Epilepsies

Focal Aware Seizures (Simple Partial Seizures)

FAS are seizures in which awareness is not altered at any point in the course of the seizure. FAS of purely subjective nature are often referred to as auras or isolated auras . The manifestations of FAS depend on the brain region involved in the ictal discharge. However, it is important to recognize that the seizure activity may originate in silent areas, and the first clinical manifestations may reflect seizure spread to other brain regions. Nevertheless, FAS and auras may have important lateralizing and localizing value. For example, focal clonic or tonic activity is usually contralateral to the hemisphere involved in seizure activity. Somatosensory auras, visual auras, and auditory auras are often useful in suggesting localization and lateralization of the epileptogenic zone. However, some auras are nonspecific and may be seen with a variety of localizations.

Auras are typically short in duration, lasting seconds to minutes. Some patients may experience a prodrome , a difficult-to-describe feeling that a seizure may occur. Prodromes may last hours or even days and have to be distinguished from auras. On the other hand, auras may occasionally be prolonged, in which case they are called aura continua , which is a form of focal nonconvulsive status epilepticus without impairment of consciousness.

Focal Impaired Awareness Seizures (Complex Partial Seizures)

FIAS are characterized by altered awareness during the seizure. Impairment may be very subtle, manifesting with slight confusion, fuzziness, or slowing of responses. A patient may have some recollection of events or total amnesia for the event. FIAS may start with an aura or may start with loss of awareness. It is sometimes difficult to determine if awareness was impaired. The patient may be totally conscious but unable to respond verbally because of aphasia or unable to respond or react because of motor inhibition.

Impaired awareness seizures may arise from any lobe but most commonly arise from the temporal lobe; the frontal lobe is the second most common site of seizure origin. The most common type of motor activity in this seizure type is automatism, described earlier. The different seizure manifestations in seizures arising from different lobes of the brain are discussed in the next section.

Focal to Bilateral Tonic-Clonic Seizures (Partial Seizures Evolving to Generalized Tonic-Clonic Activity)

These seizures may start as focal aware or FIAS. The transition to bilateral tonic-clonic activity usually involves versive head turning in a direction contralateral to the hemisphere of seizure onset (see Fig. 100.1 ), and focal or lateralized tonic or clonic motor activity. The pattern of evolution may be clonic-tonic-clonic in some instances. The bilateral tonic phase may be asymmetrical, with flexion on one side and extension on the other. This has been called figure-of-four posturing ( ; Fig. 100.4 ). Some asymmetry and asynchrony may also occur in the clonic phase, resulting in a slight degree of side-to-side head jerking ( ). The evolution from tonic to clonic activity is gradual and not always simultaneous in all affected body parts. A phase of high-frequency tremor has been referred to as the tremulous or vibratory phase of the seizure ( ). Clonic activity typically decreases in frequency over time, with longer intervals between jerks toward the termination of the seizure. The clonic activity may end on one side of the body first so that clonic activity may then appear lateralized to one side. In addition, there may be a late head turn ipsilateral to the hemisphere of seizure origin ( ). After the motor activity stops, the individual is usually limp and has a loud snoring respiration often referred to as stertorous respiration ( Video 100.5 ). During the course of recovery, there may be variable agitation. The speed of recovery is expected to be slower with longer and more severe seizures.

Video 100.5 Focal to bilateral tonic-clonic seizure in a patient with left temporal seizure origin.

Focal Seizure Semiology in Relation to Localization

Focal Seizures Originating in the Insular Cortex

Insular epilepsy is uncommon and frequently unrecognized because of the inability to record directly from the insula with scalp electrodes. Subjective symptoms that should suggest seizure origin in the insula include laryngeal discomfort, possibly preceded or followed by a sensation in the chest or abdomen, shortness of breath, and paresthesias around the mouth or also involving other contralateral body parts ( ). Objective seizure manifestations include dysarthria/dysphonia, sometimes evolving to complete muteness. With seizure progression in some patients, tonic spasm of the face and upper limb, head and eye rotation, and at times generalized dystonia occur ( ). Hypersalivation is also very common and can be impressive. Insular-onset seizures may spread to other brain regions and can be disguised as temporal lobe, parietal lobe, or frontal lobe epilepsy ( ; ; ).

Generalized Absence Seizures

Typical absence seizures are characterized by a sudden blank stare with motor arrest, usually lasting less than 15 seconds ( ). The individual is usually unresponsive and unaware. The seizure ends as abruptly as it starts, and the patient returns immediately to a baseline level of function with no postictal confusion but may have missed conversation and seems confused as a result ( Video 100.7 ). If the only manifestation is altered responsiveness and awareness, with no associated motor component, the absence seizure is classified as simple absence . Most often, generalized absence seizures include mild motor components and are classified as complex absence . The most common motor components are automatisms such as licking the lips or playing with an object that was held in the hand before the seizure. Other motor components include clonic, tonic, atonic, and autonomic manifestations. Clonic activity may affect the eyelids or the mouth. An atonic component may manifest with dropping an object or slight head drop or drooping of the shoulders or trunk. Tonic components may manifest with slight increase in tone.

Video 100.7 Generalized absence seizure with immediate return of responsiveness postictally.

The EEG hallmark of a typical generalized absence seizure is generalized 2.5- to 4-Hz spike-and-wave activity with a normal interictal background ( Fig. 100.5 ). Atypical absence seizures are diagnosed primarily based on a slower (<2.5 Hz) frequency of the EEG spike-and-wave activity. Less important distinctions are that the onset and termination of an atypical absence seizure may be less abrupt and the motor components a bit more pronounced than seen with typical absence seizures. Atypical absence seizures usually occur in individuals with impaired cognitive function. Affected individuals usually have associated seizure types such as generalized tonic, generalized atonic, and GTC seizures.

Additional generalized absence seizure types recently recognized by the ILAE include myoclonic absences . The key manifestation of these seizures is a prominent rhythmic myoclonus predominantly affecting the limbs ( ). Otherwise, myoclonic absences resemble typical absence seizures with respect to impairment of consciousness. Another related seizure type recently recognized is eyelid myoclonia with absence . The eyelid myoclonia consists of pronounced rhythmic jerking of the eyelids, usually associated with an upward deviation of the eyes and retropulsion of the head ( ). There may or may not be associated generalized spike-and-wave activity on EEG. Absence seizures may evolve to GTC activity ( ; Video 100.8 ).

Video 100.8 Generalized absence seizure evolving to bilateral tonic-clonic seizure.

Generalized Myoclonic Seizures

Myoclonic seizures are muscle contractions lasting a fraction of a second (<250 ms), in association with an ictal EEG discharge ( ). The myoclonic jerk can be generalized, affecting the whole body, or could affect just the upper extremities or (rarely) the head or trunk, or even the diaphragm. The myoclonic jerks may affect one side of the body at one time, but typically the other side is affected at other times. The jerks can be single or could occur in an arrhythmic cluster ( Video 100.9 ). It should be noted that myoclonus is not always epileptic ( ). Myoclonus can be generated anywhere along the central nervous system (CNS). Epileptic myoclonus is generated in the cerebral cortex and is usually associated with a single or brief serial spike-and-wave or polyspike-and-wave activity.

Video 100.9 Myoclonic seizures in a patient with juvenile myoclonic epilepsy.

Negative myoclonic seizures consist of a very brief pause in muscle activity rather than a brief muscle contraction ( ). Just as with positive myoclonus, negative myoclonus can be generalized, bilateral with limited distribution, or even focal, typically with shifting lateralization.

Generalized myoclonic seizures may be immediately followed by a loss of tone. The seizure type is called myoclonicatonic . Historically it was called myoclonicastatic . The seizures are brief (1 second or less) but may be associated with falls and injuries ( Video 100.10 ). The EEG shows generalized spike-and-wave or polyspike-and-wave discharge. The slow wave is prolonged and associated with the electromyographic (EMG) silence characteristic of the atonic phase. Myoclonic seizures may precede a more sustained tonic contraction, and the resultant seizures may be referred to as myoclonic-tonic seizures ( ). Generalized myoclonic seizures may cluster just before a GTC seizure occurrence ( Video 100.11 ).

Video 100.10 Myoclonic atonic seizure.

Video 100.11 Cluster of myoclonic seizures leading to tonic-clonic seizure.

Generalized Clonic Seizures

Unlike myoclonic seizures, which are single jerks (but may occur in arrhythmic clusters), each generalized clonic seizure consists of a series of rhythmic jerks. Generalized clonic seizures are uncommon and particularly rare in adults ( ). They are more frequently seen in certain epileptic syndromes of infancy and childhood. For example, clonic seizures are a common seizure type of severe myoclonic epilepsy of infancy (Dravet syndrome). Clonic seizures are also noted in progressive myoclonic epilepsies.

Generalized Tonic Seizures

Generalized tonic seizures are typically brief seizures, lasting a few seconds to 1 minute ( Video 100.12 ). Their onset may be gradual or abrupt. They may be initiated with a myoclonic jerk. They can vary in severity from subtle, with slight increase in neck tone with upward deviation of the eyes, to massive, with involvement of the axial muscles and extremities. Proximal muscles are the most affected. Most commonly there is neck and trunk flexion as well as abduction of the shoulders and flexion of the hips. However, extension may also occur. Tonic seizures may be asymmetrical, which could result in turning to one side. The pattern of muscle involvement may change over time so that there may be a change in the position of the limbs over the course of the seizure. Autonomic changes may occur, with tachycardia, pupil dilation, and flushing. Involvement of respiratory muscles could cause apnea and cyanosis. The tonic contraction may end with one or more pauses that result in a few clonic jerks. A postictal state with confusion may occur, but recovery is usually rapid. However, tonic seizures may be followed by atypical absence, resulting in what appears to be a more prolonged postictal state. This has been referred to as tonic-absence seizure ( ). Generalized tonic seizures occur most often out of sleep and drowsiness.

Video 100.12 Brief tonic seizure.

Epileptic Spasms

Epileptic spasms have similarities to generalized tonic seizures but a shorter duration that is intermediate between generalized myoclonic and generalized tonic seizures ( ), with a typical duration of 0.5–2 seconds. The pattern of contraction is “diamond-shaped,” with intensity of contraction maximal in the middle of the spasm and less at the beginning and end. Epileptic spasms were also called infantile spasms and salaam attacks . Because their occurrence is not restricted to infants, the preferred current term is epileptic spasms. The classic epileptic spasm involves neck and trunk flexion and arm abduction with a jackknife pattern, but extension may be seen. Epileptic spasms typically occur in clusters recurring every 5–40 seconds. In a cluster, the initial spasms may be subtle or mild, increase in intensity as the cluster progresses, and decrease in intensity again toward the end of the cluster ( ).

Generalized Tonic-Clonic Seizures

GTC seizures are dramatic and the best recognized form of seizures. They are commonly referred to as grand mal , but this term is archaic and does not distinguish seizures of focal onset from those with a generalized onset. GTC seizures do not have an aura, but they may be preceded by a prodrome—the vague sense a seizure will occur—lasting up to hours. Seizure onset is abrupt, most often with loss of consciousness and a generalized tonic contraction, but some seizures may be initiated with a series of myoclonic jerks, leading to the term myoclonic-tonic-clonic seizure (see Video 100.11 ) . The tonic phase may have asymmetrical movements, and these often change from seizure to seizure. One such commonly encountered asymmetry is versive head turning, which is not evidence of a focal onset ( ; ). The tonic phase includes an upward eye deviation with eyes half open and the mouth open. Involvement of the respiratory muscles usually produces a forced expiration that produces a loud guttural vocalization, often referred to as the epileptic cry. Cyanosis may occur during the tonic phase in association with apnea. The tonic phase gradually evolves to clonic activity. The transition can be with initially high-frequency and low-amplitude motion, often referred to as a vibratory phase . With seizure progression, the frequency of clonic jerks decreases, and the amplitude may initially increase but later decreases just before the seizure stops. In the immediate postictal state the individual is limp and unresponsive. Respiration is loud and snoring in character (stertorous) . The postictal state is often followed by sleep, although the individual may awaken briefly with postictal confusion. Tongue biting commonly occurs and most often affects the side of the tongue. Incontinence of urine is common, and incontinence of stool may also occur. After awakening, patients often have a pronounced headache and generalized muscle soreness. GTC seizures rarely last more than 2 minutes. The severity may vary. The postictal state seems to correlate with severity and duration.

Generalized Atonic Seizures

Generalized atonic seizures are associated with very brief, sudden loss of tone and vary from extremely subtle, manifesting with only a head drop, to generalized loss of tone and falling. Atonic seizures may result in falling if the person is standing, called a drop attack. However, drop attacks may be the result of both generalized atonic and generalized tonic seizures. There is a very brief loss of consciousness and brief postictal confusion. Seizures are usually very brief, lasting 1 second to a few seconds. They may be preceded by a brief myoclonic jerk, in which case the seizure type is called myoclonic-atonic (see Video 100.10 ). Very brief myoclonic-atonic seizures are typical of the syndrome of myoclonic-astatic epilepsy (Doose syndrome) ( ). More prolonged atonic seizures can be seen with Lennox-Gastaut syndrome or other symptomatic generalized epilepsies. Despite their brief duration, generalized atonic seizures can result in serious injury and are an important cause of morbidity in epilepsy.

Generalized-Onset Seizures with Focal Evolution

Generalized-onset seizures rarely may evolve to focal seizures ( ; ; ). This seems to occur with either myoclonic or absence seizures. The clinical manifestations most often are behavioral arrest and staring, with minor automatisms. However, focal motor manifestations may also occur. This type of seizure tends to be prolonged and may be associated with postictal confusion ( ; ).

Benign Familial Neonatal Epilepsy

Benign familial neonatal epilepsy was previously referred to as benign familial neonatal convulsions ( ). This rare, dominantly inherited disorder is due to mutations affecting voltage-gated potassium channel genes ( KCNQ2, KCNQ3 ) ( ). Affected infants are usually full term and appear normal at birth. In 80% of instances, seizures start on the second or third day of life, although some infants may develop seizures later in the first month of life. The seizures are typically clonic but often preceded by a tonic component. They are more often unilateral but can also be bilateral. The seizures remit within 2–6 months. There is a slight increase in the risk of later epilepsy (11%–15%).

Early Myoclonic Encephalopathy and Ohtahara Syndrome

Early myoclonic encephalopathy and Ohtahara syndrome have much in common, including age at onset in the neonatal period, severe seizure manifestations, and an EEG pattern of burstsuppression, in which periods of high-voltage EEG activity are separated by periods of generalized attenuation ( ; ; ).

Early myoclonic encephalopathy is characterized by focal myoclonus involving limbs or face that is very frequent, sometime continuous, shifting from one region to another. Generalized massive myoclonus may appear shortly thereafter, as will focal motor seizures. Epileptic spasms typically develop later in the course of the disorder. Neurological status is abnormal, either at birth or with the development of clinical seizures. Most infants are hypotonic. The prognosis is poor. There is increased mortality in the first few years of life, and survivors have considerable developmental delay.

Ohtahara syndrome is characterized by epileptic spasms as the predominant seizure type, but a third of affected infants also have other seizure types, including focal motor seizures, hemiconvulsions, and generalized motor seizures. The epileptic spasms are associated with generalized attenuation on EEG. The prognosis is also poor, with very high mortality in the first few years of life, and severe mental and physical handicap in survivors. The EEG may evolve from the initial suppression-burst pattern to a hypsarrhythmia pattern, typical of West syndrome.

West Syndrome

West syndrome has a later age at onset, with a peak onset between 3 and 7 months of age. It is characterized by a clinical triad of epileptic spasms, arrest or deterioration of psychomotor development, and a characteristic EEG pattern called hypsarrhythmia ( ). The disorder is heterogeneous in its etiology. Epileptic spasms are usually the initial manifestation. They tend to occur in clusters, sometimes multiple times a day. Approximately two-thirds of infants have brain lesions. Psychomotor development may be abnormal prior to onset, but there is a clear deterioration after onset. The spasms may have asymmetries, which are more likely when there is a focal brain lesion. The prognosis is variable, with a small proportion of patients recovering quickly without sequelae. This is more likely to happen in the absence of brain pathology. Otherwise, more than 70% develop intellectual disability and other cognitive disabilities. The treatment of infantile spasms has some important differences from treatment of other seizure types. Steroids such as corticotropin (adrenocorticotropic hormone [ACTH]) and prednisone are helpful, particularly in the absence of underlying known pathology.

Hypsarrhythmia is characterized by high-voltage disorganized EEG activity with slow waves and multifocal spikes and sharp waves punctuated by periods of generalized attenuation ( Fig. 100.7 ). When a spasm occurs, it is usually during a period of attenuation. The attenuation may have superimposed high-frequency, low-voltage EEG activity. The periods of attenuation are typically very short in duration, lasting 1–2 seconds.

Dravet Syndrome

Dravet syndrome, also called severe myoclonic epilepsy of infancy , is usually due to a de novo mutation affecting the SCN1A gene encoding the α ₁ sodium channel subunit ( ). De novo mutations account for about 95% of cases. It may also be due to a nonsense mutation of the GABRG2 γ-aminobutyric acid A (GABA _A ) receptor subunit ( ). Dravet syndrome and related epileptic or developmental encephalopathies may be caused by a number of other genetic mutations ( ). The typical clinical presentation is that a previously normally developing infant has febrile status epilepticus at around 6 months of age, and then recurrent generalized or shifting hemiclonic seizures are seen, often triggered by fever. After 1 year of age, other seizure types appear, including myoclonic seizures, absence seizures, and FIAS as well as atonic seizures at times. The seizures are drug resistant and may be exacerbated by some sodium channel blockers such as carbamazepine and lamotrigine. A delay or arrest in development may occur, and even regression may be seen, typically after episodes of prolonged seizure activity ( ; ). The prognosis is poor; the majority of individuals develop intellectual disability and at times ataxia and spasticity.

Borderline severe myoclonic epilepsy of infancy may include variations such as epilepsy with the absence of myoclonic seizures or even other seizure types.

It has now become recognized that Dravet syndrome accounts for a large proportion of individuals previously diagnosed with vaccine encephalopathy ( ). The fever associated with vaccination may cause an earlier age at onset of Dravet syndrome, but it does not affect the eventual course of the condition ( ).

Genetic Epilepsy with Febrile Seizures Plus

Genetic epilepsy with febrile seizures plus (GEFS+) appears to be autosomal dominant in inheritance, often due to a sodium channel mutation, most often in the SCN1A or SCN1B gene ( ; ). It can also be due to a mutation in the γ ₂ subunit of the GABA _A receptor ( ). No mutation has been identified in the majority of families. The condition has a heterogeneous phenotype in affected individuals, even within the same kindred ( ; ; Fig. 100.8 ). Some individuals have only the typical febrile seizure phenotype, with febrile seizures disappearing by 6 years of age. Other individuals have febrile seizures plus , which refers to febrile seizures persisting beyond 6 years of age or febrile seizures intermixed with afebrile GTC seizures. Other individuals even have other seizure types such as generalized absence or myoclonic seizures. Less common seizure types are myoclonic-atonic and focal seizures typical of temporal lobe origin ( ; ).

Panayiotopoulos Syndrome

The onset of seizures in Panayiotopoulos syndrome is typically between 1 and 14 years of age, with a peak at 4–5 years ( ). Seizures include autonomic manifestations, particularly ictal vomiting, altered responsiveness and arrest of activity, and deviation of the eyes to one side. Autonomic manifestations are particularly pronounced ( ). Seizures can be very prolonged, lasting longer than 30 minutes, qualifying for focal nonconvulsive status epilepticus. Seizures predominate during sleep. The EEG shows multifocal spikes but with posterior predominance. Despite the alarming seizure manifestations, prognosis is generally good. Seizures are infrequent, with about a quarter of patients having only one seizure and half having two to five at most. Remission typically occurs within 1–3 years of onset.

Epilepsy with Myoclonic-Atonic Seizures (Myoclonic-Astatic Epilepsy or Doose Syndrome)

This presumed genetic epilepsy is characterized by seizure onset between 18 and 60 months of age ( ). The characteristic seizure types are myoclonic and myoclonic-atonic seizures, present in all affected children. Tonic-clonic seizures are also seen in a majority of children. Atypical absence seizures are also common and frequently associated with reduced muscle tone. Pure atonic seizures may also occur. Generalized tonic seizures are less frequently seen. GTC seizures are most often the seizure type that results in the diagnosis of epilepsy, with smaller seizures noticed thereafter. Seizures can be easily precipitated by inappropriate treatment with carbamazepine. The course of the condition is somewhat unpredictable. In more than half of affected children, the seizures go into remission. More than half of patients also have normal cognitive function, with less than half having mild to severe intellectual disability. A worse prognosis is predicted by GTC seizures in the first 2 years of life and early status epilepticus ( ).

Self-Limited Epilepsy with Centrotemporal Spikes

Self-limited epilepsy with centrotemporal spikes, previously known as benign epilepsy with centrotemporal spikes (BECTS) is also referred to as benign rolandic epilepsy . This is the most common form of idiopathic focal epilepsy in children ( ). Seizures begin between 3 and 13 years of age, with a peak between 5 and 8 years. Affected children will have had a normal development and normal cognitive function. Seizures typically start with paresthesias affecting one side of the face, particularly around the mouth, then contraction of that side of the face evolving into clonic activity of the face. Increased salivation and drooling occurs. Consciousness is preserved in the vast majority of children if the seizure does not evolve to bilateral tonic-clonic activity. Seizures are typically nocturnal and generally have a low rate of recurrence, so treatment is not always necessary. The natural history is characterized by spontaneous remission around the time of puberty. Patients with BECTS may have cognitive and behavioral problems while the condition is active, but long-term prognosis is excellent ( ).

BECTS has long been thought to have a genetic basis, but the concordance in identical twins is low, suggesting that other mechanisms may play a role ( ). The diagnosis of BECTS depends on the clinical presentation as well as the EEG. The typical EEG abnormality is high-voltage central-midtemporal blunt sharp waves activated in sleep ( Fig. 100.9 ). These can become bilateral independent in deeper sleep. Atypical fields are common, particularly posterior temporal or parietal. The incidence of generalized spike-and-wave discharges in affected individuals is increased ( ; ).

Autosomal Dominant Nocturnal Frontal Lobe Epilepsy

Age at seizure onset in autosomal dominant nocturnal frontal lobe epilepsy is highly variable but is most often younger than age 20, with a mean between 8 and 11 years. Seizures typically arise out of sleep. In their most pronounced expression, they may be hypermotor with vigorous frenetic movements of the extremities such as thrashing, kicking, or bicycling. The seizures may be asymmetrical tonic, sometimes with evolving posturing, or may have a mixture of hypermotor and tonic manifestations. The seizures are usually stereotyped. They are typically short in duration, lasting less than 30 seconds. They can be so short as to simply manifest with paroxysmal arousal ( ). The condition is often misdiagnosed as a sleep disorder or psychogenic seizures ( ).

This disorder is genetically heterogeneous ( ) but typically due to mutations in the neuronal nicotinic acetylcholine receptor ( ). Carbamazepine appeared particularly effective in this condition. Interestingly, the mutated nicotinic receptors were found to be more sensitive to carbamazepine than to valproate ( ).

Late-Onset Childhood Occipital Epilepsy (Gastaut Type)

The age at onset of seizures in late-onset childhood occipital epilepsy ranges from 3 to 16 years, with a mean age of 8 ( ). The seizures are of occipital lobe onset and manifest with visual symptoms. The ictal phenomena include elementary visual hallucinations, complex visual hallucinations and illusions, visual loss in one field or total blindness, eye deviation, and eye blinking. There may be progression of seizure manifestations with spread beyond the occipital lobe, particularly lateralized or GTC activity. Consciousness is usually preserved if seizure activity does not spread beyond the occipital lobe. Postictal headache is a very common symptom, resulting in confusion with migraine. The interictal EEG is characterized by occipital spikes and sharp waves that can be extremely frequent, and typically activated with eye closure. The discharges can be so frequent as to raise concern for an ictal pattern.