EEG and semiologies in generalized epilepsies

Question 1

Classification generalized epilepsies

Answer 1

Based on seizure semiology, combined with EEG and appropriate personal and family history

Question 2

Generalized seizures

Answer 2

Tonic-clonic
Absence: typical, atypical, with special features (myoclonic absences, absence with eyelid myoclonic)
Myoclonic: myoclonic, myoclonic-atonic
Clonic
Tonic
Atonic

Question 3

Generalized tonic-clonic seizures are seen in:

Answer 3

In juvenile absence epilepsy, juvenile myoclonic epilepsy, epilepsy with generalized tonic–clonic seizures only, as well as in provoked seizures, including alcohol withdrawal seizures.

Question 4

GTC semiology

Answer 4

Duration of 1-2 minutes, patients have no recollection of the event

Prodrome: This is a state where some patients might feel a sense of uneasiness, irritability, or difficulty concentration and occur hours to a day before the actual seizure.

Tonic phase: Brief flexion spasm of axial and arm muscles is associated with the loss of consciousness. Involvement in respiratory muscles leads to vocalization (the ictal cry), and patients become apneic. During the initial closing of the jaw, tongue biting can happen, more commonly commonly on the side of the tongue or the inner cheek. Thenormal position of the tongue does not include protrusion for biting to affect the tip. Falls can occur if the patient is standing. The eyes move up and the pupils dilate. Autonomic signs consist of increase in heart rate and blood pressure, sweating, and tracheobronchial secretions. Foaming at the mouth can occur due to involvement of the glottic muscles and prolonged seizures can cause cyanosis.

Clonic phase: Starts as a tremor, progressing to 4Hz activity (which denotes the onset of the clonic phase, tremor is typically between 4 and 6 Hz) and slower. This phase involves cycles of inhibition interspersed by brief muscle activity. Each spasm is associated with pupillary contraction and dilation. Post-ictal state: Respiratory activity resumes with slower and deeper phases at times mimicking deep sleep with snoring. The muscles are relaxed, including the sphincters, which can lead to bowel or bladder incontinence. Variable degrees of confusion typically follow the period of stupor or sleep. Headache, generalized body, or muscle aches are also commonly reported. The entire postictal state can last minutes to hours and is proportional to the duration of the seizure and the age of the patient, lasting longer in children. Focal face or limb weakness (Todd’s paresis) is less common than in
secondary generalized seizures. Trauma from falls on hard objects, tongue biting, vertebral compression fractures, aspiration pneumonia, and neurogenic pulmonary edema can occur. The last complication in addition to central apnea and cardiac arrest can play a role in sudden unexplained death in epilepsy or SUDEP

Question 5

GTC interictal

Answer 5

Interictally waking EEG is often normal and the yield of interictal epileptiform discharges is increased by hyperventilation and sleep. Photosensitivity (photic-stimulus-
induced generalized epileptiform discharges) can be seen in up to 25% of cases where there is also a family history of epilepsy.

Epileptiform discharges, when present, are generalized, high-voltage rhythmic spike-and-wave activity, anteriorly predominant and sometimes can only be seen anteriorly. In children, however, there can be posterior predominance. Subtle asymmetry in the generalized discharges is commonly noted. In NREM sleep, briefer, slower, and fragmented discharges can be seen.

Nonepileptiform activities such as generalized excessive low-voltage beta-activity or mild-generalized slow activity can be seen secondary
to antiseizure medications. Chronic therapy with valproate and benzodiazepines can abolish epileptiform discharges. Frontal intermittent rhythmic delta activity (FIRDA) has also been reported.

Question 6

GTC ictal

Answer 6

If generalized tonic–clonic seizures are preceded by absence (3Hz spike-and-slow-wave) or myoclonic jerks (theta-range spikes or polyspikes and slow waves), then corresponding EEG ictal rhythms can be seen.

The tonic phase onset is predominated by muscle artifact obscuring the EEG. If neuromuscular blockers are used, the EEG shows higher amplitude and decreasing frequency discharge in the range of 9–10Hz called the “epileptic recruiting rhythm.” Small side-to-side delay can be noted with computer analysis, but this delay is inconsistent. Slower mixed frequency discharges with increasing amplitude rhythmic spikes are seen bilaterally followed by repetitive complexes of high-amplitude spike-and-slow-wave activity in association with the tremor. Slowing of repetitions occurs with the start of violent jerks of the clonic phase, as cortical inhibition progresses. During the postictal state, an isoelectric EEG followed by diffuse slow activity can be seen, which corresponds to neuronal hyperpolarization. Focal abnormalities during postictal states are not expected and might suggest focal epilepsy with secondary generalization.

Question 7

Typical absence summary

Answer 7

This is the hallmark of the childhood absence epilepsy (CAE). Girls are affected more often than boys and present between 4 and 8 years of age with very frequent staring episodes (up to hundreds per day). Prognosis is excellent with treatment, and hence, a low threshold should be maintained to obtain EEG for diagnosis.

Question 8

Typical absence EEG

Answer 8

EEG record is ideally obtained between 8 and 10 am when the event frequency can be maximal.

“Interictal” and Ictal EEG—The interictal nature of these discharges is debatable. Detailed neuropsychological testing conducted in patients with the absence showed deficits even when discharges were shorter than 3s. In 30% of cases, a rhythmic slow posterior activity or occipital intermittent rhythmic delta activity (OIRDA) can be seen. Generalized bilaterally synchronous high-voltage 2.5–3.5Hz rhythmic spike-and-wave discharges with bifrontal predominance are classically seen during absence seizures. The initial negative deflection is of lower voltage compared to the after-wave, which is of very higher amplitude. At the onset the discharge can be of higher frequency ~3.5Hz and slows down over time. Occasionally, generalized polyspike-and-wave discharges, even bilateral independent focal frontal spikes, can occur in typical absence. These discharge trains often last 5–15s but can last up to 30s. Hyperventilation often precipitates longer trains of discharges.

During non-REM sleep, single or multiple spike-and-wave discharges are frequent.

Question 9

Typical absence semiology

Answer 9

Staring episodes associated with cognitive impairment and change in facial expression lasting for approximately 10s. Rhythmic lid or eye clonic–tonic activity, ocular retropulsive movements that might extend to involve head or trunk, and sometimes oral automatisms can be seen. If the events last longer, there can be nonoral gestural motor automatisms. Temporal semiological analysis in relation to the EEG discharge can show variability in the same patient. Posture is usually maintained and falls are not often reported despite frequent episodes. The patients themselves are not aware of having these episodes. A child who has an event in the middle of a sentence will continue the sentence exactly where it was left off, while observers can appreciate the pause. In the physician’s office, hyperventilation (in children, performed by blowing on a pinwheel) can elicit a seizure in approximately 90% of patients with childhood absence epilepsy.

Question 10

JAE

Answer 10

JAE has a typical age of onset between 9 and 13years. Absence seizures typically occur in clusters upon awakening, and ocular retropulsive movements are less often seen. Seizures are less frequent than in CAE. EEG during absences shows generalized high-voltage spike-and-wave discharge, which may be slightly faster (3–4Hz) than in CAE. About 80% of patients also have generalized tonic–clonic and myoclonic seizures.

Question 11

Atypical absence

Answer 11

Summary: This is an important seizure type in patients with Lennox–Gastaut syndrome. Seizures occur lifelong and are more resistant to treatment, and photosensitivity is not a feature.

Semiology: Onset and end of seizures is more gradual and eyelid myoclonus is not rhythmic. Forward head movement, perioral myoclonus, and drooling are notable. The seizure is usually less than 10s in duration and the child can continue simple activities during an event.

EEG in atypical absence: The ictal EEG shows 2–2.5Hz slow spike-and-wave discharge, which can be irregular. Interictal EEG shows an abnormal background with diffuse slowing and multifocal interictal spikes.

Question 12

Myoclonic absence (absence with special features)

Answer 12

Summary: The mean age of onset is seven years with boys more often affected than girls. Cognition and development are abnormal

in two-thirds of patients who can have other seizure types such as generalized tonic–clonic seizures. These seizures are very frequent, can occur in sleep, and tend to be resistant to therapy.

Semiology: Events can be precipitated by hyperventilation or upon awakening. Consciousness is impaired to a variable extent. Eyelid movements are rare, but perioral myoclonia is frequent. The arms tend to stay high due to coexistent tonic contraction, and rhythmic jerks are typically clonic (rather than myoclonic) in nature and involve the arms more commonly than the legs. Rarely, the clonic activity can be unilateral. Events can last for 10–60s. Falls from seizures are uncommon, and postictal state is not seen. Respiratory arrest and urinary incontinence can occur.

EEG in myoclonic absence: Ictal EEG consists of generalized rhythmic 3Hz spike-and-wave discharges coinciding with the rhythmic jerking of arms and can last 10–60s. Occasionally, the classic discharges are intermixed with polyspike-and-wave discharges.

Question 13

In what syndromes/conditions/circumstances are myoclonic seizures seen?

Answer 13

Myoclonic seizures are seen in many epilepsy syndromes, including juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and progressive myoclonic epilepsies, among others.

Question 14

Myoclonic seizures semiology

Answer 14

Semiology: Brief, symmetric, bilaterally synchronous jerks affect mainly the shoulders and arms occurring singly or in clusters. Jerks tend to cluster upon awakening, more often in morning, and sometimes during nocturnal awakenings or when tired in the evenings. At times, ideation of the jerks can induce myoclonic jerks. Patients remember these jerks and are sometimes only perceived internally as “mild electrical shock.”

Objects in the hands tend to be thrown off and falls can occur with leg muscle involvement while standing.

Question 15

Myoclonic seizures EEG

Answer 15

6.12): The background is typically normal. Interictal epileptiform and ictal discharges consist of generalized high-voltage polyspike-and-wave or spike-and-wave discharges that are bilaterally symmetric with bifrontocentral predominance. They can be induced by photic stimulation. In sleep, fragments of these discharges with shifting right-left predominance can be seen. Limb electrodes can demonstrate the myogenic activity that is time locked with EEG discharges.

Question 16

Myoclonic–atonic seizures

Answer 16

These are the main seizure type in myoclonic-astatic epilepsy of early childhood—Doose syndrome.

Semiology: Falls preceded by variable jerky movement of the face/trunk/arms. EEG: Interictally, generalized slow spike-and-wave discharges are seen. Parietal theta or occipital delta activity can be seen as well. Ictal discharges consist of generalized slow spike-and-wave or polyspike-and-wave discharges of 2–3Hz. The spike component corresponds to the myoclonic jerk, and slow wave corresponds to atonia. The EEG can help differentiate from negative myoclonus seen in frontal lobe epilepsy with rapid bilateral synchrony. Negative myoclonus interrupts the tonic activity and is <500ms in duration without the evidence of antecedent myoclonia causing the drops.

Question 17

In what syndromes/conditions/circumstances are clonic seizures seen?

Answer 17

Generalized clonic seizures can be seen in Angelman’s syndrome, progressive myoclonic epilepsies, and epilepsy with myoclonic-astatic seizures (also known as Doose syndrome). The generalized clonic or myoclonic activity can also be seen during a syncopal episode.

Question 18

Clonic seizures semiology

Answer 18

Semiology: Clonic seizures are predominantly seen in infants and children. They can be lateralized at first and then generalize or vice versa. Sometimes, the tonic phase is short and a tonic–clonic seizure appears like generalized clonic seizure. Autonomic changes are seen in prolonged seizures consisting of retention of bronchial secretions leading to respiratory distress.

Question 19

Clonic seizures EEG

Answer 19

The interictal EEG background depends on the underlying etiology of epilepsy. Generalized epileptiform discharges can be seen. The ictal discharge is usually a complex discharge of 10Hz recruiting rhythm mixed with activity of different frequency over different scalp regions fluctuating over time. Peaking of muscle activity does not coincide with EEG activity. In the postictal state, generalized slow activity can be seen.

Question 20

In what syndromes/conditions/circumstances are tonic seizures seen?

Answer 20

Tonic seizures are predominantly seen in epilepsies associated with abnormal neurocognitive examination and abnormal EEG background, classically defined as symptomatic generalized epilepsies. Examples include Lennox–Gastaut syndrome and inverted duplication of chromosome 15.

Question 21

Tonic seizures semiology

Answer 21

The semiology of tonic seizures consists of rapid flexor contraction of muscles, starting in body axis associated with loss of awareness, followed by tonic muscle contraction in the arms and legs. In a pure tonic seizure, there is no clonic event following the tonic activity. Tonic seizures usually last 5–20s but can last up to a minute.
They can be occasional or very frequent. Falls usually occur if the patient is standing.

Question 22

Tonic seizures EEG

Answer 22

The interictal EEG and Ictal EEG are variable depending on the epilepsy syndrome. Typically, the ictal EEG consists of the following: The most common ictal pattern consists of rhythmic spiking at 10–25Hz of low-amplitude desynchronized rhythm of 100μV. Another pattern is that of diffuse high-amplitude slow-wave discharges at theta and delta frequency over the vertex region, lasting 0.5–1s. This is followed by rapid 10–15Hz rhythm increasing in amplitude over the next 5–10s. The interictal EEG and Ictal EEG are variable depending on the epilepsy syndrome. Typically, the ictal EEG consists of the following: The most common ictal pattern consists of rhythmic spiking at 10–25Hz of low-amplitude desynchronized rhythm of 100μV. Another pattern is that of diffuse high-amplitude slow-wave discharges at theta and delta frequency over the vertex region, lasting 0.5–1s. This is followed by rapid 10–15Hz rhythm increasing in amplitude over the next 5–10s.

The ictal patterns tend to occur in series and last for minutes with seizures occurring every 20–30s.

Question 23

In what syndromes/conditions/circumstances are atonic seizures seen?

Answer 23

These are also predominantly seen in symptomatic generalized epilepsies. Such patients tend to have severe developmental delay and cognitive impairment as in Lennox–Gastaut syndrome.

Question 24

Atonic seizures semiology

Answer 24

Semiology: Brief atonia can be limited to the head or can involve all postural muscles. Loss of consciousness is extremely brief and patients can stand up immediately after a fall. When atonia is prolonged, patients will lay motionless on the floor. Falls occur on the body axis. The arms are not involved by tonic or myoclonic phenomenon. In mild cases, only upper body is involved, and in severe cases, the lower body can be involved.

Question 25

Atonia seizure EEG

Answer 25

The interictal EEG is not specific and can show slow spike-and-wave activity. EMG when recorded shows silence for ~400 ms or polyspike-and-wave activity. The ictal EEG shows generalized spike-and-wave activity wit atone coinciding with slow activity (this pattern is most often seen). Other ictal patterns can be seen, including low- or high-voltage fast activity and flattening or burst of polyspike-and-waves followed by generalized slow wave activity.

Question 26

Answer 26