have opposing effects: while THC is the main
ethosuximide, phenytoin, phenobarbital, primidone, psychoactive component, due to its role as a partial agonist
gabapentin, topiramate, lamotrigine and vigabatrin. These of cannabinoid receptors (CB1), CBD acts by reducing the
medications are on the list of drugs available in the Unified effects of the activation of this receptor47.
Health System (SUS) and in the 2020 National List of Cannabinoids act by binding to receptors; one of

177
 Rev Med (São Paulo). 2020 March-April;99(2):170-81.

them, the CB1, is located in the central nervous system45 imaging has a better resolution, which helps to visualize
and is present in both inhibitory gabaergic neurons and structural changes. New techniques, such as multiplanar
excitatory glutamatergic neurons47. Cannabidiol acts on this reconstruction, can help identifying lesions when
receptor by inhibiting synaptic transmission by blocking conventional methods cannot. This method has a 94%
voltage-dependent calcium-activated (Ca2+) potassium (K+) sensitivity for detecting injuries55.
channels. The mechanism of action of cannabidiol has not F o r m a n y p a t i e n t s w i t h e p i l e p s y, t h e
been fully elucidated; however, it is believed that this is electroencephalogram or the resonance cannot identify
how cannabidiol can reduce seizures45. epileptogenic focus and some have to undergo interictal
Its antiepileptic effect has been proven, as clinical and ictal scalp EEG, an invasive method to evaluate
studies show the beneficial effects of CBD against seizures, surgical intervention. There are less invasive methods
such as a significant improvement of seizures in refractory such as PET (positron emission tomography) and SPECT
epilepsis, total or partial remission in most of the patients (single photon emission computed tomography), which are
analyzed, and even increased alertness in many children48. functional neuroimaging exams that identify alterations of
A double-blind, placebo-controlled trial conducted blood flow with the use of radiopharmaceuticals and which
by Devinsk et al. in 2017, evaluated 120 children and have been proven to be useful in the identification of the
young adults with the Dravet syndrome and drug-resistant epileptic area55.
seizures. One group received CBD 20 mg per kg per
day and the other group received placebo, in addition to Care for people with epilepsy
standard treatment. The use of CBD resulted in a significant
reduction in seizure frequency and a higher rate of adverse Knowledge about epilepsy and recognition of
events compared to placebo49. crises are essential for professionals who care for epileptic
Although cannabidiol shows excellent results, there patients. In addition, it is necessary to have skill and
is still no clarification on safety of long-term administration, determination in situations in order to avoid neurological
pharmacokinetic properties, mechanism of action and problems and take action to avoid greater risks such as falls,
pharmacological interaction with other cannabinoids50. aspiration of pulmonary secretions and injuries. Actions
Therefore, it should be used with caution in patients in the such as administration of anticonvulsants, maintenance
stage of cognitive development, particularly children and of an open airway, lateral positioning of the head,
adolescents51. administration of oxygen if necessary are management and
The Federal Council of Medicine (CFM) regulated damage prevention measures56.
the use of cannabidiol in Brazil in resolution No. 2,113/14. Patient and family members must be informed
It is indicated in cases of drug-resistant epileptic syndromes. about the disease, the importance of adhering to treatment
The medications used by the patient are kept, in association and complying with regular medication schedules, the
with cannabidiol52. In Brazil, the medical use of drugs based adverse drug effects and the risks of untreated epilepsy.
on CBD and THC was authorized by the National Health Professionals should verify if the treatment is being
Surveillance Agency - ANVISA53. properly carried out and provide guidance regarding care
Cannabidiol has a demonstrated anticonvulsant during and after seizures57.
effect, so it is being used therapeutically. However, it The seizure diary is an important instrument to assist
requires further research to elucidate its properties and medical treatment. It contains information on duration,
safety. frequency, time and characterization of the seizures, body
parts involved, triggering factors, state of consciousness,
Diagnostic exams pharmacological actions and side effects. Family members
who live with the patient should be instructed to make these
According to Smith54, the electroencephalogram notes, as the seizure diary allows a qualified and unique
has a fundamental role in the identification of seizures and treatment that may lead to improvement in the patient’s
patterns of syndromes; it also contributes to the selection quality of life57.
of appropriate drug therapy and assists in the prognosis.
Ambulatory and video electroencephalogram are CONCLUSION
indicated for patients who do not have a clearly defined
diagnosis and for differentiation between nocturnal epilepsy Epilepsy has peculiarities that must be well defined
and parasomnias, diagnosis of psychogenic non-epileptic and understood, especially when it is difficult to control.
seizures, characterization of seizure type, quantification The knowledge about the type of crisis, the etiology, the
of seizure frequency and evaluation of candidates for predisposing factors and the pharmacological actions for
surgery54. each type of crisis is essential for an adequate management
Computed tomography is also used for diagnosis; of epilepsy.
however, for a better investigation, magnetic resonance The constant observation of the patient’s evolution,

178
Costa LLO, et al. Update on epilepsy: literature review.

recording details of all aspects of the epilepsy and checking interventions that, in many situations, result in satisfactory
the particularities of each case, enables appropriate results, in a holistic view of the patient’s health.

Contribution of the authors of the study: Costa LLO - Survey of bibliographic data, selection of data sources, writing and review; Brandão
EC - Writing of methods and review; Marinho Segundo LMB - Advisor and review of the text.

REFERENCES CE, et al. A practical clinical definition of epilepsy. International

League Against Epilepsy. Epilepsia. 2014;55(4):475-82. doi:
10.1111/epi.12550.
1. Fernandes MJS. Epilepsia do lobo temporal: mecanismos e
perspectivas. Estud Av. 2013;27(77):85-96. doi: 10.1590/S0103- 14. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French
40142013000100007. J, Guilhoto L, et al. Classificação das epilepsias da ILAE:
Relatório da Comissão de Classificação e Terminologia da
2. Rektor I, Schachter SC, Arzy S, Baloyannis SJ, Bazil C, Brázdil ILAE. Epilepsia. 2017;58(4):512-21. doi: 10.111/epi.13709.
M, et al. Epilepsy, behavior, and art (Epilepsy, Brain, and
Mind, part 1). Epilepsy Behav. 2013;28:261-82. doi: 10.1016/j. 15. Mourente-Diaz S, Montenegro MA, Lowe JP, et al. Unusual
yebeh.2013.03.011. focal ictal pattern in children with eyelid myoclonia and
absences. Pediatr Neurol. 2007;37:292-5. doi: 10.1016/j.
3. Yacubian EMT. Epilepsias em: Nitrine R, Bacheschi LA. A pediatrneurol.2007.05.014.
neurologia que todo médico deve saber. 2a ed. São Paulo:
Atheneu; 2008. p.235-56. 16. Kelley SA, Kossoff EH. Doose syndrome (myoclonic-astatic
epilepsy): 40 years of progress. Dev Med Child Neurol. 2010;
4. Gallucci Neto J, Marchetti RL. Aspectos epidemiológicos 52:988–993. doi:10.1111/j.1469-8749.2010.03744.x.
e relevância dos transtornos mentais associados à epilepsia.
Rev Bras Psiquiatr. 2005; 27:323-8. doi: 10.1590/S1516- 17. Wolf P, Yacubian EM, Avanzini G, et al. Juvenile myoclonic
44462005000400013. epilepsy: a system disorder of the brain. Epilepsy Res. 2015;
114:2-12. doi: 10.1016/j.eplepsyres.2015.04.008.
5. Scharfman HE. The neurobiology of epilepsy. Curr Neurol
Neurosci Rep. 2007;7(4):348-54. doi: 10.1007/s11910-007- 18. Striano S, Capovilla G, Sofia V, et al. Eyelid myoclonia with
0053-z. absences (Jeavons syndrome): a well-defined idiopathic
generalized epilepsy syndrome or a spectrum of photosensitive
6. Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, conditions? Epilepsia. 2009;50(5):15-9. doi: 10.1111/j.1528-
Jansen FE, et al. Operational classification of seizure types 1167.2009.02114.x.
by the International League Against Epilepsy: Position Paper
of the ILAE Commission for Classification and Terminology. 19. Zuberi SM, Symonds JD. Atualização sobre o diagnóstico
Epilepsia. 2017;58(4):522-530. doi:10.1111/epi.13670. e tratamento de epilepsia na infância. J Pediatr. 2015;91(6
Suppl.1). doi: 10.1016/j.jped.2015.07.003.
7. Shorvon SD. The etiologic classification of epilepsy. Epilepsia.
2011;52(6):1052-7. doi:10.1111/j.1528-1167.2011.03041.x. 20. Blume WT, Luders HO, Mizrahi E, Tassinari C, Van Emd
Boas W, Engel J. Glossary of Descriptive Terminology
8. Kwan P, Brodie MJ. Seizure. Refractory epilepsy: a for Ictal Semiology: Report of the ILAE Task Force on
progressive, intractable but preventable condition? Seizure. Classification and Terminology. Epilepsia. 2001;42(9):1212-
2002;11(2):77-84. doi: 10.1053/seiz.2002.0593. 8. doi: 10.1046/j.1528-1157.2001.22001.x.
9. Hermann BP, Seidenberg M, Dow C, Jones J, Rutecki P, 21. Yacubian EMT. Proposta de Classificação das Crises e
Bhattacharya A, et al. Cognitive prognosis in chronic temporal Síndromes Epilépticas. Correlação Videoeletrencefalográfica.
lobe epilepsy. Ann Neurol. 2006; 60:80-7. doi: 10.1002/ Rev Neurociências. 2002;10(2):49-65.
ana.20872.
22. Aminof M.J. Nervous sistems disorders. In: McPhee SJ,
10. Jacoby A, Baker GA. Quality of life trajectories in epilepsy: Papadakis MA. Current medical diagnosis and treatment.
a review of the literature. Epilepsy Behav. 2008;12:557-71. 49th ed. New York: McGraw Hill Lange; 2009. p.878-89.
doi: 10.1016/j.yebeh.2007.11.013.
23. Yacubian EMT, Caicedo GC, Pohl LR. Epilepsias: tratamento
11. Ren WHP. Anesthetic management of epileptic pediatric medicamentoso: medicina. São Paulo: Leitura Médica Ltda;
patients. Int Anesthesiol Clin. 2009;47:101-16. doi: 10.1097/ 2014. p.27-5.
AIA.0b013e3181ac2539.
24. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH,
12. Liberalesso PBN. Epilepsias na infância: diagnóstico e van Emde Boas W, et al. Revised terminology and concepts
tratamento. Rev Pediatr Mod. 2007;43(6):274-82. for organization of seizures and epilepsies: report of the
13. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger ILAE Commission on Classification and Terminology, 2005-

179
 Rev Med (São Paulo). 2020 March-April;99(2):170-81.

2009. Epilepsia. 2010;51(4):676-85. doi: 10.1111/j.1528- Philaddephia: Lippincott Williams Wilkins; 2009. p.623-43.
1167.2010.02522.x.
40. Brasil. Ministério da Saúde. Secretaria de Ciência, Tecnologia,
25. Guerrini R, Dobyns WB. Malformations of cortical Inovação e Insumos Estratégicos em Saúde. Departamento
development: clinical features and genetic causes. Lancet de Assistência Farmacêutica e Insumos Estratégicos. Relação
Neurol. 2014;13:710-26. doi: 10.1016/S1474-4422(14)70040- Nacional de Medicamentos Essenciais: Rename 2020 [citado
7. 28 nov. 2019]. Disponível em: http://portalms.saude.gov.br/
assistencia-farmaceutica/medicamentos-rename.
26. Tinuper P, Bisulli F, Cross JH, et al. Definition and diagnostic
criteria of sleep-related hypermotor epilepsy. Neurology. 41. Pereira AM, Kaemmererb C, Palmini A, Nunes MA.
2016;86:1834-42. doi: 10.1212/WNL.0000000000002666. Avaliação da arquitetura do sono em crianças com epilepsia
refratária. J Epilepsy Clin Neurophysiol. 2011;17(1):10-16.
27. Wolf P. Much ado about nothing? Epilepsia. 2010;51:717–8.
doi: 10.1590/S1676-26492011000100004.
28. Vezzani A, Fujinami RS, White HS, et al. Infections,
42. Ramos AMF. Eficácia da dieta cetogênica no tratamento
inflammation and epilepsy. Acta Neuropathol. 2016;131:211-
da epilepsia refratária em crianças e em adolescentes. Rev
34. doi: 10.1007/s00401-015-1481-5.
Neurociências. 2001;9(3):127-31.
29. Lancaster E, Dalmau J. Neuronal autoantigens–pathogenesis,
43. Meneses MS, Rocha SFB, Simão C, Santos HNHL, Pereira
associated disorders and antibody testing. Nat Rev Neurol.
C, Kowacs PA. Estimulação no nervo vago pode ser uma
2012;8:380-90. doi: 10.1038/nrneurol.2012.99.
excelente opção no tratamento de epilepsias refratárias. Arq
30. French JA, Kanner AM, Bautista J, Abou-Khalil B, Neuropsiquiatr. 2013;71(1):25-30. doi: 10.1590/S0004-
Browne T, Harden CL, et al. Efficacy and tolerability 282X2013000100006.
of the new antipiletic drugs II: treatment of refractory
44. Krahl SE, Clark KB. Vagus nerve stimulation for epilepsy: a
epilepsy. Neurology. 2004;62:261-1273. doi: 10.1212/01.
review of central mechanisms. Surg Neurol Int. 2012;3(4):255-
wnl.0000123695.22623.32.
9. doi: 10.4103/2152-7806.103015.
31. Garzon E. Epilepsia refratária: conceito e contribuição
45. Hofmann ME, Frazier CJ. Marijuana, endocannabinoides, and
das novas drogas antiepiléticas e de outras modalidades
epilepsy: potential and challenges for improved therapeutic
terapêuticas. Rev Neurociências. 2002;0(2):66-82.
intervention. Exp Neurol. 2013;244:43-50. doi: 10.1016/j.
32. French JA. Refractory epilepsy: one size does not fit all. expneurol.2011.11.047.
Epilepsy Curr. 2006;6(6):177-80. doi:10.1111/j.1535-
46. Jones NA, Glyn SE, Akiyama S. Cannabidiol exerts anti-
7511.2006.00137.x.
convulsant effects in animal models of temporal lobe and
33. Campfield P, Campfield C. Pediatric epilepsy: an overview. partial seizures. Seizure. 2012;21:344-52. doi: 10.1016/j.
In: Swaiman A, Ashal S, Ferrreiro D. Pediatric neurology, seizure.2012.03.001.
principles & pratice. Philadelphia: Mosby Elsevier; 2012.
47. Lutz B. On-demand activation of the endocannabinoid
34. Betting LE, Kobayashi E, Montenegro MA, Min LL, Cendes system in the control of neural excitability and epileptiform
F, Guerreiro MM et al. Tratamento de epilepsia: consenso dos seizures. Biochem Farmacol. 2004;68:1691-8. doi: 10.1016/j.
especialistas brasileiros. Arq Neuropsiquiatr. 2003;61(4):1045- bcp.2004.07.007.
70. doi: 10.1590/S0004-282X2003000600032.
48. Porter BE, Jacobson C. Report of a parent survey of
35. Benbadis SR, Tatum WO. Advances in the treatment of cannabidiol-enriched cannabis use in pediatric treatment-
epilepsy. Am Fam Physician. 2001;64(1):91-98. Available resistant epilepsy. Epilepsy Behav. 2013;29(3)574-7. doi:
from: https://www.aafp.org/afp/2001/0701/p91.html. 10.1016/j.yebeh.2013.08.037.
36. Yacubian EMT. Tratamento da epilepsia na infância. 49. Devinsky O, Cross JH, FRCPCH, Laux L, Marsh E,Miller I et
J Pediatria. 2002;1(78):19-27. doi: 10.1590/S0021- al. Trial of Cannabidiol for Drug-Resistent Seizures in the Dravet
75572002000700005. Syndrome. N Engl J Med. 2017;376(21):2011-20. doi: 10.1056/
37. Maranhão MVM, Gomes EA, Carvalho PE. Epliepsia e NEJMoa1611618.
anestesia. Rev Bras Anestesiol. 2011;61(2):232-54. doi: 50. Brucki SMD, Frota NA, Schestatsky P, Souza AH, Carvalho
10.1590/S0034-70942011000200013. VN, Manreza MLG, Jurno ME. Canabinoides e seu uso em
38. Shimazaki JC. Drogas antiepiléticas tradicionais. In: Cukiert neurologia. Arq Neuropsiquiatr. 2015;73(4):371-74. doi:
A. Tratamento clínico e cirúrgico das epilepsias de difícil 10.1590/0004-282X20150041.
controle. São Paulo: Lemos Editorial; 2002. p.41-47. 51. Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French
39. Stoelting RK. Antiepileptic drugs. In: Stoelting RK. J, Hill C, et al. Cannabidiol: Pharmacology and potential
Pharmacology and phisiology in anesthesic pratice. 4th ed. therapeutic role in epilepsy and other neuropsychiatric

180
Costa LLO, et al. Update on epilepsy: literature review.

disorders. Epilepsia. 2014;55(6):791-802. doi: 10.1111/ 55. Bilevicius E, Etchebehere ECSC, Camargo EE, Yasuda CL,
epi.12631. Cendes F. Avaliação pré-cirúrgica de epilepsia neocortical
de lobo temporal com utilização de FDG - F spect: relato de
52. Conselho Federal de Medicina (CFM). Resolução no
caso. J Epilepsy Clin Neurophysiol. 2006;12(3):169-73. doi:
2.113/14. Diário Oficial da União, 15 dez. 2014. Seção I.
10.1590/S1676-26492006000500010.
p.183.
56. Lima CC, Poles K, Marques SM. Cuidados de enfermagem a
53. Brasil. Agência Nacional de Vigilância Sanitária. Portaria
crianças em crises convulsivas. Pediatria. 2011;33(3):142-9.
SVS/MS nº 344/9. Dispõe sobre a atualização do Anexo
I (Listas de Substâncias Entorpecentes, Psicotrópicas, 57. Jesus MBP, Nogueira VO. Diagnósticos de enfermagem de
Precursoras e Outras sob Controle Especial). Diário Oficial pacientes pediátricos com epilepsia: um estudo prospectivo.
da União, 5 dez. 2016. Seção I, p.33. Conscientiae Saúde. 2008;7(1):101-7. doi: 10.5585/conssaude.
v7i1.748.
54. Smith SJM. EEG in the diagnosis, classification and
management of pacients with epilepsy. J Neurol Neurosurg Received: April 25, 2019
Psichiatry. 2005;76(2):2-7. doi: 10.1136/jnnp.2005.069245. Accepted: January 29, 2020

181