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, altered consciousness, 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 electrical activities 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 the body”, “moving around with loss of consciousness” (see CQ1-4 on page 10, and CQ1-5 on page 11). In addition, epilepsy is characterized by recurrence. Electroencephalography (EEG) has a central role in various examinations and is necessary to establish 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 in special 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 criteria²⁾: (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 of further 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 can be 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⁾_.

▪ 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 Health and 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

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 diagnosis^{1, 2)}.

1. It is important to obtain seizure information from the patient and a witness of the seizure.

a. Frequency of seizure

b. 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 symptoms

e. Symptoms after the seizure

f. Presence or absence of injury, tongue bite and urinary incontinence

g. Headache and muscle pain after seizure

h. Age of the first seizure for a patient with multiple seizures

i. Change and evolution of seizure and type of seizure

j. The last seizure

k. 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 seizure

b. 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 seizure

d. 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. Age (many epilepsies are age-dependent)

b. Sex

c. 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 use

f. Family history

g. Social history

▪ 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 and children 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] OR metaanaly* [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

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 of antiepileptic drugs. The ILAE classifications are widely used. Diagnosis of epilepsy for patients has important significance 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⁾ and the 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 “localization-related”.

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 and syndromes 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 and localized 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 no other 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 in the brain.

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 widely distributed 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 published thereafter are not addressed.

▪ References

1) 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.

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] OR metaanaly* [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

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 are vasovagal 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

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 and tonic-clonic convulsion: febrile convulsions, benign convulsions with mild gastroenteritis, some psychogenic seizures, acute metabolic disorders, and prolonged cyanotic breath-holding attacks; (2) loss of consciousness and atonic attack: breath-holding 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

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” [Date-Publication])) 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