**5. The classification of epilepsies and epileptic syndromes**

An epileptic disorder can be symptomatic, idiopathic, or cryptogenic. Symptomatic is a term that means the etiology is known—usually a structural lesion within the brain. Idiopathic is a term that refers to an epilepsy of presumed genetic etiology without a structural brain lesion or other neurological signs or symptoms. Cryptogenic is a term that refers to an epilepsy that is presumed to be symptomatic but the etiology is unknown (1989). The term cryptogenic has been replaced by "probably symptomatic"(Engel, 2001). The 1989 classification system is divided into four main categories: localization-related (focal, local, or partial), generalized, epilepsies and syndromes undetermined whether focal or generalized, and special syndromes (see Table 2).


	- Chronic progressive epilepsia partialis continua of childhood (Kojewnikow's syndrome)
	- Syndromes characterized by seizures with specific modes of precipitation
	- Temporal lobe epilepsies
	- Frontal lobe epilepsies
	- Parietal lobe epilepsies
	- Occipital lobe epilepsies
	- Benign neonatal familial convulsions
	- Benign neonatal convulsions
	- Benign myoclonic epilepsy in infancy
	- Childhood absence epilepsy
	- West syndrome
	- Lennox-Gastaut syndrome
	- Epilepsy with myoclonic-astatic seizures
	- Epilepsy with myoclonic absences

a brief myoclonic jerk or tonic component. Atypical absence seizures may have an atonic component. The criteria distinguishing between negative myoclonus, atonic seizures, and some atypical absences still needs to be developed (Engel 2006). Atonic seizures are usually seen in the symptomatic generalized epilepsies such as Lennox-Gastaut syndrome. The ictal EEG typically shows a high voltage spike and wave or slow wave followed by a generalized

This category listed in the ILAE's Classification of Epileptic Seizures (1981) includes all seizures that defy classification due to incomplete data. An example is seizure in infancy, which may involve chewing, swimming movements, eye movements, jittering, and apnea,

An epileptic disorder can be symptomatic, idiopathic, or cryptogenic. Symptomatic is a term that means the etiology is known—usually a structural lesion within the brain. Idiopathic is a term that refers to an epilepsy of presumed genetic etiology without a structural brain lesion or other neurological signs or symptoms. Cryptogenic is a term that refers to an epilepsy that is presumed to be symptomatic but the etiology is unknown (1989). The term cryptogenic has been replaced by "probably symptomatic"(Engel, 2001). The 1989 classification system is divided into four main categories: localization-related (focal, local, or partial), generalized, epilepsies and syndromes undetermined whether focal or generalized,

Chronic progressive epilepsia partialis continua of childhood (Kojewnikow's

Syndromes characterized by seizures with specific modes of precipitation

attenuation of cerebral activity or low voltage paroxysmal fast activity.

**5. The classification of epilepsies and epileptic syndromes** 

1. Localization-related epilepsies and syndromes

Primary reading epilepsy

 Temporal lobe epilepsies Frontal lobe epilepsies Parietal lobe epilepsies Occipital lobe epilepsies

2. Generalized epilepsies and syndromes

Benign neonatal convulsions

Childhood absence epilepsy

Benign neonatal familial convulsions

Benign myoclonic epilepsy in infancy

Childhood epilepsy with occipital paroxysms

Benign childhood epilepsy with centrotemporal spikes

**4. Unclassified epileptic seizures** 

and have not yet been subtyped.

and special syndromes (see Table 2).

syndrome)

1.1 Idiopathic

1.2 Symptomatic

1.3 Cryptogenic

2.1 Idiopathic

	- Early myoclonic encephalopathy
	- Early infantile epileptic encephalopathy with suppression burst
	- Other symptomatic generalized epilepsies not defined above
	- Diseases in which seizures are a presenting or predominant feature
	- 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 (i.e. – Sleep related GTCS; when the EEG shows both focal and generalized ictal or interictal discharges, and when focal or generalized onset cannot be determined clinically)

	- Febrile convulsions
	- Isolated seizures or isolated status epilepticus
	- Seizures occurring only when there is an acute metabolic or toxic event (alcohol, drugs, eclampsia, nonketotic hyperglycemia)

Table 2**.** ILAE's 1989 International Classification of Epilepsies and Epileptic Syndromes, from (1989). Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy*. Epilepsia,* Vol. 30, No. 4, (August 1989), pp. 389-99, ISSN 1528-1167

An epilepsy syndrome is defined as "a complex of signs and symptoms that define a unique epilepsy condition" (Engel, 2001). The groups of syndromes are: idiopathic focal epilepsies of infancy and childhood, familial (autosomal dominant) focal epilepsies, symptomatic (or probably symptomatic) focal epilepsies, idiopathic generalized epilepsies, reflex epilepsies, epileptic encephalopathies, progressive myoclonus epilepsies, and seizures not necessarily requiring a diagnosis of epilepsy (see Table 3). There are over 25 specific syndromes in the 1989 ILAE report. A discussion regarding a few of the more common syndromes affecting adolescents and adults follows.

The Classification of Seizures and Epilepsy Syndromes 77

Epileptic encephalopathies Early myoclonic encephalopathy

 Ohtahara syndrome West syndrome Dravet syndrome

Progressive myoclonic epilepsies Ceroid lipofuscinosis

 Sialidosis Lafora disease

MERRF

 Febrile seizures Reflex seizures

Seizures not necessarily requiring a

diagnosis of epilepsy

\* Syndromes in development

pp. 796-803, ISSN 1528-1167

**5.1 Temporal lobe epilepsies** 

 Lennox-Gastaut syndrome Landau-Kleffner syndrome

 Unverricht-Lundborg disease Neuroaxonal dystrophy

Alcohol-withdrawal seizures

Dentatorubropallidoluysian atrophy

Table 3. An Example of a Classification of Epilepsy Syndromes, from Engel, J., Jr. (2001). A proposed diagnostic scheme for People with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. *Epilepsia*, Vol.42, No. 6, (June 2001),

Temporal lobe seizures are the most common type of partial epilepsy. Temporal lobe seizures often begin with an aura (Quesney, 1986). Auras may include viscerosensory symptoms (epigastric sensation, thoracic sensation, and warm ascending sensation) or sensory illusions or hallucinations. The ictal event is usually characterized by a blank stare, loss of contact with the environment, oroalimentary or vocal automatisms, hand automatisms, upper limb tonic or dystonic posturing, early head or eye deviation, and dysphasia. Oroalimentary automatisms are defined as stereotyped, repetitive movements of the mouth, tongue, lips, or jaw which have the appearance of chewing or lip-smacking. They may also involve gulping, swallowing, or spitting. Hand automatisms are repetitive, purposeless movements of the hands including grasping, fumbling, and searching movements. Both oroalimentary and hand automatisms often localize to the mesial temporal lobe. Table 4 lists other ictal signs with localizing and lateralizing value. In terms

**Specific syndromes** 

slow-wave sleep

Benign neonatal seizures

Epilepsy with continuous spike-waves during

Drug or other chemically induced seizures Immediate and early posttraumatic seizures Single seizures or isolated clusters of seizures Rarely repeated seizures (oligoepilepsy)

**Groups of syndromes** 


**Specific syndromes** 

epilepsy

Limbic epilepsies

etiology

etiology

infancy\*

phenotypes

Generalized epilepsies with febrile seizures plus\*

epilepsy

Reflex epilepsies Idiopathic photosensitive occipital lobe

Startle epilepsy

Neocortical epilepsies

Idiopathic generalized epilepsies Benign myoclonic epilepsy in infancy

epilepsy

Benign infantile seizures

 Benign childhood epilepsy with centrotemporal spikes

Benign familial neonatal seizures

Benign familial infantile seizures

Familial temporal lobe epilepsy

hippocampal sclerosis

specific etiologies

Rasmussen syndrome

Childhood absence epilepsy Epilepsy with myoclonic absences

 Juvenile absence epilepsy Juvenile myoclonic epilepsy Epilepsy with GTCS only

Other visual sensitive epilepsies Primary reading epilepsy

Early-onset benign childhood occipital

Late-onset childhood occipital epilepsy

Autosomal dominant nocturnal frontal lobe

Familial focal epilepsy with variable foci\*

Mesial temporal lobe epilepsy with

Other types defined by location and

 Hemiconvulsion-hemiplegia syndrome Other types defined by location and

Migrating partial seizures of early

Epilepsy with myoclonic astatic seizures

Idiopathic generalized epilepsies with variable

Mesial temporal lobe epilepsy defined by

**Groups of syndromes** 

and childhood

epilepsies

Idiopathic focal epilepsies of infancy

Familial (autosomal dominant) focal

Symptomatic (or probably symptomatic) focal epilepsies


\* Syndromes in development

Table 3. An Example of a Classification of Epilepsy Syndromes, from Engel, J., Jr. (2001). A proposed diagnostic scheme for People with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. *Epilepsia*, Vol.42, No. 6, (June 2001), pp. 796-803, ISSN 1528-1167

#### **5.1 Temporal lobe epilepsies**

Temporal lobe seizures are the most common type of partial epilepsy. Temporal lobe seizures often begin with an aura (Quesney, 1986). Auras may include viscerosensory symptoms (epigastric sensation, thoracic sensation, and warm ascending sensation) or sensory illusions or hallucinations. The ictal event is usually characterized by a blank stare, loss of contact with the environment, oroalimentary or vocal automatisms, hand automatisms, upper limb tonic or dystonic posturing, early head or eye deviation, and dysphasia. Oroalimentary automatisms are defined as stereotyped, repetitive movements of the mouth, tongue, lips, or jaw which have the appearance of chewing or lip-smacking. They may also involve gulping, swallowing, or spitting. Hand automatisms are repetitive, purposeless movements of the hands including grasping, fumbling, and searching movements. Both oroalimentary and hand automatisms often localize to the mesial temporal lobe. Table 4 lists other ictal signs with localizing and lateralizing value. In terms

The Classification of Seizures and Epilepsy Syndromes 79

sclerosis) may be able to speak normally during the seizure. Patients with left temporal lobe seizures due to MTS often make prominent paraphasic errors during and after seizures. Specific semiological features are also helpful in distinguishing between mesial, mesiallateral, and lateral temporal lobe epilepsy. Mesial temporal lobe seizures are often characterized by an initial epigastric sensation or viscerosensory sensation, fear, a dreamy state, longer seizure duration, delayed loss of contact, and delayed oroalimentary and upper limb automatisms while lateral temporal lobe seizures are characterized by an initial sensory illusion or hallucination (mainly auditory), an initial loss of contact, a shorter duration (< 1 minute), and frequent secondary generalizations. The mesial-lateral temporal lobe seizures were similar to the mesial temporal seizures but had an earlier loss of contact and earlier oroalimentary, verbal, and vocal automatisms (Maillard et al., 2004). It is important to distinguish between mesial (limbic) and lateral (neocortical) temporal lobe epilepsy if one is considering a surgical option such as a temporal lobectomy, as

Frontal lobe seizures are the second most common type of focal epilepsy and occur in approximately 30% of patients with partial epilepsy (Bancaud & Talairach, 1992). Frontal lobe seizures are often confused with pseudoseizures due to the bizarre clinical semiology. Frontal lobe seizures are usually brief (less than 30 seconds), tend to occur in clusters, can occur multiple times per day, and often have minimal or no post-ictal confusion. The clinical semiology includes an abrupt onset of stereotyped hypermotor behavior and may include vocalizations, gestural or sexual automatisms, and bilateral leg automatisms consisting of pedaling or bicycling movements. The seizure semiology of frontal lobe seizures varies depending on what region of the frontal lobe is involved. The patient may have asymmetric tonic extension of the proximal extremities, as in SMA seizures, or clonic activity of the contralateral limb, as in seizures from the lateral convexity. Seizures originating from the mesial frontal region or SMA are characterized by vocalizations and abrupt tonic extension of the proximal extremities which may be bilateral and is often asymmetric. There is minimal impairment of consciousness or post-ictal confusion. Lateral dorsal frontal lobe seizures are characterized by speech arrest, forced thinking, contraversive head and eye deviation, and automatisms such as laughing, crying, sniffing, chewing, or kicking. Orbitofrontal seizures are characterized by prominent autonomic symptoms (flushing, mydriasis, tachycardia), automatisms, and loud vocalizations. They can also appear similar to mesial temporal lobe seizures due to rapid spread to this region. Cingulate gyrus seizures are similar to SMA seizures but also involve behavioral arrest, oroalimentary automatisms, gestural or sexual automatisms, mood changes, and sometimes urinary incontinence. Because of the extensive inter-regional connectivity within the frontal lobe and rapid seizure propagation, frontal lobe seizures are difficult to localize on the basis

Parietal lobe seizures account for < 10% of focal seizures. Often they arise from clinically silent areas and only manifest symptoms when the seizure spreads to other functional cortical regions. They can spread to the occipital, temporal, or frontal regions. Clinically,

postsurgical seizure-freedom and complication rates differ.

**5.2 Frontal lobe epilepsies** 

of clinical semiology.

**5.3 Parietal lobe epilepsies** 

of lateralization (determining right vs. left hemispheric involvement), unilateral automatisms and post-ictal dysphasia were determined to have the highest predicative value. Unilateral automatisms are typically ipsilateral to region of seizure onset, and postictal dysphasia lateralized to the dominant hemisphere (Chee et al., 1993). Nondominant temporal lobe seizures can have preservation of language and responsiveness with minimal post-ictal confusion. Patients with right temporal lobe epilepsy due to MTS (mesial temporal


Table 4. Localization and Lateralization of Ictal Seizure Semiology

sclerosis) may be able to speak normally during the seizure. Patients with left temporal lobe seizures due to MTS often make prominent paraphasic errors during and after seizures. Specific semiological features are also helpful in distinguishing between mesial, mesiallateral, and lateral temporal lobe epilepsy. Mesial temporal lobe seizures are often characterized by an initial epigastric sensation or viscerosensory sensation, fear, a dreamy state, longer seizure duration, delayed loss of contact, and delayed oroalimentary and upper limb automatisms while lateral temporal lobe seizures are characterized by an initial sensory illusion or hallucination (mainly auditory), an initial loss of contact, a shorter duration (< 1 minute), and frequent secondary generalizations. The mesial-lateral temporal lobe seizures were similar to the mesial temporal seizures but had an earlier loss of contact and earlier oroalimentary, verbal, and vocal automatisms (Maillard et al., 2004). It is important to distinguish between mesial (limbic) and lateral (neocortical) temporal lobe epilepsy if one is considering a surgical option such as a temporal lobectomy, as postsurgical seizure-freedom and complication rates differ.

#### **5.2 Frontal lobe epilepsies**

78 Novel Aspects on Epilepsy

of lateralization (determining right vs. left hemispheric involvement), unilateral automatisms and post-ictal dysphasia were determined to have the highest predicative value. Unilateral automatisms are typically ipsilateral to region of seizure onset, and postictal dysphasia lateralized to the dominant hemisphere (Chee et al., 1993). Nondominant temporal lobe seizures can have preservation of language and responsiveness with minimal post-ictal confusion. Patients with right temporal lobe epilepsy due to MTS (mesial temporal

Ipsilateral temporal

Frontal

Focal clonic Contralateral peri-rolandic or temporal Dystonic limb Contralateral temporal > frontal Unilateral tonic limb Contralateral hemisphere M2e sign (fencing posture) Contralateral frontal > temporal

Ictal paresis Contralateral hemisphere

Unilateral blinking Ipsilateral hemisphere

Bipedal automatisms Frontal > temporal

Ictal spitting Right temporal Automatisms with preserved Right temporal

Ictal vomiting/retching Right temporal

Ictal speech arrest Temporal

Postictal cough Temporal

Figure 4 Contralateral hemisphere (to extended arm)

Todd's paresis Contralateral hemisphere (extratemporal > temporal)

Postictal nose rubbing Ipsilateral temporal > frontal (to hand used)

Hypermotor SMA (supplementary motor area)

Gelastic Hypothalamic, mesial temporal

Ictal urinary urge Non-dominant temporal Loud vocalization Frontal > temporal

Ictal speech preservation Non-dominant hemisphere Post-ictal aphasia Language-dominant hemisphere

Table 4. Localization and Lateralization of Ictal Seizure Semiology

Late forced Contralateral temporal (in process of generalizing)

Contralateral occipital

Ipsilateral hemisphere

**Clinical Event Localization/Lateralization**

Head turn

Forced

Ocular version

Early non-forced

Early forced

Unilateral limb automatism

responsiveness

Frontal lobe seizures are the second most common type of focal epilepsy and occur in approximately 30% of patients with partial epilepsy (Bancaud & Talairach, 1992). Frontal lobe seizures are often confused with pseudoseizures due to the bizarre clinical semiology. Frontal lobe seizures are usually brief (less than 30 seconds), tend to occur in clusters, can occur multiple times per day, and often have minimal or no post-ictal confusion. The clinical semiology includes an abrupt onset of stereotyped hypermotor behavior and may include vocalizations, gestural or sexual automatisms, and bilateral leg automatisms consisting of pedaling or bicycling movements. The seizure semiology of frontal lobe seizures varies depending on what region of the frontal lobe is involved. The patient may have asymmetric tonic extension of the proximal extremities, as in SMA seizures, or clonic activity of the contralateral limb, as in seizures from the lateral convexity. Seizures originating from the mesial frontal region or SMA are characterized by vocalizations and abrupt tonic extension of the proximal extremities which may be bilateral and is often asymmetric. There is minimal impairment of consciousness or post-ictal confusion. Lateral dorsal frontal lobe seizures are characterized by speech arrest, forced thinking, contraversive head and eye deviation, and automatisms such as laughing, crying, sniffing, chewing, or kicking. Orbitofrontal seizures are characterized by prominent autonomic symptoms (flushing, mydriasis, tachycardia), automatisms, and loud vocalizations. They can also appear similar to mesial temporal lobe seizures due to rapid spread to this region. Cingulate gyrus seizures are similar to SMA seizures but also involve behavioral arrest, oroalimentary automatisms, gestural or sexual automatisms, mood changes, and sometimes urinary incontinence. Because of the extensive inter-regional connectivity within the frontal lobe and rapid seizure propagation, frontal lobe seizures are difficult to localize on the basis of clinical semiology.

#### **5.3 Parietal lobe epilepsies**

Parietal lobe seizures account for < 10% of focal seizures. Often they arise from clinically silent areas and only manifest symptoms when the seizure spreads to other functional cortical regions. They can spread to the occipital, temporal, or frontal regions. Clinically,

The Classification of Seizures and Epilepsy Syndromes 81

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a symptomatic focal epilepsy and subcategorized as a limbic epilepsy (vs. neocortical epilepsy). Mesial temporal lobe epilepsy is one of the most common types of epilepsy referred for epilepsy surgery and is often refractory to AEDs. The age of onset is between late childhood to mid adolescence. Patients often had febrile convulsions in infancy or early childhood. Most patients report an aura. Common auras include an epigastric sensation (a rising sensation, butterflies, nausea), fear, olfactory hallucinations, lightheadedness, and déjà vu (French et al., 1993). Complex partial seizure semiology may also consist of ipsilateral upper extremity automatisms and ipsilateral early non-forced head turn. Contralateral dystonic posturing, Todd's paralysis, and

Hippocampal sclerosis is the most common pathological substrate found in patients with medial temporal lobe epilepsy who undergo surgical resection. Hippocampal sclerosis is strongly associated with prolonged febrile seizures in childhood, but the cause is still unknown. The majority of patients who undergo surgical resection for MTLE-HS become seizure free (Ozkara et al., 2008). Is an example of a patient with right mesial temporal

Juvenile absence epilepsy (JAE) is classified as an idiopathic generalized epilepsy. The age of onset is typically at or after puberty between the ages of 10-17. Unlike in childhood absence epilepsy (CAE) where absence seizures can occur hundreds of times per day, absence seizures in JAE may only occur sporadically. There is less impairment of consciousness with absence seizures in JAE compared to absences in CAE. Patients with JAE can have generalized tonic-clonic seizures (usually upon awakening), myoclonic seizures, and even absence status epilepticus. The ictal EEG pattern resembles that of CAE (3 Hz spike and wave) but the discharges tend to vary slightly in frequency (usually > 3 Hz), are more irregular, and include more polyspike discharges. There is a strong genetic component with linkage to chromosomes 5, 8, 18, and 21. The response to antiepileptic medication is

Juvenile Myoclonic Epilepsy (JME) is also classified as an idiopathic generalized epilepsy. The age of onset is in the mid-teens between the ages of 12-18. Patients may present with myoclonic jerks upon awakening in the morning. Patients may first ignore the myoclonic jerks, often attributing them to clumsiness. Sometimes the diagnosis is not made until the patient has a generalized tonic-clonic seizure. The myoclonus usually involves the neck, shoulders, arms, or legs with the upper extremities being more frequently affected. Consciousness is usually not impaired during the myoclonic seizures. Generalized tonicclonic and absence seizures are also seen. Generalized tonic-clonic seizures may also occur in the morning upon awakening and can be triggered by sleep deprivation, alcohol, and stress. Often, several myoclonic jerks may precede a generalized tonic-clonic seizure, which is known as a clonic-tonic-clonic seizure. Approximately 50% of patients can be photosensitive. The ictal EEG consists of generalized polyspike and wave discharges > 3 Hz. There is a strong genetic component with linkage to chromosomes 2, 3, 5, 6, and 15. The response to AED treatment is excellent but needs to be continued lifelong in most patients

**5.7 Mesial temporal lobe epilepsy with hippocampal sclerosis** 

late forced head turn prior to secondary generalization can also be seen.

sclerosis who was rendered seizure-free after a right temporal lobectomy.

**5.8 Juvenile absence epilepsy** 

usually excellent (Beghi et al., 2006).

**5.9 Juvenile myoclonic epilepsy** 

due to a high rate of relapse (Beghi et al., 2006).

patients may report somatosensory symptoms, most commonly in the face and hand, contralateral to the seizure focus. In nondominant parietal lobe seizures, patients can have spatial neglect of the contralateral body or environment. In dominant parietal lobe seizures, patients may have language dysfunction.

#### **5.4 Occipital lobe epilepsies**

Occipital lobe seizures also account for < 10% of focal seizures. They are characterized by elementary visual hallucinations of fixed or moving flashing white or colored lights which start in the contralateral visual field and can spread to the entire visual field. Patients may also report a "whiting out" or "blacking out" of their vision. The eyes may deviate contralaterally, and the eyelids may rapidly blink. The remainder of the seizure is characterized by where the seizure discharge spreads. If the seizure spreads to the posterior temporal region (area of visual association cortex), complex visual hallucinations may occur. Occipital seizures may also spread to the mesial temporal, parietal, and perirolandic regions and mimic seizures of those regions.

#### **5.5 Autosomal dominant nocturnal frontal lobe epilepsy**

Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) is a familial autosomal dominant focal epilepsy characterized by clusters of brief seizures (5-30 seconds) during NREM sleep (stages N2 and N3). They are often initially misdiagnosed as nightmares or parasomnias. The mean age of onset is around 12 years of age (range 1-30). The seizures themselves are characterized by brief motor attacks, usually with a dystonic or dyskinetic component. During a seizure patients may have complex and bizarre behaviors, shouting, bimanual and bipedal automatisms, mumbling, urinary incontinence, and rarely violent behavior. The ictal EEG may demonstrate a frontally predominant ictal discharge in approximately 30% of patients and focal background attenuation or focal rhythmic slowing over the anterior head regions in about 55% of patients (Oldani et al., 1998). The CHRNA4 gene on chromosome 20, which encodes the neuronal nicotinic acetylcholine receptor (nAChR) alpha 4 subunit, is mutated in patients with ADNFLE type 1. The CHRNB2 gene on chromosome 1 is mutated in patients with ADNFLE type 3. The molecular pathogenesis of how these mutations cause ADNFLE is unknown (Hirose et al., 2005).

#### **5.6 Autosomal dominant partial epilepsy with auditory features**

Autosomal Dominant Partial Epilepsy with Auditory Features (ADPEAF) or Autosomal Dominant Lateral Temporal Epilepsy (ADLTE) is also a familial autosomal dominant focal epilepsy characterized by lateral temporal lobe epilepsy and auditory aura. It is due to a mutation in the LGI1 gene (leucine-rich glioma-inactivated 1 gene) which is expressed in neurons in the neocortex and limbic regions (Hirose et al., 2005). Mutations in the LGI1 gene have been found in 50% of families with this type of epilepsy (Ottman et al., 2004). The age of onset is between 1 and 60 years with a mean of 18 years. The seizures are characterized by auditory auras (64%), complex visual (17%), psychic (16%), autonomic (12%), vertiginous (9%), other sensory (13% ), and aphasia (17%). The majority of auditory auras are simple in nature (humming, buzzing, ringing). A minority of patients report complex hallucinations such as music or voices. The MRI of the brain is normal, and patients typically have a good response to treatment with antiepileptic drugs (Michelucci, 2003, 2009).

patients may report somatosensory symptoms, most commonly in the face and hand, contralateral to the seizure focus. In nondominant parietal lobe seizures, patients can have spatial neglect of the contralateral body or environment. In dominant parietal lobe seizures,

Occipital lobe seizures also account for < 10% of focal seizures. They are characterized by elementary visual hallucinations of fixed or moving flashing white or colored lights which start in the contralateral visual field and can spread to the entire visual field. Patients may also report a "whiting out" or "blacking out" of their vision. The eyes may deviate contralaterally, and the eyelids may rapidly blink. The remainder of the seizure is characterized by where the seizure discharge spreads. If the seizure spreads to the posterior temporal region (area of visual association cortex), complex visual hallucinations may occur. Occipital seizures may also spread to the mesial temporal, parietal, and perirolandic regions

Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) is a familial autosomal dominant focal epilepsy characterized by clusters of brief seizures (5-30 seconds) during NREM sleep (stages N2 and N3). They are often initially misdiagnosed as nightmares or parasomnias. The mean age of onset is around 12 years of age (range 1-30). The seizures themselves are characterized by brief motor attacks, usually with a dystonic or dyskinetic component. During a seizure patients may have complex and bizarre behaviors, shouting, bimanual and bipedal automatisms, mumbling, urinary incontinence, and rarely violent behavior. The ictal EEG may demonstrate a frontally predominant ictal discharge in approximately 30% of patients and focal background attenuation or focal rhythmic slowing over the anterior head regions in about 55% of patients (Oldani et al., 1998). The CHRNA4 gene on chromosome 20, which encodes the neuronal nicotinic acetylcholine receptor (nAChR) alpha 4 subunit, is mutated in patients with ADNFLE type 1. The CHRNB2 gene on chromosome 1 is mutated in patients with ADNFLE type 3. The molecular pathogenesis

Autosomal Dominant Partial Epilepsy with Auditory Features (ADPEAF) or Autosomal Dominant Lateral Temporal Epilepsy (ADLTE) is also a familial autosomal dominant focal epilepsy characterized by lateral temporal lobe epilepsy and auditory aura. It is due to a mutation in the LGI1 gene (leucine-rich glioma-inactivated 1 gene) which is expressed in neurons in the neocortex and limbic regions (Hirose et al., 2005). Mutations in the LGI1 gene have been found in 50% of families with this type of epilepsy (Ottman et al., 2004). The age of onset is between 1 and 60 years with a mean of 18 years. The seizures are characterized by auditory auras (64%), complex visual (17%), psychic (16%), autonomic (12%), vertiginous (9%), other sensory (13% ), and aphasia (17%). The majority of auditory auras are simple in nature (humming, buzzing, ringing). A minority of patients report complex hallucinations such as music or voices. The MRI of the brain is normal, and patients typically have a good

patients may have language dysfunction.

**5.4 Occipital lobe epilepsies** 

and mimic seizures of those regions.

**5.5 Autosomal dominant nocturnal frontal lobe epilepsy** 

of how these mutations cause ADNFLE is unknown (Hirose et al., 2005).

**5.6 Autosomal dominant partial epilepsy with auditory features** 

response to treatment with antiepileptic drugs (Michelucci, 2003, 2009).

#### **5.7 Mesial temporal lobe epilepsy with hippocampal sclerosis**

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a symptomatic focal epilepsy and subcategorized as a limbic epilepsy (vs. neocortical epilepsy). Mesial temporal lobe epilepsy is one of the most common types of epilepsy referred for epilepsy surgery and is often refractory to AEDs. The age of onset is between late childhood to mid adolescence. Patients often had febrile convulsions in infancy or early childhood. Most patients report an aura. Common auras include an epigastric sensation (a rising sensation, butterflies, nausea), fear, olfactory hallucinations, lightheadedness, and déjà vu (French et al., 1993). Complex partial seizure semiology may also consist of ipsilateral upper extremity automatisms and ipsilateral early non-forced head turn. Contralateral dystonic posturing, Todd's paralysis, and late forced head turn prior to secondary generalization can also be seen.

Hippocampal sclerosis is the most common pathological substrate found in patients with medial temporal lobe epilepsy who undergo surgical resection. Hippocampal sclerosis is strongly associated with prolonged febrile seizures in childhood, but the cause is still unknown. The majority of patients who undergo surgical resection for MTLE-HS become seizure free (Ozkara et al., 2008). Is an example of a patient with right mesial temporal sclerosis who was rendered seizure-free after a right temporal lobectomy.

#### **5.8 Juvenile absence epilepsy**

Juvenile absence epilepsy (JAE) is classified as an idiopathic generalized epilepsy. The age of onset is typically at or after puberty between the ages of 10-17. Unlike in childhood absence epilepsy (CAE) where absence seizures can occur hundreds of times per day, absence seizures in JAE may only occur sporadically. There is less impairment of consciousness with absence seizures in JAE compared to absences in CAE. Patients with JAE can have generalized tonic-clonic seizures (usually upon awakening), myoclonic seizures, and even absence status epilepticus. The ictal EEG pattern resembles that of CAE (3 Hz spike and wave) but the discharges tend to vary slightly in frequency (usually > 3 Hz), are more irregular, and include more polyspike discharges. There is a strong genetic component with linkage to chromosomes 5, 8, 18, and 21. The response to antiepileptic medication is usually excellent (Beghi et al., 2006).

#### **5.9 Juvenile myoclonic epilepsy**

Juvenile Myoclonic Epilepsy (JME) is also classified as an idiopathic generalized epilepsy. The age of onset is in the mid-teens between the ages of 12-18. Patients may present with myoclonic jerks upon awakening in the morning. Patients may first ignore the myoclonic jerks, often attributing them to clumsiness. Sometimes the diagnosis is not made until the patient has a generalized tonic-clonic seizure. The myoclonus usually involves the neck, shoulders, arms, or legs with the upper extremities being more frequently affected. Consciousness is usually not impaired during the myoclonic seizures. Generalized tonicclonic and absence seizures are also seen. Generalized tonic-clonic seizures may also occur in the morning upon awakening and can be triggered by sleep deprivation, alcohol, and stress. Often, several myoclonic jerks may precede a generalized tonic-clonic seizure, which is known as a clonic-tonic-clonic seizure. Approximately 50% of patients can be photosensitive. The ictal EEG consists of generalized polyspike and wave discharges > 3 Hz. There is a strong genetic component with linkage to chromosomes 2, 3, 5, 6, and 15. The response to AED treatment is excellent but needs to be continued lifelong in most patients due to a high rate of relapse (Beghi et al., 2006).

The Classification of Seizures and Epilepsy Syndromes 83

report is an update and revision to the classification schemes which are now several decades old. It was devised to simplify the classification of seizures, as new concepts have emerged broadening our understanding of seizures and epilepsy syndromes. The 2010 ILAE report on revised terminology and concepts for organization of seizures and epilepsies is not a new classification of epilepsies but rather a reflection of new terminology and concepts that lead to a better understanding of the current neurobiology, clinical features, prognostic implications, and features relevant to clinical practice and research. The ILAE did not feel that there was adequate knowledge at this time to propose a new classification of seizures and the epilepsies. The following paragraphs are a summary of the ILAE's report on

The new definition of generalized epileptic seizures is "originating at some point within, and rapidly engaging, bilaterally distributed networks" which include both cortical and subcortical structures, can appear localized but have inconsistent localization and lateralization, and can be asymmetric. Focal epileptic seizures originate "within networks limited to one hemisphere" and can originate in subcortical structures, can be localized or

There have been a few changes to the 1981 ILAE classification of seizures. First, neonatal seizures are no longer classified as a separate entity. Secondly, the subclassification of absence seizures was simplified to either typical, atypical, or absence with special features which now included myoclonic absence and eyelid myoclonia. Thirdly, epileptic spasms which were not previously acknowledged in the 1981 seizure classification are now included. It is still unknown whether epileptic spasms are focal in onset, generalized in onset, or both so they are classified as "unknown." Fourth, the distinction between simple partial and complex partial focal seizures was eliminated, however, the concept of impairment of consciousness/awareness is still recognized. Lastly, myoclonic astatic

Focal seizures should be described according to their specific elemental features and sequence of occurrence. The glossary of ictal semiology (Blume, et al., 2001) should be consulted for clearly defined and recommended descriptors. For example, the term

The term idiopathic is replaced by the term "genetic." The epilepsy must be a direct result of a known or presumed genetic defect and the seizures a core symptom of the disorder. An example would be Dravet syndrome due to a mutation in the SCN1A mutation. Classifying an epilepsy as genetic does not exclude the possibility that environmental factors may

The term symptomatic is replaced by the term "structural/metabolic." To be classified in this category, the epilepsy has to be associated with a structural lesion or metabolic disease that has been shown in previous studies to substantially increase the risk of developing

"dyscognitive" corresponds to the old term complex partial seizure. (see Table 6).

widely distributed, , and have a consistent site of ictal onset (Berg et al., 2010).

classification and terminology from 2010 (Berg et al., 2010).

**6.2 Changes to the ILAE's 1981 classification of seizures** 

seizures are now termed "myoclonic atonic" seizures. (see Table 5).

**6.4 Replacing idiopathic, symptomatic, and cryptogenic** 

**6.1 Generalized and focal redefined** 

**6.3 Focal seizures should be described** 

contribute to expression of the disease.

#### **5.10 Epilepsy with generalized tonic clonic seizures (GTCS) on awakening**

This syndrome is also known as Epilepsy with generalized tonic-clonic seizures only and is classified as one of the idiopathic generalized epilepsies. The age of onset is the second decade of life. GTCS occur > 90% of the time, with absence and myoclonic seizures occurring less frequently. Seizures occur 1-2 hours after awakening from sleep or during periods of relaxation in the evening. Sleep deprivation, alcohol, and photic stimulation can be precipitating factors. The ictal EEG demonstrates frontally predominant fast rhythmic spiking. The prognosis is good if the patient is adequately treated with AED's and avoids provoking factors (1989; Beghi et al., 2006).

#### **5.11 Lennox-Gastaut syndrome**

Lennox-Gastaut Syndrome (LGS) is classified as an epileptic encephalopathy. The age of onset is usually before age 8 with a peak age of onset between 3-5 years of age. Rarely, the disorder can present in early adulthood. The syndrome is characterized by a triad of multiple seizure types (tonic and atypical absence are the most common), slow spike and wave on EEG (1-2.5 Hz), and some degree of mental retardation. The etiology can be symptomatic or cryptogenic. It may evolve from West syndrome. Tonic seizures are considered a prerequisite for the diagnosis. Atypical absence and atonic seizures are also common. Myoclonic, generalized tonic-clonic, unilateral clonic, and partial seizures can occur less frequently. Non-convulsive status epilepticus can occur in > 50% of patients and involves near continuous atypical absence seizures interrupted by brief tonic seizures. The interictal EEG is characterized by slow spike and wave complexes (< 2.5 Hz) and activation of generalized paroxysmal fast activity during sleep. The diagnosis may be difficult to make at first because not all features of the syndrome may be present. The seizures in LGS are typically refractory to medical treatment (Arzimanoglou et al., 2009).

#### **5.12 Progressive myoclonic epilepsies (PME)**

These diseases are characterized by myoclonic jerks, seizures (GTC, absence, clonic, partial) and dementia caused by cerebral and cerebellar atrophy. The myoclonus is termed "massive myoclonus" which can cause falls and lead into generalized tonic-clonic seizures. Patients may exhibit cerebellar dysfunction, action myoclonus, or extrapyramidal dysfunction. Childhood development is normal until the age of onset. The autosomal recessive forms include Lafora disease, Unverricht-Lundborg disease, the neuronal ceroid lipofuscinoses , sialidosis, Action Myoclonus-Renal Failure Syndrome (AMRF), and Gaucher disease. The autosomal dominant form is dentatorubropallidolluysan atrophy. PME is also seen in some mitochondrial cytopathies such as myoclonic epilepsy with ragged-red fibers (MERRF).

#### **6. 2010 ILAE commission on classification and terminology report**

The 1981 and 1989 ILAE classifications are based on concepts formulated prior to modern neuroimaging and genomic research. The 1989 classification was not a true scientific classification but rather an organized list built on concepts which no longer correspond to or accurately describe our increasing knowledge of seizures and the epilepsies. Numerous attempts have been made by the ILAE Committee (Engel, 2001, 2006) and individual investigators (Luders et al., 1998) to revise the current classification. These attempts have generated controversy, and the lack of consensus has blocked any formal revision until 2010 (Berg et al., 2010). The most recent ILAE Commission on Classification and Terminology

This syndrome is also known as Epilepsy with generalized tonic-clonic seizures only and is classified as one of the idiopathic generalized epilepsies. The age of onset is the second decade of life. GTCS occur > 90% of the time, with absence and myoclonic seizures occurring less frequently. Seizures occur 1-2 hours after awakening from sleep or during periods of relaxation in the evening. Sleep deprivation, alcohol, and photic stimulation can be precipitating factors. The ictal EEG demonstrates frontally predominant fast rhythmic spiking. The prognosis is good if the patient is adequately treated with AED's and avoids

Lennox-Gastaut Syndrome (LGS) is classified as an epileptic encephalopathy. The age of onset is usually before age 8 with a peak age of onset between 3-5 years of age. Rarely, the disorder can present in early adulthood. The syndrome is characterized by a triad of multiple seizure types (tonic and atypical absence are the most common), slow spike and wave on EEG (1-2.5 Hz), and some degree of mental retardation. The etiology can be symptomatic or cryptogenic. It may evolve from West syndrome. Tonic seizures are considered a prerequisite for the diagnosis. Atypical absence and atonic seizures are also common. Myoclonic, generalized tonic-clonic, unilateral clonic, and partial seizures can occur less frequently. Non-convulsive status epilepticus can occur in > 50% of patients and involves near continuous atypical absence seizures interrupted by brief tonic seizures. The interictal EEG is characterized by slow spike and wave complexes (< 2.5 Hz) and activation of generalized paroxysmal fast activity during sleep. The diagnosis may be difficult to make at first because not all features of the syndrome may be present. The seizures in LGS are

These diseases are characterized by myoclonic jerks, seizures (GTC, absence, clonic, partial) and dementia caused by cerebral and cerebellar atrophy. The myoclonus is termed "massive myoclonus" which can cause falls and lead into generalized tonic-clonic seizures. Patients may exhibit cerebellar dysfunction, action myoclonus, or extrapyramidal dysfunction. Childhood development is normal until the age of onset. The autosomal recessive forms include Lafora disease, Unverricht-Lundborg disease, the neuronal ceroid lipofuscinoses , sialidosis, Action Myoclonus-Renal Failure Syndrome (AMRF), and Gaucher disease. The autosomal dominant form is dentatorubropallidolluysan atrophy. PME is also seen in some mitochondrial cytopathies such as myoclonic epilepsy with ragged-red fibers (MERRF).

The 1981 and 1989 ILAE classifications are based on concepts formulated prior to modern neuroimaging and genomic research. The 1989 classification was not a true scientific classification but rather an organized list built on concepts which no longer correspond to or accurately describe our increasing knowledge of seizures and the epilepsies. Numerous attempts have been made by the ILAE Committee (Engel, 2001, 2006) and individual investigators (Luders et al., 1998) to revise the current classification. These attempts have generated controversy, and the lack of consensus has blocked any formal revision until 2010 (Berg et al., 2010). The most recent ILAE Commission on Classification and Terminology

**6. 2010 ILAE commission on classification and terminology report** 

**5.10 Epilepsy with generalized tonic clonic seizures (GTCS) on awakening** 

typically refractory to medical treatment (Arzimanoglou et al., 2009).

**5.12 Progressive myoclonic epilepsies (PME)** 

provoking factors (1989; Beghi et al., 2006).

**5.11 Lennox-Gastaut syndrome** 

report is an update and revision to the classification schemes which are now several decades old. It was devised to simplify the classification of seizures, as new concepts have emerged broadening our understanding of seizures and epilepsy syndromes. The 2010 ILAE report on revised terminology and concepts for organization of seizures and epilepsies is not a new classification of epilepsies but rather a reflection of new terminology and concepts that lead to a better understanding of the current neurobiology, clinical features, prognostic implications, and features relevant to clinical practice and research. The ILAE did not feel that there was adequate knowledge at this time to propose a new classification of seizures and the epilepsies. The following paragraphs are a summary of the ILAE's report on classification and terminology from 2010 (Berg et al., 2010).

#### **6.1 Generalized and focal redefined**

The new definition of generalized epileptic seizures is "originating at some point within, and rapidly engaging, bilaterally distributed networks" which include both cortical and subcortical structures, can appear localized but have inconsistent localization and lateralization, and can be asymmetric. Focal epileptic seizures originate "within networks limited to one hemisphere" and can originate in subcortical structures, can be localized or widely distributed, , and have a consistent site of ictal onset (Berg et al., 2010).

#### **6.2 Changes to the ILAE's 1981 classification of seizures**

There have been a few changes to the 1981 ILAE classification of seizures. First, neonatal seizures are no longer classified as a separate entity. Secondly, the subclassification of absence seizures was simplified to either typical, atypical, or absence with special features which now included myoclonic absence and eyelid myoclonia. Thirdly, epileptic spasms which were not previously acknowledged in the 1981 seizure classification are now included. It is still unknown whether epileptic spasms are focal in onset, generalized in onset, or both so they are classified as "unknown." Fourth, the distinction between simple partial and complex partial focal seizures was eliminated, however, the concept of impairment of consciousness/awareness is still recognized. Lastly, myoclonic astatic seizures are now termed "myoclonic atonic" seizures. (see Table 5).

#### **6.3 Focal seizures should be described**

Focal seizures should be described according to their specific elemental features and sequence of occurrence. The glossary of ictal semiology (Blume, et al., 2001) should be consulted for clearly defined and recommended descriptors. For example, the term "dyscognitive" corresponds to the old term complex partial seizure. (see Table 6).

#### **6.4 Replacing idiopathic, symptomatic, and cryptogenic**

The term idiopathic is replaced by the term "genetic." The epilepsy must be a direct result of a known or presumed genetic defect and the seizures a core symptom of the disorder. An example would be Dravet syndrome due to a mutation in the SCN1A mutation. Classifying an epilepsy as genetic does not exclude the possibility that environmental factors may contribute to expression of the disease.

The term symptomatic is replaced by the term "structural/metabolic." To be classified in this category, the epilepsy has to be associated with a structural lesion or metabolic disease that has been shown in previous studies to substantially increase the risk of developing

The Classification of Seizures and Epilepsy Syndromes 85

Instead of using the terms "disease" or "syndrome" to classify the epilepsies, four distinct groupings were developed: electroclinical syndromes, constellations, structural/metabolic epilepsies, and epilepsies of unknown cause (previously termed cryptogenic). The electroclinical syndromes are defined as "a complex of clinical features, signs, and symptoms that together define a distinctive, recognizable clinical disorder." They are defined on the basis of age of onset, specific EEG findings, seizure types, and other features which combine to from a specific diagnosis. Constellations are groups of epilepsies defined by diagnostically meaningful specific lesions or other causes which often have treatment implications. Examples of constellations are: mesial temporal epilepsy with hippocampal sclerosis, gelastic seizures and hypothalamic hamartoma, epilepsy with hemiconvulsion and hemiplegia, and Rasmussen syndrome. Regarding epilepsies due to structural or metabolic causes, more emphasis should be given to the seizure etiology rather than localization because the structural or metabolic etiology lends to a better understanding of prognosis. Based on these new concepts, instead of defining an epilepsy as "symptomatic temporal lobe epilepsy" the new terminology would read "epilepsy with focal seizures secondary to

**Electroclinical syndromes and other epilepsies** 

**6.5 Disease-syndrome groupings** 

a cavernous angioma in the temporal lobe." (See Table 7).

**Electroclinical syndromes arranged by age at onset** 

Epilepsy of infancy with migrating focal seizures

Myoclonic encephalopathy in nonprogressive disorders

Epilepsy with myoclonic atonic (previously astatic) seizures

Epileptic Encephalopathy with continuous spike-and-wave during sleep (CSWS)

Autosomal-dominant nocturnal frontal lobe epilepsy Late onset childhood occipital epilepsy (Gastaut type)

Benign epilepsy with centrotemporal spikes

Benign familial neonatal epilepsy Early myoclonic encephalopathy

Myoclonic epilepsy in infancy Benign infantile epilepsy

Benign familial infantile epilepsy

Epilepsy with myoclonic absences

Lennox-Gastaut syndrome

Landau-Kleffner syndrome Childhood absence epilepsy

Juvenile absence epilepsy

Adolescence-Adult

Ohtahara syndrome

West syndrome

Dravet syndrome

Febrile seizures plus Panayiotopoulos syndrome

Neonatal period

Infancy

Childhood

epilepsy. Examples of structural lesions include stroke, trauma, infection, tuberous sclerosis, and malformations of cortical development.

The term cryptogenic is replaced by the term "unknown cause." The epilepsies of unknown cause constitute over one-third of all epilepsies. These epilepsies are an area of active current research in the fields of genetics, immunology, and neuroimaging.


Table 5. The Classification of Seizures, from Berg, A.T., Berkovic, S.F, et. al. (2010). Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. *Epilepsia*, Vol. 51, No. 4, (April 2010), pp. 676-685, ISSN 1528-1167


Table 6. Replacement of the terms simple partial, complex partial, and secondarily generalized seizures, from Berg, A.T., Berkovic, S.F, et. al. (2010). Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. *Epilepsia*, Vol. 51, No. 4, (April 2010), pp. 676-685, ISSN 1528-1167

#### **6.5 Disease-syndrome groupings**

84 Novel Aspects on Epilepsy

epilepsy. Examples of structural lesions include stroke, trauma, infection, tuberous

The term cryptogenic is replaced by the term "unknown cause." The epilepsies of unknown cause constitute over one-third of all epilepsies. These epilepsies are an area of active

**Classification of Seizures** 

Table 5. The Classification of Seizures, from Berg, A.T., Berkovic, S.F, et. al. (2010). Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. *Epilepsia*, Vol. 51, No. 4, (April

With observable motor or autonomic components Simple partial seizure

With impairment of consciousness or awareness Complex partial seizure Evolving to a bilateral, convulsive seizure Secondarily generalized

Table 6. Replacement of the terms simple partial, complex partial, and secondarily generalized seizures, from Berg, A.T., Berkovic, S.F, et. al. (2010). Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. *Epilepsia*, Vol. 51, No. 4, (April 2010), pp. 676-685,

Involving subjective sensory or psychic phenomena only Aura

Replaces the term

seizure

current research in the fields of genetics, immunology, and neuroimaging.

Absence with special features Myoclonic absence Eyelid myoclonia

sclerosis, and malformations of cortical development.

Generalized seizures Tonic-clonic Absence

> Typical Atypical

Myoclonic

Clonic Tonic Atonic Focal seizures Unknown

2010), pp. 676-685, ISSN 1528-1167

impairment during seizure

ISSN 1528-1167

Myoclonic Myoclonic atonic Myoclonic tonic

Epileptic spasms

Descriptors of focal seizures according to degree of

Without impairment of consciousness or awareness

Instead of using the terms "disease" or "syndrome" to classify the epilepsies, four distinct groupings were developed: electroclinical syndromes, constellations, structural/metabolic epilepsies, and epilepsies of unknown cause (previously termed cryptogenic). The electroclinical syndromes are defined as "a complex of clinical features, signs, and symptoms that together define a distinctive, recognizable clinical disorder." They are defined on the basis of age of onset, specific EEG findings, seizure types, and other features which combine to from a specific diagnosis. Constellations are groups of epilepsies defined by diagnostically meaningful specific lesions or other causes which often have treatment implications. Examples of constellations are: mesial temporal epilepsy with hippocampal sclerosis, gelastic seizures and hypothalamic hamartoma, epilepsy with hemiconvulsion and hemiplegia, and Rasmussen syndrome. Regarding epilepsies due to structural or metabolic causes, more emphasis should be given to the seizure etiology rather than localization because the structural or metabolic etiology lends to a better understanding of prognosis. Based on these new concepts, instead of defining an epilepsy as "symptomatic temporal lobe epilepsy" the new terminology would read "epilepsy with focal seizures secondary to a cavernous angioma in the temporal lobe." (See Table 7).


The Classification of Seizures and Epilepsy Syndromes 87

The current ILAE Classification System for seizures and the epilepsies has formed the basis for a worldwide standardized approach to diagnosing, treating, and studying seizure disorders. The seizure classification system is primarily based on clinical semiology and EEG correlation, with a major distinction made between focal and generalized seizures. Focal seizures are further subdivided into simple and complex partial seizures, with the presence or absence of impairment of consciousness distinguishing the two. Generalized seizures are divided into absence, tonic, tonic-clonic, myoclonic, or atonic seizures. The epilepsy classification system highlights specific syndromes defined from anatomicpathological bases (mesial temporal lobe epilepsy with hippocampal sclerosis) to electroclinical bases (Lennox-Gastaut Syndrome). This system has been useful for both clinicians and researchers over the past 30 years, but new data from modern neuroimaging techniques, molecular biology studies, and genetics research has revealed the limitations of the 1981 and 1989 Classification systems. The 2010 ILAE report sets forth new concepts and terminology, with an emphasis on reducing the dichotomy between focal and generalized epilepsies. The 2010 ILAE report did not propose a new classification system, but noted its recommendations will likely be a precursor to a substantive revision of the current

Arzimanoglou, A., French, J., et al. (2009). Lennox-Gastaut syndrome: a consensus approach

Bancaud, J., & Talairach, J. (1992). Clinical semiology of frontal lobe seizures. *Adv Neurol,* Vol.

Beghi, M., Beghi, E., et al. (2006). Idiopathic generalized epilepsies of adolescence. *Epilepsia,* 

Berg, A.T., Berkovic, S.F, et. al. (2010). Revised terminology and concepts for organization of

Blume, W.T., Luders, H.O., et al. (2001). Glossary of ictal semiology. *Epilepsia*, Vol.42, No. 9,

Chee, M. W., Kotagal, P., et al. (1993). Lateralizing signs in intractable partial epilepsy:

Engel, J., Jr. (2001). A proposed diagnostic scheme for people with epileptic seizures and with

Engel, J., Jr. (2006). Report of the ILAE classification core group. *Epilepsia,* Vol.47, No.9,

French, J. A., Williamson, P.D., et al. (1993). Characteristics of medial temporal lobe epilepsy:

Hirose, S., Mitsudome, A., et al. (2005). Genetics of idiopathic epilepsies. *Epilepsia*, Vol. 46,

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(September 2001), pp. 1212-1218, ISSN 1528-1167

*Vol.* 42, No.6, (June 2001), pp. 796-803, ISSN 1528-1167

(September 2006), pp. 1558-68, ISSN 1528-1167

Suppl. 1, (March 2005), pp. 38-43, ISSN 1528-1167

1993), pp. 774-80, ISSN 1531-8249

57, n.d., pp. 3-58, ISSN 0091-3952

on diagnosis, assessment, management, and trial methodology. *Lancet Neurol* , Vol. 8**,** 

seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. *Epilepsia*, Vol. 51, No. 4, (April 2010), pp. 676-685, ISSN

blinded multiple-observer analysis. *Neurology*, Vol. 43, No.12, (December 1993), pp.

epilepsy: report of the ILAE Task Force on Classification and Terminology. *Epilepsia,* 

I. Results of history and physical examination. *Ann Neurol*, Vol.34, No.6, (December

**7. Conclusion** 

**8. References**

1528-1167

2519-25, ISSN 0028-3078

classification system in the near future.


Table 7. Electroclinical syndromes and other epilepsies, adapted from Berg, A.T., Berkovic, S.F, et. al. (2010). Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. *Epilepsia*, Vol. 51, No. 4, (April 2010), pp. 676-685, ISSN 1528-1167

#### **6.6 Pros and cons of the new ILAE classification (2010)**

The new classification of seizures and epilepsy syndromes is both an update of the old and a radical restructuring of it. It is a work in progress and it remains to be seen whether this new classification will come to acceptance or require further revision. The older classifications were simplified and specific seizure types were added. The replacement of the term "idiopathic" by the term "genetic" may be problematic. First, genetic etiologies due to a single gene mutations are still rare. Secondly, many of the epilepsies may be defined by multiple gene mutations and not due to a specific genetic defect. Additionally, some of the epilepsies don't fit into a single category in the new classification system. An example would be the age-specific epilepsies, such as the primarily generalized epilepsies. Overall however, the changes to the classifications needed to be made. Although it may be difficult to come to a consensus and there will be disagreement in the future, revisiting the way we classify seizures and epilepsy is a step forward for the field. (Shinnar, 2010).

#### **7. Conclusion**

86 Novel Aspects on Epilepsy

Juvenile myoclonic epilepsy

Less specific age relationship

Reflex epilepsies **Distinctive constellations** 

Rasmussen syndrome

**Epilepsies of unknown cause** 

Benign neonatal seizures

Tumor Infection Trauma Angioma Perinatal insults

Stroke Etc.

**epilepsy per se** 

Febrile seizures

Progressive myoclonus epilepsies

Other familial temporal lobe epilepsies

Familial focal epilepsy with variable foci

Hemiconvulsion-hemiplegia-epilepsy

Malformations of cortical development

Epilepsy with generalized tonic-clonic seizures alone

Autosomal dominant epilepsy with auditory features

Mesial temporal lobe epilepsy with hippocampal sclerosis

Gelastic seizures with hypothalamic hamartoma

*Epilepsia*, Vol. 51, No. 4, (April 2010), pp. 676-685, ISSN 1528-1167

classify seizures and epilepsy is a step forward for the field. (Shinnar, 2010).

**6.6 Pros and cons of the new ILAE classification (2010)** 

**Epilepsies attributed to and organized by structural-metabolic causes** 

Neurocutaneous syndromes (tuberous sclerosis complex, Sturge-Weber, etc.)

**Conditions with epileptic seizures that are traditionally not diagnosed as a form of** 

Table 7. Electroclinical syndromes and other epilepsies, adapted from Berg, A.T., Berkovic, S.F, et. al. (2010). Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009.

The new classification of seizures and epilepsy syndromes is both an update of the old and a radical restructuring of it. It is a work in progress and it remains to be seen whether this new classification will come to acceptance or require further revision. The older classifications were simplified and specific seizure types were added. The replacement of the term "idiopathic" by the term "genetic" may be problematic. First, genetic etiologies due to a single gene mutations are still rare. Secondly, many of the epilepsies may be defined by multiple gene mutations and not due to a specific genetic defect. Additionally, some of the epilepsies don't fit into a single category in the new classification system. An example would be the age-specific epilepsies, such as the primarily generalized epilepsies. Overall however, the changes to the classifications needed to be made. Although it may be difficult to come to a consensus and there will be disagreement in the future, revisiting the way we The current ILAE Classification System for seizures and the epilepsies has formed the basis for a worldwide standardized approach to diagnosing, treating, and studying seizure disorders. The seizure classification system is primarily based on clinical semiology and EEG correlation, with a major distinction made between focal and generalized seizures. Focal seizures are further subdivided into simple and complex partial seizures, with the presence or absence of impairment of consciousness distinguishing the two. Generalized seizures are divided into absence, tonic, tonic-clonic, myoclonic, or atonic seizures. The epilepsy classification system highlights specific syndromes defined from anatomicpathological bases (mesial temporal lobe epilepsy with hippocampal sclerosis) to electroclinical bases (Lennox-Gastaut Syndrome). This system has been useful for both clinicians and researchers over the past 30 years, but new data from modern neuroimaging techniques, molecular biology studies, and genetics research has revealed the limitations of the 1981 and 1989 Classification systems. The 2010 ILAE report sets forth new concepts and terminology, with an emphasis on reducing the dichotomy between focal and generalized epilepsies. The 2010 ILAE report did not propose a new classification system, but noted its recommendations will likely be a precursor to a substantive revision of the current classification system in the near future.

#### **8. References**


**6** 

S.E. Lehnart

*1Germany 2U.S.A.* 

*1Heart Research Center Göttingen, Dept. of Cardiology & Pulmonology, University Medical Center Göttingen,* 

*University of Maryland Baltimore,* 

*2Center for Biomedical Engineering and Technology,* 

**Combined Neuro-Cardiogenic Epilepsy** 

**Syndromes and Novel Mechanistic Insights** 

A large portion of patients with epilepsy without other obvious organ disease die unexpectedly. Epidemiological studies have estimated the rate of unexpected death in patients with epilepsy up to 24 times higher as compared to the general population (Ficker et al., 1998). However, in contrast to a significantly increased risk of sudden death in epilepsy patients, the underlying causes and pathophysiological mechanisms leading to sudden death are not well understood. This important problem is clinically identified as sudden unexplained death in epilepsy (SUDEP). Of note, SUDEP does not include death after prolonged seizures (e.g. status epilepticus) or due to other organ disease which excludes common cardio-pulmonary pathology. SUDEP occurs frequently in patients with idiopathic epilepsy with an estimated prevalence of 2% to 18% (Nashef et al., 2007; Tomson et al., 2008). It has been hypothesized that SUDEP and certain types of seizures may initiate a pathological signal to the heart, which subsequently triggers cardiac dysrhythmias and sudden death in epilepsy (Jehi & Najm, 2008; Surges et al., 2009). Alternatively, dysfunction of fast ion transport mechanisms, which directly control membrane excitability within the context of either the brain or the heart, may directly cause both neuronal or cardiac dysrhythmias. Importantly, if certain genetic defects in ion channel genes coexisted in the brain and heart, this may constitute a candidate mechanism of SUDEP and potentially precipitate life-threatening cardiac dysrhythmias (Nashef et al., 2007). Indeed, recent work has identified ion channelopathies in the context of generalized epilepsy that coexist in the brain and the heart. For the first time, defined molecular mechanisms of coexisting brain and heart dysrhythmias have been shown in genetically engineered rodent models with patient mutations which reproduce both neuronal and cardiac patient phenotypes. This article focuses on previous perspectives and recent insights about molecular epilepsy mechanisms, which underlie both dangerous dysrhythmias in the brain and heart. In addition, novel targeted treatment rationales based on molecular and cellular mechanisms

**1. Introduction** 

of dysrhythmias are discussed.

