Part I
The Clinical Practice Guidelines
for Epilepsy 2018

Chapter 1
Diagnosis, Classification and Differential
Diagnosis of Epilepsies (Including REM Sleep
Behavior Disorder)
CQ 1-1

What is epilepsy?
Summary
Epilepsy is a disease characterized by an enduring predisposition to generate epileptic seizures. In other words,
epilepsy is a chronic brain disease, in which abnormal hyperexcitable neurons in the brain cause recurrence of seizure
symptoms. Seizures occur suddenly, manifesting physical symptoms different from the normal state, alteredconsciousness, and motor and sensory changes. The possibility of epilepsy is adequately high if accompanied by
seizures.

Comment
Cerebral neurons generate regular rhythm electrically, while maintaining synchronous neuronal activity in the brain.
Epilepsy is caused by a sudden disturbance of this activity accompanied by abnormal, disorderly discharges of the electricalactivities of neurons in the brain (excessive excitation or synchronization). This may occur in an afebrile state, and the seizure
symptoms are diverse depending on the region of the brain that is involved in the abnormal electrical activity1). These
symptoms include not only “convulsions and spasms” but also various symptoms such as “feeling black out”, “jerking of thebody”, “moving around with loss of consciousness” (see CQ1-4 on page 10, and CQ1-5 on page 11). In addition, epilepsy ischaracterized by recurrence. Electroencephalography (EEG) has a central role in various examinations and is necessary toestablish the diagnosis (see CQ1-6 on page 13).
Traditionally, epilepsy was defined as “two unprovoked seizures occurring at intervals of longer than 24 hours”. In 2014,a task force of the International League Against Epilepsy Organization (ILAE) recognized that epilepsy may be present inspecial circumstances that do not meet the criteria of “two unprovoked seizures”. In order to address this issue, the task force
proposed to consider epilepsy as a disease of the brain defined by any of the following criteria 2): (1) at least two unprovoked(or reflex) seizures occurring at intervals of longer than 24 hours; (2) one unprovoked (or reflex) seizure and a probability offurther seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next
10 years (see Note below); and (3) diagnosis of an epilepsy syndrome.
The term “unprovoked seizure” is a term that describes spontaneous seizure as a chronic disease without a definitive
trigger. In contrast, “provoked seizure” is also known as acute symptomatic seizure or situation-related seizure, which occurs
secondary to acute brain disorders such as encephalitis, trauma, cerebrovascular disorders, and metabolic disorders 3).
Note: Number (2) in the second paragraph signifies that if there is one unprovoked seizure and the risk of recurrence canbe proven to be over 60%, then patient care should be initiated assuming a diagnosis of epilepsy. Some specific examples
include patients with a single seizure occurring at least one month after onset of stroke, and children with a single seizure
simultaneous with a structural or indirect symptomatic etiology for the symptom and an epileptiform EEG. Another example
is patients in whom a specific epilepsy syndrome associated with persistent threshold change can be detected after a single
seizure. Even when the first seizure manifests as status epilepticus, this by itself does not imply epilepsy 2).

2

Part IThe Clinical Practice Guidelines for Epilepsy 2018

▪ References
1) Iinuma K, Fujiwara T, Ikeda A, et al. Japan Epilepsy Society, Task Force on Guideline Committee. Guideline for Diagnosis of Epilepsy. Tenkan
Kenkyu. 2008; 26(1): 110-113 (in Japanese).
2) Fisher RS, Accvedo C, Arzimanoglou A, et al. ILAE Official Report. A practical clinical definition of epilepsy. Epilepsia. 2014; 55(4): 475-482.
3) Beghi E, Carpio A, Forsgren L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia. 2010; 51(4): 671-675.

▪ Search formula and secondary reference sources
PubMed search: September 12, 2008
epilepsy [Mesh] and (define* OR definition*) = 2,382
No references that could serve as evidence were found in Ichushi Web.
PubMed search: June 28, 2015((((((((epilepsy/classification [majr] OR epilepsy/diagnosis [majr])) AND ((define* OR definite*)))) AND (Humans [Mesh] AND (English [LA] OR
Japanese [LA]))) AND (“2008” [Date-Publication]: “2015” [Date-Publication]))) AND ((“ILAE”) OR (“NICE” OR “National Institute for Healthand Care Excellence”)) = 17
Ichushi search: June 25, 2015(((Differential diagnosis/TH) and (((REM sleep behavior disorder/TH or REM sleep behavior abnormality/AL) or (epilepsy/MTH)) and (Japan
Epilepsy Society/AL)))) and (DT = 2008:2015 and PT = excluding proceedings and CK = human) = 6

Chapter 1  

3

CQ 1-2

What are the key clinical features to be included in history
taking for epilepsy diagnosis?
Summary
Accumulation of detailed information (medical history) and a witness of the actual seizure are most useful for the
diagnosis of epilepsy. The chief complaint in most cases is a convulsive seizure (non-convulsive seizure in some cases).
However, usually it is necessary to confirm the history of the seizure at least twice in order to diagnose epilepsy.

Comment
Detailed history taking of clinical features 1 to 3 described below is important for making a diagnosis1, 2).

1. It is important to obtain seizure information from the patient and a witness of the seizure.
a.	 Frequency of seizureb.	 Situation and trigger of the seizure (such as photosensitivity)c.	 Symptoms before and during seizure (physical symptoms, psychological symptoms, and consciousness impairment)d.	 Duration of symptomse.	 Symptoms after the seizuref.	 Presence or absence of injury, tongue bite and urinary incontinenceg.	 Headache and muscle pain after seizureh.	 A ge of the first seizure for a patient with multiple seizuresi.	 Change and evolution of seizure and type of seizurej.	 The last seizurek.	 Relation between seizure and wake-sleep states

2. It is important to include the following clinical features in history taking from a witness of seizure.
a.	 Frequency of seizureb.	 Detailed situations observed before and during seizure (patient’s response, arm and leg movements, open or closed
eyes, eyeball displacement, making sound, facial pallor, respiration and pulse)c.	 Details of movements and behaviors after seizured.	 Video recorded by family members

3. When recording the medical history in the clinical record, it is important to include the following
demographic characteristics.
a.	 A ge (many epilepsies are age-dependent)b.	 Sexc.	 Past history (including perinatal abnormalities, febrile convulsions, head trauma, and mental illness)d.	 Comorbid conditions (see Table 1)e.	 History of alcohol consumption, regular medications, and history of narcotic usef.	 Family historyg.	 Social history

4

Part IThe Clinical Practice Guidelines for Epilepsy 2018

▪ References
1) Scottish Intercollegiate Guidelines Network. Diagnosis and management of epilepsy in adults. A national clinical guideline, 2003, p.3-7.
2) Stokes T, Shaw EL, Juarez-Garcia A, et al. Clinical Guidelines and Evidence Review for the Epilepsies: diagnosis and management in adults andchildren in primary and secondary care. London: Royal College of General Practitioners, 2004, p. 49-50, 85-95.

▪ Search formula and secondary reference sources
PubMed search: October 30, 2008((epileptic seizures or epilepsy) and diagnosis and (interview or (history taking)) and (“sensitivity and specificity” [mh] OR sensitivity [tiab] OR
specificity [tiab] OR likelihood ratio* OR practice guideline [pt] OR likelihood functions [mh] or meta-analysis [mh] OR meta-analysis [pt] ORmetaanaly* [tiab] OR “meta analysis” OR multicenter study [pt] OR evaluation studies [pt] OR validation studies [pt] OR systematic review* OR
systematic [sb] = 58
No references that could serve as evidence were found in Ichushi Web.
PubMed search: June 28, 2015((((((((epilepsy [majr]) AND medical history taking [mesh])) AND (“2008” [Date-Publication]: “2015” [Date-Publication])) AND (English[Language] OR Japanese [Language]))) AND Humans [Filter])) AND (“ILAE” OR “NICE”) = 0
Ichushi search: June 25, 2015(((((epilepsy/MTH)) and (SH = diagnosis)) and (history taking/MTH))) and (DT = 2008:2015 and PT = excluding proceedings) = 0

Table 1. Main comorbid conditions of epilepsy.
1. Birth asphyxia
2. Brain malformation
3. Genetic abnormality
4. Chromosomal abnormality
5. Developmental disorder
6. Metabolic abnormality
7. Hypoxia

8. Central nervous system infection
9. Autoimmune encephalitis
10. Cerebral hemorrhage
11. Cerebral infarction
12. Brain tumor
13. Brain trauma
14. Dementia

Chapter 1  

5

CQ 1-3

How are epileptic seizure types, epilepsies, epilepsy syndromes,
and related seizure disorders classified?
Summary
Classification of epileptic seizures is indispensable for subsequent patient care, examinations, and choice ofantiepileptic drugs. The ILAE classifications are widely used. Diagnosis of epilepsy for patients has importantsignificance on physical, mental, social and economic status. Therefore, it is recommended that specialists conduct
definitive clinical diagnosis of epilepsy.

Comment
Currently, the following ILAE classifications are widely used in Japan: the classification of epileptic seizures of 1981 1) andthe classification of epilepsies, epileptic syndromes and related seizure disorders of 1989 2). However, the ILAE task force
proposed a new disease classification in 2010 3). Tables 1 and 2 show the corresponding classification categories in the new
and old classifications of 1981, 1989 and 2010 4). This guideline follows the classification of seizure types of 1981, in which
epileptic seizures are divided into partial and generalized seizures. “Partial” is used to indicate “focal” or “localizationrelated”.
The feature of the 1981 classification of seizure types is based on an accurate correspondence between seizure symptoms
and EEG findings (left column of Table 1), and the scheme is based on “epileptic discharge” on EEG, which is the information
with the highest sensitivity and specificity. On the other hand, the feature of the 1989 classification of epilepsies and epilepsy
syndromes is based on a 2 × 2 classification table (left column of Table 2). With this classification, idiopathic epilepsies andsyndromes are not necessary only generalized epilepsies but also include some partial epilepsies. Conversely, within
symptomatic epilepsies and syndromes, partial epilepsies and generalized epilepsies are both clearly classified. Furthermore,among these four categories, apart from symptomatic partial epilepsies, all the others have in principle age-dependent onset
and reflect the element of onset age at the same time.
1. Idiopathic partial epilepsies are benign, (1) with childhood onset, (2) manifest localization-related seizure symptoms andlocalized EEG findings, (3) show no abnormal neuroimaging findings, and (4) remit by adolescence. This category
includes benign epilepsy with centrotemporal sharp waves and Panayiotopoulos type with focus in the occipital region.
2. Symptoms suggestive of symptomatic partial epilepsies include: (1) a history of disease that may constitute the etiology,(2) aura, (3) local motor or sensory signs at onset or during seizure, and (4) automatism. However, even with absence
seizures, automatism may sometimes occur.
3. Idiopathic generalized epilepsies rarely have onset older than at 25 years of age and show no other neurological symptoms.
The symptoms suggesting this category include: (1) childhood onset (before adolescence), (2) induced by sleep deprivation
and alcohol, (3) tonic-clonic seizure or myoclonic seizure immediately after waking, (4) seizure type is absence, with noother neurologic symptoms (5) spontaneous photoreaction on EEG, including generalized 3-Hz spike-and-slow-wave
complexes or multiple spike-and-slow-wave complexes.
4. Symptoms suggestive of symptomatic generalized epilepsies include: (1) very early onset (neonatal period, infancy: under
1 year of age), (2) frequent seizures, (3) mental retardation and neurological symptoms from before onset, (4) progression
and regression of neurological symptoms, (5) diffuse EEG abnormalities, and (6) organic morphological abnormalities inthe brain.

6

Part IThe Clinical Practice Guidelines for Epilepsy 2018

The basic concepts for the 2010 classifications are as follows.
1. Modes of seizure manifestation and classification of seizures
The term partial seizure is eliminated, and is replaced by “focal seizures” (with or without impairment of consciousness)(right column of Table 1). “Generalized” and “focal” are redefined. Generalized seizures are seizures that occur within the
network of bilateral cerebral hemispheres, and this network is rapidly involved in seizure. Focal seizures are seizures that
occur within the network limited to unilateral cerebral hemisphere and is either discretely localized or more widelydistributed within unilateral hemisphere.
2. Classification of underlying causes
Instead of the traditional terms “idiopathic”, “symptomatic” and “cryptogenic”, the 2010 classification recommends
modified concepts using the new terms “genetic”, “structural-metabolic” and “unknown”.
This chapter is based on the classifications reported up to the time of this writing (2016), and the classifications publishedthereafter are not addressed.

▪ References
1) Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminologyof the International League Against Epilepsy. Epilepsia. 1981; 22(4): 489-501.
2) Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League
Against Epilepsy. Epilepsia.1989; 30(4): 389-399.
3) Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts of organization of seizures and epilepsies: Report of the ILAE Commission
on Classification and Terminology, 2005-2009. Epilepsia. 2010; 51(4): 676-685.
4) Tobimatsu S. Chapter 1. Epidemiology of Epilepsy. 2. Classification (comparison of 1981, 1989 and 2010). In: Guidebook for Epileptologists, Japan
Epilepsy Society (Ed.) Shindan To Chiryousha, Tokyo. 2014, p. 5-10 (in Japanese).

▪ Search formula and secondary reference sources
PubMed search: October 17, 2008((epileptic seizures) or epilepsy) and diagnosis and (classification or categorization) and (“sensitivity and specificity” [mh] OR sensitivity [tiab] OR
specificity [tiab] OR likelihood ratio* OR practice guideline [pt] OR likelihood functions [mh] or meta-analysis [mh] OR meta-analysis [pt] ORmetaanaly* [tiab] OR “meta analysis” OR multicenter study [pt] OR evaluation studies [pt] OR validation studies [pt] OR systematic review* OR
systematic [sb] = 273
No references that could serve as evidence were found in Ichushi Web.
PubMed search: June 28, 2015(((((((epilepsy/classification [majr]) AND classification [ti])) AND(“2008” [Date-Publication]: “2015” [Date-Publication])) AND (English[Language] OR Japanese [Language])) AND Humans [Filter])) AND (“ILAE” OR “NICE”) = 22
Ichushi search: June 25, 2015(((epilepsy/MTH) and (classification/TI))) and (DT = 2008:2015 and PT = excluding proceedings) = 0

Chapter 1  

7

Table 1. International classifications of epileptic seizure types: corresponding categories for the 1981classification and the 2010 revised classification.
1981 classification of seizure type a2010 revised classification of seizure type b

Partial (focal, local) seizures

Focal seizures

A. Simple partial seizures (consciousness not impaired)
1. With motor signs
2. With somatosensory or special sensory symptoms
3. With autonomic symptoms or signs
4. With psychiatric symptoms (most experienced as “complex
partial seizures”

A. Without impairment of consciousness With observable motor or autonomic components. Thisroughly corresponds to the concept of “simple partial seizure.
“Focal motor” and “autonomic” are terms that may adequately
convey this concept depending on the seizure manifestations).
 Involving subjective sensory or psychic phenomena only. This
corresponds to the concept of an aura, a term endorsed in the2001 Glossary.

B. Complex partial seizures
1. Simple partial onset followed by impairment of consciousness   a. With simple partial at onset   b. With automatism at onset   c. With impairment of consciousness at onset

B. With impairment of consciousness This roughly corresponds to the concept of complex partial
seizure. “Dyscognitive” is a term that has been proposed forthis concept.

C. Partial seizures evolving to secondarily generalized seizures
1. Simple partial seizures (A) evolving to generalized seizures
2. Complex partial seizures (B) evolving to generalized seizures
3. Simple partial seizures evolving to complex partial seizures
evolving to generalized seizures

Evolving to a bilateral, convulsive seizure (involving tonic, clonic,
or tonic-clonic components). This expression replaces the term“secondarily generalized seizure.

Generalized seizures

Generalized seizures

A. 1. Absence seizures   a. Impairment of consciousness only   b. With mild clonic components   c. With atonic components   d. With tonic components   e. With automatisms   f. With autonomic component (b-f may be alone or in
combination)
2. Atypical absence seizure   a. Changes in tone more pronounced than A1   b. Onset/offset not abrupt

A. Absence seizures
1. Typical absence seizure
3. Absence with special features   Myoclonic absence   Eyelid myoclonia

2. Atypical absence seizure

B. Myoclonic seizures

B. 1. Myoclonic seizures
2. Myoclonic atonic seizure
3. Myoclonic tonic seizure

C. Clonic seizures

C. Clonic seizure

D. Tonic seizures

D. Tonic seizure

E. Tonic-clonic seizures

E. Tonic-clonic seizure (in any combination)(no clearly corresponding entity)
F. Atonic seizures

F. Atonic seizure

Unclassified epileptic seizures
Neonatal seizures

Unclassified epileptic seizures
Epileptic spasms

Rhythmic eye movements
Chewing
Swimming movement
Seizures that cannot be clearly diagnosed into one of the above
categories should be considered “unclassified” until additional
information allows their accurate diagnosis. However,“unclassified” is not considered a classification category.
Modified from: Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on
Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1981; 22(4): 489-501.
b
Modified from: Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts of organization of seizures and epilepsies:
Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010; 51(4): 676-685.
a8Part IThe Clinical Practice Guidelines for Epilepsy 2018

Table 2. International classification of epilepsy syndromes: 1989 classification and 2010 revisedclassification.
1989 classification of epilepsy syndromes a
1. Localization-related (focal, local, partial) epilepsies andsyndromes
1.1 Idiopathic (age-related onset)· Benign childhood epilepsy with centrotemporal spikes· Childhood epilepsy with occipital paroxysms· Primary reading epilepsy
1.2 Symptomatic· Chronic progressive epilepsia partialis continua of childhood(Kojewnikow’s syndrome )· Syndromes characterized by seizures with specific modes ofprecipitation· Temporal lobe epilepsies· Frontal lobe epilepsies· Parietal lobe epilepsies· Occipital lobe epilepsies
1.3 Cryptogenic
2. Generalized epilepsies and syndromes
2.1 Idiopathic (with age-related onset - arranged by age)· Benign neonatal familial convulsions· Benign neonatal convulsions· Benign myoclonic epilepsy in infancy· Childhood absence epilepsy (pyknolepsy)· Juvenile absence epilepsy· Juvenile myoclonic epilepsy (impulsive petit mal)
· Epilepsy with grand mal (GTCS) seizures on awakening· Other generalized idiopathic epilepsies not defined above· Epilepsies with seizures precipitated by specific modes ofactivation
2.2 Cryptogenic or symptomatic (arranged by age)· West syndrome (infantile spasm, nodding spasm)· L ennox-Gastaut syndrome· Epilepsy with myoclonic-astatic seizures· Epilepsy with myoclonic absences
2.3 Symptomatic
2.3.1 Non-specific etiology· Early myoclonic encephalopathy· Early infantile epileptic encephalopathy with suppression burst· Other symptomatic generalized epilepsies not defined above
2.3.2 Specific syndromes
3. Epilepsies and syndromes undetermined whether focal or
generalized
3.1 With both generalized and focal seizures· Neonatal seizures· Severe myoclonic epilepsy in infancy· Epilepsy with continuous spike-waves during slow-wave sleep· Acquired epileptic aphasia (Landau-Kleffner syndrome)· Other undetermined epilepsies not defined above
3.2 Without unequivocal generalized or focal features
4. Special syndromes
4.1 Situation-related seizures· Febrile convulsions· Isolated seizures or isolated status epilepticus· Seizures occurring only when there is an acute metabolic or
toxic event such as alcohol, drugs, eclampsia, nonketotic
hyperglycemia, etc.

2010 revised classification of epileptic syndromes b
Electroclinical syndromes (arranged by age at onset) c
Neonatal period   Benign familial neonatal epilepsy   Early myoclonic encephalopathy  Ohtahara syndrome
Infancy
Epilepsy of infancy with migrating focal seizures
West syndrome
Myoclonic epilepsy in infancy
Benign infantile epilepsy
Benign familial infantile epilepsy
Dravet syndrome
Myoclonic encephalopathy in nonprogressive disordersChildhood
Febrile seizures plus (have infancy onset)
Early onset benign childhood occipital epilepsy syndrome(Panayiotopoulos syndrome) Epilepsy with myoclonic atonic (previously astatic) seizures Benign epilepsy with centrotemporal spikes
Autosomal-dominant nocturnal frontal lobe epilepsy Late
onset childhood occipital epilepsy (Gastaut type) Epilepsy with myoclonic absences Lennox-Gastaut syndrome
Epileptic encephalopathy with continuous spike-and-wave
during sleep (CSWS)d Landau-Kleffner syndrome Childhood absence epilepsy
Adolescence-Adult Juvenile absence epilepsy Juvenile myoclonic epilepsy Epilepsy with generalized tonic-clonic seizures alone Progressive myoclonus epilepsies Autosomal dominant epilepsy with auditory features Other familial temporal lobe epilepsies
Less specific age relationship Familial focal epilepsy with variable foci (childhood to adult) Reflex epilepsies
Distinctive constellations Mesial temporal lobe epilepsy with hippocampal sclerosis Rasmussen syndrome Gelastic seizures with hypothalamic hamartoma Hemiconvulsion-hemiplegia-epilepsy
Epilepsy not belonging to these diagnostic categories are
distinguished based on first, presence or absence ofstructural-metabolic disease (presumed cause), and second,mode of seizure onset (generalized vs. focal)
Epilepsies attributed to and organized by structural-metabolic
causes (arranged by etiology)
Malformations of cortical development (hemimegalencephaly,
heterotopias, etc.)
Neurocutaneous syndromes (tuberous sclerosis complex,
Sturge-Weber, etc.) Tumor Infection Trauma
Angioma Perinatal insults Stroke Others
Epilepsies of unknown cause
Conditions with epileptic seizures that are traditionally not
diagnosed as a form of epilepsy per se.
 Benign neonatal seizures Febrile seizures

Modified from: Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminologyof the International League Against Epilepsy. Epilepsia.1989; 30(4): 389-399.
bModified from: Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts of organization of seizures and epilepsies:
Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010; 51(4): 676-685.
cClassification of electroclinical syndromes does not reflect the etiology.
dSometimes also called “electrical status epilepticus during slow sleep (ESES).
a

Chapter 1  

9

CQ 1-4

Which diseases should be differentiated from epilepsy in adults?
Summary
The conditions that may be misdiagnosed as epilepsy are as follows.
(1) Syncope (vasovagal, cardiac, etc.)(2) Psychogenic nonepileptic seizures(3) Hyperventilation or panic disorder(4) Stroke (cerebral infarction, cerebral hemorrhage), transient ischemic attack(5) Parasomnia (REM sleep behavior disorders, non-REM parasomnia)(6) Acute intoxication (drugs, alcohol), drug withdrawal, alcohol withdrawal(7) Acute metabolic disorders (hypoglycemia, tetany, etc.)(8) Acute renal failure(9) Head injury (within one week)(10) Involuntary movements (tic, tremor, myoclonus, paroxysmal dyskinesia, etc.)(11) Episodic ataxia

Comment
Among patients visiting the emergency room with acute onset of loss of consciousness, the most common causes arevasovagal syncope or psychogenic nonepileptic seizure (40%), followed by epilepsy (29%) and cardiac syncope (8%) 1). In the
diagnosis of epilepsy, we should exclude or consider an associated cardiovascular factor 2). A syncope attack is characterized
by no change in consciousness level, fatigue, and malaise after an attack 3, 4). Patients who develop acute convulsion within 1
week after head injury have an overall risk of approximately 25% for developing epilepsy in the future 3). Alcohol withdrawal
may also cause a convulsive attack 3, 4).

▪ References
1) Day SC, Cook EF, Funkenstein H, et al. Evaluation and outcome of emergency room patients with transient loss of consciousness. Am J Med. 1982;
73(1): 15-23.
2) Zaidi A, Clough P, Cooper P, et al. Misdiagnosis of epilepsy: many seizure-like attacks have a cardiovascular cause. J Am Coll Cardiol. 2000; 36(1):181-184.
3) Japanese Society of Neurology Ad Hoc Committee of Treatment Guidelines. Guideline for Treatment of Epilepsy 2002. Rinsho Shinkeigaku. 2002;
42(6): 549-597 (in Japanese).
4) Scottish Intercollegiate Guidelines Network. Diagnosis and management of epilepsy in adults. A national clinical guideline, 2003. p.3-5.

▪ Search formula and secondary reference sources
PubMed search: October 30, 2008((epileptic seizures) or epilepsy) and diagnosis and (distinguish or differentiate or “Diagnosis, Differential” [Mesh]) and (“sensitivity and specificity”[mh] OR sensitivity [tiab] OR specificity [tiab] OR likelihood ratio* OR practice guideline [pt] OR likelihood functions [mh]) and (meta-analysis[mh] OR meta analysis [pt]OR metaanaly* [tiab] OR “meta analysis” OR multicenter study [pt] OR evaluation studies [pt] OR validation studies[pt] OR systematic review* OR systematic [sb]) = 32
No references that could serve as evidence were found in Ichushi Web.
PubMed search: June 28, 2015((((((“Epilepsy” [Major Mesh]) AND “diagnosis, differential” [MeSH Terms]) AND (English [Language] OR Japanese [Language])) AND(“2008”[Date-Publication]: “2015” [Date-Publication])) AND adult [MeSH])) AND (“ILAE” OR “NICE”) = 4
Ichushi search: June 25, 2015(((((epilepsy/MTH)) and (SH = diagnosis)) and (differential diagnosis/TH))) and (DT = 2008:2015 and PT = excluding proceedings and CK = adult(19‒44), middle-aged (45‒64), elderly (65‒), elderly (80‒)) = 3

10Part IThe Clinical Practice Guidelines for Epilepsy 2018

CQ 1-5

Which diseases should be differentiated from epilepsy
in children?
Summary
Confirm that there are no features suggestive of the following pathological conditions. Especially, take history
carefully about the situation before and after the attack. In the case of children, check for fever, crying, diarrhea,
sleep-wake rhythm, and whether the child is hungry.
(1) Febrile convulsion(2) Breath-holding spells(3) Benign convulsions with mild gastroenteritis(4) Convulsion during sleep/sleep myoclonus(5) Non-REM parasomnia (night terror/sleepwalking)(6) Tic(7) Syncope (vasovagal, cardiac, etc.)(8) Psychogenic nonepileptic seizures(9) Masturbation(10) Acute metabolic disorders (hypoglycemia, tetany, etc.)

Comment
In children, some diseases or conditions with paroxysmal symptoms are often misdiagnosed as epileptic seizures. The
symptoms and the diseases/conditions that may show these symptoms are as follows: (1) generalized tonic convulsions andtonic-clonic convulsion: febrile convulsions, benign convulsions with mild gastroenteritis, some psychogenic seizures, acutemetabolic disorders, and prolonged cyanotic breath-holding attacks; (2) loss of consciousness and atonic attack: breathholding spells, vasovagal syncope, some psychogenic seizures, some acute metabolic disorders, and some febrile convulsions;(3) muscle jerks: sleep myoclonus and some psychogenic reactions; (4) strange behaviors such as fear and wandering: night
terror, sleepwalking, and psychogenic reactions. Medical history, symptoms, and onset age help differentiate these diseases
from epilepsy, and EEG examination is sometimes needed 1, 2). Note that some febrile convulsions (especially in children over
3 years of age) or some of the acute metabolic disorders may show epileptic discharges (epileptiform EEG) (Table 1).

▪ References
1) Iinuma K, Fujiwara T, Ikeda A, et al. Japan Epilepsy Society. Task Force on Guideline Committee. Guideline for Diagnosis of Epilepsy. Tenkan
Kenkyu 2008; 26(1): 110-113 (in Japanese).
2) Scottish Intercollegiate Guidelines Network. Diagnosis and management of epilepsy in adults. A national clinical guideline, 2003.

▪ Search formula and secondary reference sources
PubMed search: October 30, 2008((epileptic seizures) or epilepsy) and diagnosis and (distinguish or differentiate or “Diagnosis, Differential” [Mesh]) and (“sensitivity and specificity”[mh] OR sensitivity [tiab] OR specificity [tiab] OR likelihood ratio* OR practice guideline [pt] OR likelihood functions [mh]) and (meta-analysis[mh] OR meta analysis [pt] OR metaanaly* [tiab] OR “meta analysis” OR multicenter study [pt] OR evaluation studies [pt] OR validation studies[pt] OR systematic review* OR systematic [sb]) = 32
No references that could serve as evidence were found in Ichushi Web.
PubMed search: June 28, 2015(((((((“Epilepsy” [Major Mesh]) AND diagnosis, differential [MeSH Terms])) AND (English [Language] OR Japanese [Language])) AND (“2008”[Date-Publication]: “2015” [Date-Publication])) AND “child” [Filter])) AND (“ILAE” OR “NICE”) = 1
Ichushi search: June 25, 2015((((((epilepsy/MTH)) and (SH = diagnosis)) and (differential diagnosis/TH))) and (DT = 2008:2015 and PT = excluding proceedings and CK=
infancy (2‒5), children (6‒12), young adult (13‒18))) and (Japan Epilepsy Society/AL) = 1

Chapter 1  

11

Table 1. Diseases that have to be differentiated from epilepsy in children – benign convulsions andrelated disorders.
Benign convulsion

Seizure symptoms

EEG
abnormality

Diagnosis

Febrile convulsion

Generalized tonic convulsion accompanied by fever of over 38°C;
tonic-clonic convulsions. From medical history and clinicalexaminations, convulsion seems not attributed to central nervous
system infection, metabolic abnormalities, or other obvious
causes. Atonic febrile convulsions such as atonia, staring, andupward rolling of eyeballs 5%; familial onset 20-30%. EEG may
show epileptiform waves.

+/-

Convulsions
occurring only
during fever. No
symptoms
suggestive of otherdisorders.

Breath-holding cyanotic
spellsChild cries uncontrollably due to pain, anger, or bad mood.
Suddenly stops breathing resulting in cyanosis. Loses
consciousness, becomes limp. If prolonged, whole body becomes
tonic.

-

Medical history.
If anxious,
perform EEG

pallidSuddenly loses consciousness without crying, due to sudden pain,
surprise, or fear. Becomes limp, face turns pale.

-

Benign convulsions withmild gastroenteritis

Generalized afebrile tonic-clonic convulsions caused by diarrhea
or vomiting for 2 to 5 days with mild or no dehydration.
Convulsions may be caused by vomiting alone before diarrhea
occurs. If no abnormalities found in EEG and electrolyte tests, thepossibility is high. Commonly seen in rotavirus infection. 80% of
patients show cluster of 2 or more spasms, lasting 2-3 days in20%.

-

Convulsion during sleep /sleep myoclonus

Convulsion during sleep: brief and minor convulsions occurring at
the beginning of sleep; single or repetitive. Although commonly
left-right asymmetric affecting lower limbs, may be seen in upper
limbs and head muscle. Sleep myoclonus: can occur in all sleep
stages, not only asynchronously but also left-right symmetrically;
not only in distal muscles but also in proximal muscles and trunk.

Medical history,
rotavirus antigen
in feces (otherviruses too),(EEG)

Symptoms, timeof occurrence.
If anxious,
perform EEG

Non-REM parasomnia
Night terror: strong fear that happens suddenly during sleep;(night terror/sleepwalking) showing screams, crying, excitement, tachycardia, etc.; lasting 1 to
10 minutes. One-half of patients also show sleepwalking.
Sleepwalking: suddenly rising during sleep, walking or runningaround, etc., lasting 1 to 40 minutes. Both occur during the first
one-third of sleep at night, and are common among 4-12 year-old
children. Do not wake up even when someone tries to wake them.
Patient does not remember the episode. There may be a family
history.

-

Symptoms, timeof occurrence.
If anxious, perform
EEG and poly­somnography

Tic

Abrupt movements noticeable in the face, neck, shoulders, upper
limbs, etc., which repeat regularly and constantly. Also occurs ineyeballs. Increase with mental tension. Does not disturb othermovements while the tic occurs. Does not bother the patient.
Does not occur during sleep.

-

Symptoms

Vasovagal syncope

Suddenly loses consciousness and collapses; becomes atonic. May
be postural dysregulation occurring during postural change or
standing; vagal reflex due to fear and pain; or reflex due to cough,urination, or swallowing. The duration of consciousness loss isshort.

-

Medical history
and symptoms

Psychogenic nonepileptic
seizures

Diverse seizure symptoms, difficult to diagnose from symptoms
alone. Tends to occur under the same situation. Usually does notoccur where nobody is watching. In the case of only psychogenic
reaction, the reaction may be concomitant with epilepsy. Ictal
EEG is necessary for a reliable diagnosis. See the section of“Psychogenic nonepileptic seizure” (CQ14-1 on page 123).

-

Symptoms
Ictal EEG

Masturbation

Repeated motion of extending lower limbs with force over a longtime. Conscious. When looking closely, the thighs and pelvis arerubbing against the bed or something. Symptoms are interrupted
when the thighs are separated. Sometimes red face can be seen.

-

Observe motions
carefully

Acute metabolic disorders(hypoglycemia, tetany,
etc.)

Hypoglycemia may cause loss of consciousness and tonic-clonic
convulsion. Hypocalcemia may cause tonic convulsion or tonicclonic convulsion. Hyponatremia may cause tonic-clonic
convulsion. Hyperammonemia may cause loss of consciousness
and tonic-clonic convulsion.

-/+

Blood glucose,serum calcium,
serum sodium,blood ammonia,
etc.

12

Part IThe Clinical Practice Guidelines for Epilepsy 2018

CQ 1-6

What are the practical procedures for the diagnosis of epilepsy?
Summary
The main procedures of diagnosis of epilepsy are summarized in Figure 1 1). It is recommended that a neurology
specialist should make a definitive clinical diagnosis of epilepsy.

Comment
In patients presenting with the first unprovoked seizures, EEG recording (including photic stimulation, hyperventilation,and sleep) is recommended 1, 2). Sleep-deprived EEG increases the detection rate of epileptic discharges 2). Neuroimaging
study 1) and video-EEG monitoring are necessary.

▪ References
1) Krumholz A, Wiebe S, Gronseth G, et al. Practice Parameter: Evaluating an apparent unprovoked first seizure in adults: Report of the Quality
Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2007; 69(21): 1996-2007.
2) van Donselaar CA, Schimsheimer R-J, Geerts A, et al. Value of the electroencephalogram in adult patients with untreated idiopathic first seizures.
Arch Neurol. 1992; 49(3): 231-237.

▪ Search formula and secondary reference sources
PubMed search: October 30, 2008((epileptic seizures) or epilepsy) and diagnosis and (distinguish or differentiate or “Diagnosis, Differential” [Mesh]) and (“sensitivity and specificity”[mh] OR sensitivity [tiab] OR specificity [tiab] OR likelihood ratio* OR practice guideline [pt] OR likelihood functions [mh]) and (meta-analysis[mh] OR meta analysis [pt] OR metaanaly* [tiab] OR “meta analysis” OR multicenter study [pt] OR evaluation studies [pt] OR validation studies[pt] OR systematic review* OR systematic [sb]) = 32
No references that could serve as evidence were found in Ichushi Web.
PubMed search: June 28, 2015((((epilepsy/diagnosis [majr]) AND diagnosis/methods [majr]) AND ((procedure* OR protocol*)))) AND (“2008” [Date-Publication]: “2015” [DatePublication])) AND (English [Language] OR Japanese [Language]) = 116
Ichushi search: June 25, 2015(((((epilepsy/MTH)) and (SH = diagnosis))) and (DT = 2008:2015 and PT = review)) and (Japan Epilepsy Society/AL) = 2

Figure 1. Procedures for the diagnosis of epilepsy.

Chapter 1  

13