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Figure 3–1 (Continued) (C) frontal intermittent rhythmic delta activity (FIRDA). (From Drazkowski J. Use of EEG in a consultative role. Semin Neurol 2000, 23: 296, Fig. 1; 300, Fig. 6; 302, Fig. 8. Reprinted by permission.)

v.rhythmic delta activities: typically are associated with subcortical or even brainstem lesions when the background rhythm is otherwise normal

(1)frontal intermittent rhythmic delta activity (FIRDA): occurs in adults, particularly with renal or hepatic encephalopathies or hydrocephalus

(2)occipital intermittent rhythmic delta activity (OIRDA): occurs in children, particularly in the context of absence epilepsies

vi.periodic lateralizing epileptiform discharges (PLEDS): focal bursts epileptiform discharges that occur repetitively every 1–5 seconds; indicates acute or subacute focal cortical injury, or occasionally a metabolic disorder (particularly nonketotic hyperglycemia) superimposed on a chronic, focal cortical injury

(1)bilateral PLEDS is suggestive of diffuse cortical injury or encephalopathy

2.Prolactin level: Useful only if collected within 15–20 minutes of the seizure

a.prolactin levels are increased over baseline level in 80% of generalized seizures and 70% of complex-partial seizures

b.prolactin levels are rarely increased after pseudoseizures, after prefrontal seizures that symptomatically resemble the bizarre behaviors of pseudoseizures {pseudo-pseudoseizures}, or after status epilepticus

c.seizures also increase CRH and LH secretion (Box 3.2)

II. Partial Seizures

1.Simple partial seizures (Fig. 3–2): do not involve impairment or loss of consciousness irrespective of the complexity or distribution of convulsive activity; form the aura of complex partial seizures

Box 3.2

Recurrence of Seizures: Overall risk of seizure recurrence is 40% after two years.

Low-recurrence risk with idiopathic or cryptogenic seizures and a normal EEG (25%)

Medium-recurrence risk with an abnormal neurological exam, neuroimaging, or EEG (50%)

High-recurrence risk with an abnormal neurological exam, neuroimaging, and EEG (65%)

The likelihood of developing epilepsy is increased by having antecedent conditions associated with an increased risk of epilepsy, seizures occurring during sleep, a family history of seizures, an abnormal EEG, particularly one with epileptiform abnormalities, or partial seizures

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i.primary motor cortex focus (Brodmann area 4): causes clonic or tonic-clonic movements according to the motor homunculus; rarely causes weakness without movements

(1)Jacksonian march—progression of convulsive movements as the epileptiform activity migrates along the motor homunculus

ii.supplementary motor area focus (Brodmann area 6): frequent, brief seizures occurring in clusters with a rapid onset and offset; posturing usually involves the contralateral upper extremity and contraversive head and eye deviation {fencer’s position}

iii.premotor cortex focus (Brodmann area 6) and frontal eye field focus (Brodmann area 8): cause unilateral forced gaze and head deviation {version seizures}, which are reliably contralateral only when the focus is in the frontal eye field

(1)may involve a decrease in the level of consciousness, which would be better classified as a complex-partial seizure

iv.insula cortex focus: typical symptomatic progression involves abnormal laryngeal sensation, followed by dysarthria with perioral and/or contralateral body paresthesias, and finally contralateral convulsions in the face and/or arm (Box 3.3)

v.frontal operculum focus: causes bilateral facial movements accompanied by mastication, salivation, and swallowing after an aura consisting of epigastric sensations, fear, and/or autonomic phenomena; may cause speech arrest or vocalizations with foci in either hemisphere, or a Broca’s-type aphasia with a focus in the dominant hemisphere

vi.dorsolateral prefrontal cortex focus: causes contralateral forced head and gaze deviation

b.simple partial sensory seizures

i.parietal lobe focus: most seizure foci are in the primary somatosensory cortex (Brodmann areas 3-1–2), which causes contralateral tingling and/or numbness according to the sensory homunculus that frequently progresses to frank motor seizure activity after a period of general tremulousness

(1)sensory symptoms can have a Jacksonian march equivalent

(2)negative seizure phenomena with parietal seizures

(a)loss of awareness of a body part {asomatognosia} can occur with nondominant hemisphere seizures

(b)receptiveor conductive-like aphasias can occur with dominant hemisphere seizures

(3)pain or temperature sensations, or bilateral sensations suggest involvement of the secondary somatosensory cortex (Brodmann area 40)

(4)the sensation of vertigo (10%), sinking, choking, or nausea indicates inferior parietal lobe involvement

(5)changes in affect may also be associated with parietal lobe seizures

ii.primary visual cortex focus (Brodmann area 17): causes elementary visual sensations (flashes, scotoma, hemianopia, amaurosis)

(1)seizures often involve tonic eye contraversion, oculoclonic, or nystagmoid eye movements, forced eye closure, eyelid fluttering, sensory hallucinations of eye movements, or even the sensation of eye pain

iii.occipito-parieto-temporal junction focus: causes complex imagery or hallucinations; frequently visualized objects are recognizable but are distorted in size {micropsia, macropsia} and/or shape {metamorphopsia}

iv.temporal lobe focus: two thirds of seizure foci are mesial; one third are lateral (i.e., neocortical)

Box 3.3

Gelastic Seizures

Related to hypothalamic hamartomas but EEG identifies epileptiform activity in frontal or temporal lobes

Laughter begins in childhood; later involves drop attacks, generalized seizures, cognitive impairment, precocious puberty, and behavioral disorders

Treatment: lamictal or clonazepam; surgery, particularly stereotaxic

Table 3–1 Complex Partial Versus Absence Seizures

(1)causes auditory or olfactory hallucinations, emotional, or psychic symptoms (e.g., flashbacks, déjà vu, jamais vu), sensations of vertigo, and autonomic changes (e.g., epigastric rising sensation, GI upset with nausea and hypermotility, respiratory arrest)

(a)olfactory hallucinations are usually unpleasant, indicating medial temporal lobe involvement {uncinate fits}

(b)gustatory sensations suggest involvement of the temporal opercular cortex

(2)rare manifestations include forced thinking (a rapid recollection of past life experiences), depersonalization, extremes in affect, or rage

2.Complex partial seizures: involves some impairment of consciousness without tonic-clonic activity; does not have to involve a complete loss of consciousness (Table 3–1)

a.general pathophysiology: 40% of cases have seizures that are initiated by a temporal lobe focus, either mesial or neocortical

b.general symptoms: can begin with a simple partial seizure that serves as an aura, or with outright impairment of consciousness

i.complex partial seizures often involve coordinated involuntary movements

(1)reactive automatism: a reaction to the environment (i.e., drinking from a cup that is placed in the hands)

(2)perseverative automatism: the persistence during a seizure of a complex action that was being performed before the seizure onset

c.mesial temporal cortex seizure foci: typically begins with auras consisting of epigastric sensations, fear, and/or oro-alimentary automatisms

i.mesial temporal/hippocampal sclerosis

(1)subtypes: do not correlate with seizure severity or responsiveness to treatment

(a)classic mesial temporal sclerosis: cell loss in the hilum of the dentate gyrus, the tip of the CA4 region, and the CA1subiculum interface; the CA2 region is relatively preserved (Box 3.4)

(b)minimal mesial temporal sclerosis: cell loss in the hilum of the dentate gyrus

(c)total mesial temporal sclerosis: cell loss in the dentate gyrus and CA1–4 regions

(2)histology: sclerosis implies neuron loss and gliosis in the affected regions

(a)50% of cases exhibit bilateral sclerosis but usually it is asymmetric

(b)20% of cases coexist with another pathological process (e.g., cortical dysplasia, tumor)

Partial Seizures

Box 3.4

The CA2 region is particularly susceptible to damage from status epilepticus.

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(3)pathophysiology: unknown cause but often disease onset is preceded by febrile seizures

(a)atrophy of the mesial temporal lobes exists at the time of seizure onset, and can be observed even in neonates

(b)mesial temporal sclerosis exhibits familial segregation, so it likely has a genetic predisposition

(4)specific diagnostic testing: EEG demonstrates spike-and-wave complexes in the inferior temporal leads or low-voltage beta activity at seizure onset that remains local for several seconds before spreading; best observed with subdural/depth electrodes

d.neocortical temporal foci: seizures often begin with auditory hallucinations, vertigo, or visual misperceptions; language disturbance can occur with foci in the dominant hemisphere

i.musicogenic seizures: a type of reflex seizure (Box 3.5) that is triggered by music (e.g., a particular composition, the sound from a certain instrument, or discussing or thinking about music)

(1)not the same as a seizure involving the perception of sound or musical notes {musical partial seizure}, wherein the perceived sound tends to be relative unformed (e.g., ringing, whistling)

e.frontal lobe seizure foci: cause complex and bizarre motor automatisms (e.g., eyelid fluttering, repetitive bilateral movements) that occur in clusters, often with minimal post-ictal confusion; frequently are confused with pseudoseizures

i.frontal operculum focus: causes auditory or visceral auras and visceral motor phenomena (salivation, spitting, vomiting)

ii.cingulate cortex or supplementary motor area (Brodmann area 6) focus: cause asymmetric bilateral posturing movements with automatisms; cingulate foci may cause gesturing, simple sexual behavior, or ictal laughter

iii.frontopolar cortex focus: causes forced thinking, aversive head movements, and/or axial clonic jerks

iv.orbitofrontal cortex focus: causes complex motor automatisms and olfactory hallucinations due to involvement of the cortex overlying the septal nuclei that receives the medial olfactory stria; may involve formed vocalizations (e.g., cursing)

v.dorsolateral frontal cortex focus: causes tonic posturing and speech arrest

3.Diagnostic testing: Scalp EEG gives adequate localization in only 50% of cases with temporal foci, and is even worse with frontal lobe foci; a single EEG demonstrates abnormalities in 40% of possible seizure cases, which is increased to 75% with prolonged EEG monitoring

a.ictal EEG patterns of complex partial seizures

i.rhythmic spike and wave activity, which are bilateral in 30% of cases

ii.rhythmic 5–7 Hz activity without spikes

iii.focal attenuation of background activity

Box 3.5

Reflex Seizure Triggers

Visual patterns (as in 3% of all epilepsies)

Tactile stimuli: hot water, body postures

Problem-solving

Reading, writing, or speaking

Specific movements

Startle involving any kind of stimulus

Figure 3–3 Generalized tonic-clonic seizure. (From Mumenthaler M. Neurological Differential Diagnosis. 2nd ed. Stuttgart, Germany: Georg Thieme; 1992, Fig. 1, p. 1. Reprinted by permission.)

iii.tonic phase: contracture of the axial musculature with upward eye deviation, pupillary dilation, and forced expiration of air {epileptic cry}; usually involves some decerebrate posturing

(1)tongue and jaw muscle tonus causes perioral injury, typically lateral tongue biting

(2)frequently patient becomes cyanotic, tachycardic, and hypertensive

iv.clonic phase: starts as low-amplitude, high-frequency ( 8 Hz)

convulsive movements of the extremities thorax and abdomen that progresses to high-amplitude, low-frequency ( 4 Hz) movements

(1)development of atonia breaks the seizure and causes incontinence

(2)bilaterally asynchronous movements may be caused by separate unilateral seizure foci, but this is rare

v.post-ictal phase: patient is poorly responsive and hypotonic; confusion and memory impairment may last a few minutes to hours, occasionally followed by psychiatric changes (depression, psychosis, anxiety, irritability) that can persist for a day

(1)post-ictal phase involves generalized fatigue, soreness, and migraine headaches

(2)laboratory testing during the post-ictal phase demonstrates respiratory-metabolic acidosis, hyperglycemia, and mild cerebrospinal fluid pleocytosis

b.epidemiology: unlike most other seizure types, occurs with similar incidences across all ages

c.diagnostic testing (Fig. 3–3)

i.ictal EEG: bilateral hemispheric involvement from the seizure onset that is bilaterally synchronous; refined computer analysis may identify asynchronous ictal onset, but this is not necessarily exclusive of a primarily generalized seizure

(1)immediate pre-tonic-clonic phase: any myoclonic or clonic activity is represented as a generalized burst of spike or polyspike activity

(2)tonic phase: identified by an abrupt decrease in voltage with diffuse 20–40 Hz activity {desynchronization pattern}; 8–10 Hz sharp waves build in amplitude during the tonic phase

(3)clonic phase: 8–10 Hz sharp waves of the late tonic phase are replaced by polyspike-and-wave pattern that slows to 4 Hz

(4)post-ictal phase: diffuse suppression of EEG activity with a lowvoltage delta frequency predominance

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ii.interictal EEG: 50% show epileptiform activity with 5 days of a seizure, and the yield is higher closer to the time of the seizure

(1)subtypes of interictal abnormalities: often multiple subtypes occur in the same patient

(a)multifocal spike complexes

(b)3–5 Hz spike-and-wave complexes (usually are bilateral with frontocentral predominance)

(c)irregular spike-and-wave complexes

(2)anticonvulsants tend to slow the background rhythm, except for barbiturates and benzodiazepines, which characteristically increase the beta activity in the 14–20 Hz range

iii.cerebrospinal fluid: any post-ictal pleocytosis should be assumed to be caused by an inflammatory process until proven otherwise

2.Tonic seizures

a.symptoms: diffuse contraction of the axial musculature, sometimes involving the proximal limbs or proximal and distal limbs; paralysis of respiration causes apnea

i.often results in the patient falling {drop attack}, so tonic seizures are frequently confused with atonic seizures

ii.startle seizures—a type of reflex seizure that is usually tonic in nature, triggered by the sudden or unexpected presentation of a stimulus (Box 3.6)

(1)specific symptoms: the seizure follows a startle response (i.e., eye closure with facial grimacing and flexion of the limbs and trunk) induced by a sudden stimulus of any type

(2)often occurs in children with diffuse cerebral abnormalities (e.g., Down’s syndrome, anoxic encephalopathy)

(3)treatment: benzodiazepines, carbamazepine, lamotrigine

b.diagnostic testing: subtypes of ictal EEG patterns

i.sudden reduction of background activity {electrodecremental response} (Fig. 3–4)

ii.bilaterally synchronous 15–25 Hz activity with increasing voltage

iii.diffuse high-voltage 10 Hz activity

iv.diffuse theta or delta activity

Box 3.6

Hyperekplexia

A hyperactive startle response followed by rigidity leading to falls (no impairment of consciousness)

Caused by glycine receptor mutations; treat with clonazepam

Status Epilepticus

Box 3.7

Epilepsia partialis continua—spontaneous, regular or irregular clonic epileptic movements that last for long periods of time

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a.thiamine 100 mg IM 50 mL of D50 IV (adult) or 2 mL/kg D25 IV (pediatric) should be routinely administered to all status epilepticus patients considering the possibility of Wernicke’s encephalopathy

b.continuous EEG monitoring is indicated when the patient becomes overly sedated and is not overtly seizing to evaluate for subclinical status epilepticus

4.Prognosis: 3–30% mortality, depending upon the cause, duration, and patient age

a.outcome is worse with prolonged seizures because of the development of hypoglycemia, hypotension, and/or acidosis

b.cognitive dysfunction is often the residual of status epilepticus

V. Inherited and Pediatric Seizures

A. Neonatal Seizures

1.Subtypes: generalized seizures do not exist in neonates because myelination is incomplete, thereby preventing spread of epileptiform activity

a.focal clonic seizures: usually caused by focal cerebral injury; Jacksonian march does not occur in neonates because of the lack of myelination

b.multifocal clonic seizures: involve random migration of seizure activity across several muscle groups; usually occurs after diffuse cerebral injury, particularly severe hypoxic encephalopathy

c.tonic seizures: extension and stiffening of the body with apnea and upward eye deviation

i.usually caused by focal cerebral injury or by intraventricular hemorrhage in premature infants; very poorly localized with EEG, may involve a brainstem release mechanism that accounts for the majority of symptoms

d.myoclonic seizures: rare in neonates; can be misinterpreted as a generalized seizure; usually are caused by diffuse cerebral injury in the children of drug-addicted mothers

e.“subtle” seizures: involves tonic eye deviations (most diagnostic symptom for this condition), sucking behavior, and/or cycling movements of the extremities

2.Causes (Table 3–3)

a.severe hypoxic encephalopathy: symptoms also include stupor or coma, hypotonia, multiple cranial nerve palsies; EEG demonstrates slow-wave, flat-line, or burst-suppression EEG

i.usually occurs in fetuses with irregular heart rates or meconium aspiration

Table 3–3 Causes of Neonatal Seizures

ii.seizures from severe hypoxic encephalopathy are difficult to control because of elevated intracranial pressure but become manageable with a lowering of the pressure

b.mild hypoxic encephalopathy: symptoms also include lethargy, jitteriness, and sympathetic hyperactivity (tachycardia, dilated pupils); unlike severe hypoxic encephalopathy, the EEG is relatively normal

i.mild hypoxic encephalopathy does not cause seizures except when provoked by hypoglycemia or an electrolyte disturbance

c.trauma: usually occurs in large-for-gestational-age neonates after complicated deliveries; often associated with intracranial hemorrhage

d.intracranial hemorrhage

i.subarachnoid hemorrhage in neonates is more likely caused by ruptured superficial veins than arteries

ii.subdural hemorrhage in neonates is caused by disruption of the veins on the tentorium near the falx due to excessive vertical head molding

e.hypoglycemia: defined as blood glucose 20 mg/dL in premature infants or 30 mg/dL in fullterm infants; occurs in 10% of all neonates

i.symptoms also include apnea, vomiting, hypotonia, seizures; progression to coma during hypoglycemia is associated with long-term neurological impairment

f.hypocalcemia: may exacerbate seizures but is not likely their underlying cause

B.Pediatric Seizures

1.Febrile seizures

a.pathophysiology: convulsions that are not necessarily associated with a rising or peak body temperature; exhibits an autosomal dominant inheritance with incomplete penetrance

i.subtypes

(1)simple febrile seizures (70%): a generalized tonic-clonic seizure that lasts 1 minute; no further seizures occur in the next 24hour period

(2)complex febrile seizures (30%): a seizure with focal or multifocal features that lasts 15 minutes, or that recurs within 24 hours

ii.epidemiology: occur in 3% of children

(1)3% of febrile seizure children will ultimately develop epilepsy

(2)40% of children with a single febrile seizure will have a second febrile seizure, and 50% of children with two febrile seizures will have a third febrile seizure

(a)the risk of further febrile seizures is increased by having

(i)the first seizure at age 1 year

(ii)a seizure with a body temperature 40°C

(iii)an abnormal neurological exam or developmental delays

(iv)prolonged, focal-onset, or multiple episodes of febrile seizures

(v)a family history of seizures

iii.febrile seizures are triggered by the measles–mumps–rubella (MMR) vaccine (that induces a fever), but this does not increase the risk of developing epilepsy over that of febrile seizures not caused by a vaccination

b.diagnostic testing

i.cerebrospinal fluid analysis to rule-out meningitis or encephalitis, particularly in children 6 months old; however, 90% of children with meningitis or encephalitis are obtunded after a seizure, which is rare with simple febrile seizures

(1)lumbar puncture is not necessary if child recovers rapidly and completely after the seizure, and if the fever is readily explained by an extracranial source of infection

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ii.EEG and neuroimaging are indicated only if child has an abnormal neurological exam or atypical febrile seizures

c.treatment: no treatment is indicated after simple febrile seizures; antiepileptic medications are indicated for complex febrile seizures, febrile seizures in patients 1 year of age, and patients with an abnormal neurological exam

2.Generalized myoclonic seizures

a.infantile spasms/West’s syndrome (Box 3.8)

i.pathophysiology: 75% of cases have an underlying structural lesion (e.g., a phakomatosis), acquired cerebral injury (e.g., intracranial hemorrhage or infection), or genetic abnormality (e.g., non-ketotic hyperglycinemia, Down’s syndrome)

ii.symptoms: onset between 4–6 months of age

(1)seizures: classically manifests as clusters of symmetric extensor and/or flexor movements, followed by tonic contractions lasting10 seconds; seizures most commonly occur after waking

(a)abdominal flexions are often mistaken for colic

(2)autism

(3)progressive mental retardation (usually in patients with an underlying malformation)

(4)microcephaly

(5)focal neurological injury (60%): can be cortical or subcortical (e.g., athetosis) in nature

iii.diagnostic testing

(1)interictal EEG demonstrates a chaotic background with randomlydispersed high-voltage slow waves and spike discharges across all leads {hypsarrhythmia} (Fig. 3–5)

(a)the multifocality of hypsarrhythmia is replaced within a few months by generalized synchronous discharges, which eventually degrade into a slow spike-and-wave discharge similar to Lennox-Gastaut syndrome by 2 years of age

(2)ictal EEG demonstrates background suppression during the convulsive movements {electrodecremental response} (Fig. 3–4), high-voltage generalized slow waves, and/or paroxysmal lowvoltage fast activity

(3)in the absence of an underlying structural lesion on neuroimaging, combined positron emission tomography (PET) scanning and video EEG monitoring may identify an area of cortical abnormality

Box 3.8

Aicardi’s Syndrome

Infantile spasms agenesis of the corpus callosum retinal malformations

Exhibits X-linked dominant inheritance (a hemizygous lethal phenotype in males)

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(1)does not involve mental retardation

ii.diagnostic testing: interictal EEG is normal; ictal EEG identifies generalized polyspike or spike-and-wave discharges during myoclonic jerks

(1)EEG during sleep exhibits exaggerated discharges that occur with or without myoclonic jerks

iii.treatment: valproate

d.severe myoclonic epilepsy (Box 3.10)

i.pathophysiology: unknown, but appears to have a familial predilection

ii.symptoms: develops by 1 year of age; typically begins as a febrile seizure that then exhibits nonfebrile clonic seizures, with the eventual development of myoclonus within several years

(1)interictal neurological deficits (e.g., gait ataxia, dystonia, weakness) also develop

(2)associated with mental retardation

iii.diagnostic testing: EEG eventually demonstrates spontaneous and photic stimulation-induced bursts of generalized spike-and-wave activity with a reduction in background activity

iv.treatment: resistant to therapy

e.juvenile myoclonic epilepsy

i.pathophysiology: autosomal dominant inheritance of unknown genetic factors

ii.symptoms: seizures involve bilateral but asymmetric flexor movements of the upper extremities or rarely of the lower extremities that develop most commonly after awakening; no loss of consciousness occurs with seizures

iii.diagnostic testing: interictal EEG demonstrates bilateral, symmetric 3.5–6 Hz spike-and-wave and polyspike discharges; ictal EEG exhibits diffuse polyspike activity followed by 1–3 Hz slow waves (Fig. 3–7)

(1)photic stimulation provokes discharges

iv.treatment: valproate

Box 3.10

Ohtahara’s Syndrome/Infantile

Epileptic Encephalopathy

Symptoms: onset shortly after birth, up to 3 months of age, rarely begins in utero; involves tonic spasms, erratic motor clonic movements, and/or hemiconvulsions

Diagnostic testing: clusters of burstsuppression

Treatment: seizures are poorly responsive; may attempt ACTH, vigabatrin, valproate, or benzodiazepines; avoid carbamazepine, which increases seizure frequency

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(ii)progression of aphasia not related to frequency of seizures, and is fluctuant

(iii)auditory agnosia may occur with involvement of the nondominant hemisphere

(b)focal or generalized seizures, usually atonic (70%)

(c)behavioral changes: hyperactivity, aggression

(3)diagnostic testing: EEG demonstrates multifocal cortical spike discharges predominantly in the temporal and parietal lobes that are bilateral in 90%; these EEG abnormalities are minimal or even absent during waking, but become so severe during sleep (particularly at sleep onset) as to be nearly continuous

(4)treatment

(a)glucocorticoids often improve seizures and aphasia

(b)antiepileptic drugs control seizures but has an unclear effect on aphasia

(c)subpial transection to isolate seizure focus, or have surgical resection of seizure focus improve seizures and aphasia

(5)prognosis: seizure always remit by age 15; aphasia may persist into early adulthood before improving

ii.acquired epileptiform opercula syndrome

(1)pathophysiology: exhibits autosomal dominant inheritance with anticipation

(2)symptoms: oral dysphasia and an inability to perform complex facial movements {facial apraxia} associated with focal or generalized seizures

(3)diagnostic testing: ictal EEG demonstrates centrotemporal discharges

(4)treatment: completely unresponsive to treatment

iii.autosomal dominant nocturnal frontal lobe epilepsy

(1)pathophysiology: mutation of the presynaptic nicotinic acetylcholine receptor 4 subunit causing a decreased calcium conductance of the channel; exhibits autosomal dominant inheritance with 70% penetrance

(2)symptoms: seizures begin with vocalization or a psychic prodrome that wakes the patient from sleep, followed by tonic-clonic movements without loss of consciousness; occur only during sleep, often in clusters

(a)previously was considered a movement disorder (“nocturnal paroxysmal dystonia”)

(3)diagnostic testing: normal interictal EEG in 85%; requires continuous video monitoring to distinguish from REM sleep behavior disorder

(4)treatment: carbamazepine

iv.benign occipital epilepsy

(1)pathophysiology: unknown; frequently occurs in patients with migraine; not associated with structural lesions

(2)symptoms: seizures involve unformed visual hallucinations, visual illusions (micropsia, macropsia, metamorphopsia), vision loss (either complete or hemianopic), vomiting and drooling, and/or forced blinking and forced gaze deviation; some patients will have seizures followed by a loss of consciousness lasting several hours

(a)seizures usually develop after a migraine headache, and after the patient will typically have a migraine headache

(b)seizures usually occur at sleep onset

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(3)diagnostic testing

(a)EEG demonstrates continuous focal spike discharges that spread to contiguous areas of cortex, and eventually mirror foci on the contralateral hemisphere

(b)neuroimaging: may be normal initially, but hemispheric atrophy and ipsilateral hydrocephalus ex vacuo develop within 6 months

(c)PET and single photon emission computed tomography (SPECT) scanning demonstrate hypometabolism and decreased cerebral blood flow over large areas of the affected hemisphere

(d)cerebrospinal fluid analysis is usually normal

(4)treatment: refractory to antiepileptic medications, immunosuppressive agents, and antiviral therapy; early hemispherectomy can be curative

b.complex partial seizures: epileptogenic focus is usually in the temporal frontal or parietal lobes

i.general symptoms: staring spells, automatic behaviors (e.g., facial grimacing, hand wringing), posturing, or loss of body tone lasting 1–2 minutes

(1)post-ictal confusion and lethargy can occur with or without secondary generalization

(2)30% of patients exhibit an aura consisting of a nondescript unpleasant feeling, auditory hallucination, or abdominal discomfort; auras are particularly common with mesial temporal foci

ii.subtypes

(1)autosomal dominant partial epilepsy with auditory features

(a)genetics: caused by mutations of leucine-rich glioma- inactivated-1 gene (LGI-1), which has an unknown function (Box 3.14)

(b)specific symptoms: seizures involve unformed sounds (e.g., clicks, buzzing), changes in sound perception (e.g., deafness, muffling, increase in volume), or complex sounds, then usually progresses to a psychic symptom (e.g., déjà vu)

(i)30% of patients have unilateral symptoms

(ii)some patients with familial seizures exhibit a Wernicke’s- type aphasia at the seizure onset

(iii)seizures may be triggered by sounds

(2)benign familial neonatal convulsions

(a)genetics: caused by mutations in the voltage-gated potassium channel KCNQ-2 gene (chromosome 20) and KCNQ-3 gene (chromosome 8); abnormal channels reduce the repolarizing potassium current, allowing prolonged neuronal depolarization

(b)specific symptoms: clonic or apneic seizures that occur in clusters within the first few postnatal days

(c)prognosis: seizures resolve by a few months of age

(3)benign familial infantile convulsions

(a)genetics: most cases are linked to poorly defined abnormalities on chromosome 16; cases associated with familial hemiplegic migraine are caused by mutations of ATP1A2 sodium-potassium ATPase gene on chromosome 1

(b)specific symptoms: seizure onset between 3–12 months of age; otherwise normal development, and seizures remit by adulthood

(i)can be associated with familial hemiplegic migraine

(4)benign familial neonatal-infantile convulsions

Box 3.14

LGI-1 is located in the loss of heterogeneity region on chromosome 10 in glioblastoma multiforme (see p. 120)

(a)genetics: caused by mutations in the SCN2A gene for voltagegated sodium channel

(b)specific symptoms: clonic seizures developing within first few postnatal weeks, which is later than benign familial neonatal convulsions but earlier than benign familial infantile convulsions

iii.treatment: carbamazepine, phenytoin, primidone, valproate; surgical removal of medically refractory seizure foci

C. Nonseizure Paroxysmal Disorders of Children

1.Pediatric apnea syndromes

a.periodic breathing—irregular respiratory pattern with intermittent pauses of 3–6 seconds duration, followed by 10–15 seconds of hyperventilation without associated autonomic changes; seen mostly in premature infants due to immaturity of the brainstem respiratory centers

b.true apnea—cessation of breathing 15 seconds, or 15 seconds if associated with bradycardia

i.can be considered normal if the patient is 3 months of age and if the apnea is not associated with tonic eye deviation, limb stiffening, or clonic movements

(1)seizure-induced apnea rarely is associated with bradycardia

2.Jitteriness—an excessive response to stimulation characterized by a lowfrequency, high-amplitude shaking of the limbs and jaw; can be confused with myoclonic seizures but jitteriness is more rhythmic

a.jitteriness occurs in the newborns of drug-abusing mothers (particularly those using cocaine and methadone) or mothers using phenothiazines or propoxyphene, in newborns with perinatal hypoxia, or in newborns with metabolic disorders, therefore it has a high coincidence with seizures

b.identify episodes of jitteriness by a normal EEG, the absence of eye movements, and the lack of change in respiration; jittery neonates also have a hyperactive Moro reflex

c.treatment: paregoric; phenobarbital

3.Breath-holding spells

a.pathophysiology: a type of syncope thought to be related to immaturity of the brainstem respiratory centers; exhibits autosomal dominant inheritance with incomplete penetrance

i.breathing stops after expiration (not after inspiration) in response to an adverse stimuli

b.subtypes

i.pallid breath-holding spells—breathing stops in response to a painful stimulus; the child often falls asleep after the breath-holding spell but is otherwise normal

ii.cyanotic breath-holding spells—breathing stops during a crying episode; long episodes can exhibit tonic posturing, extremity trembling, and upward eye deviation; recovery is rapid without any post-ictal confusion

(1)EEG during the breath-holding spell is low-voltage and nonepileptiform

VI. Pseudoseizures/Nonepileptiform

Seizures (Box 3.15)

1.Pathophysiology a. subtypes

i.posttraumatic pseudoseizures: develop in response to physical, psychological, or sexual abuse

Box 3.15

Pseudo-Pseudoseizures

Short duration ( 30 seconds) repetitive episodes with bizarre behavior (e.g., complex automatisms) and large movements (e.g., abduction of upper extremities)

Involve the epileptiform activity developing out of mesial frontal lobes or mesial parietal lobes

Epileptiform activity is EEG inaccessible; may require high-frequency filters to demonstrate theta activity in parasagittal leads

Pseudoseizures/Nonepileptiform Seizures

99

3 Seizures and Epilepsy

ii.developmental pseudoseizures: develop in response to poor coping with increasingly complex developmental challenges or failure to achieve developmental milestones

b.other risk factors

i.comorbid psychiatric disorders: anxiety; depression; histrionic or borderline personality disorders

(1)pseudoseizures may represent the presentation of a conversion disorder

ii.family history of pseudoseizures

iii.head trauma

iv.pending disability claims

v.abrupt elimination of epileptiform seizures, as after seizure surgery

vi.epileptiform seizures

2.Epidemiology: more common in late adolescence and early adulthood as well as in women; rare at 5 years of age and 55 years of age

a.present in upwards of 30% of patients in specialty seizure clinics and 20% of adolescents with new-onset seizures

b.30% coincidence with epileptiform seizures

3.Symptoms: Seizure-like episodes without electroencephalographic epileptiform activity

a.symptoms differentiating pseudoseizures from epileptiform seizures: none are sufficiently accurate to ensure the diagnosis

i.clonic activity in which the limbs are out-of-phase with each other

ii.events occurring while the patient appears to be asleep but has EEG activity indicating wakefulness {preictal pseudosleep}

iii.pelvic thrusting

iv.eye movements or fluttering eyelids during the event

v.preserved recall of the event

vi.complex, well-formed vocalizations at the beginning of the event

(1)vocalizations are simple (e.g., grunting) and occur more commonly during the convulsive movements in epileptiform seizures

vii.incontinence: incontinence early in the course of pseudoseizures is rare, it often develops later after the patient is repeatedly questioned about it

viii.lip biting or biting the tip of the tongue is suggestive of pseudoseizures

(1)biting the side of the tongue is suggestive of epileptiform seizures

ix.typical events are inducible by suggestion (e.g., saline injection)

b.symptoms that are unable to differentiate pseudoseizures from epileptiform seizures: the presence of an aura, the duration of event, post-ictal confusion, physical trauma from events, prolonged course of events (i.e., there is a “pseudo-status epilepticus”

4.Diagnostic testing

Figure 3–9 Treatments for primary generalized seizures.

VII. General Treatment of Seizures

1.Medical treatment: Quality of life improves only with complete seizure control (Fig. 3–9; Fig. 3–10)

a. prophylactic antiepileptic medication use in patients with neurological disorder but without seizures

i.severe head trauma (prolonged loss of consciousness, amnesia, depressed skull fracture, contusion, or hematoma): prophylaxis does not reduce seizure rate

ii.brain tumor: prophylaxis does not seem to reduce development of seizures in patients with primary or metastatic tumors

iii.stroke: no indication, although it is routinely used short-term in subarachnoid hemorrhage patients because of the fear of increased intracranial pressure that accompanies seizures

b.discontinuing medication therapy

i.predictive factors for successful seizure remission (Box 3.16)

(1)the patient will most likely be seizure free if he or she has

(a)a single type of seizure

(b)had no seizures for 3.5 years

(c)a normalized EEG on antiepileptic treatment

(d)a normal neurological exam and intelligence quota (IQ)

i.general rules

(1)hepatic-inducing medications (e.g., lower other drug levels): phenytoin, carbamazepine, phenobarbital, primidone

(2)hepatic-suppressing medications (e.g., raise other drug levels): valproate

(3)albumin-binding medications (e.g., raise other drug levels): phenytoin, valproate

d.management of medication failures

i.if maximal doses of an antiepileptic medication fail to control the seizures, there is only a 10% likelihood of developing control over seizures by adding a second antiepileptic medication

ii.there is 5% likelihood of developing control over seizures by adding a third antiepileptic medication or by using multiple antiepileptic drugs after failing a second antiepileptic medication

Box 3.16

All four factors achieve 70% remission in children, and 60% remission in adults.

General Treatment of Seizures

3 Seizures and Epilepsy

2.Surgical treatment

a.preoperative evaluation involves

i.video-EEG monitoring

ii.neuroimaging: CT, MRI; ictal studies with SPECT or PET scanning

iii.invasive continuous monitoring with subdural electrodes

iv.Wada test evaluation of hemispheric dominance for language function and verbal memory

b.procedures

i.multiple subpial transections: vertical incisions that interrupt intracortical connections; can be used to isolate a seizure focus in eloquent cortex, leaving minimal neurological deficits (as in Landau-Kleffner syndrome where it is effective in 55% of cases)

ii.focal cortical resection: removal of a small block of epileptogenic cortex; 80% effective with temporal lobe foci, 50% effective with extratemporal foci

iii.temporal lobectomy: eliminates seizures in 70% of mesial temporal sclerosis cases

iv.hemispherectomy: for large blocks of epileptogenic cortex, as in Rasmussen’s syndrome where it is effective in 90%

v.corpus callosotomy: for multifocal seizures or unidentified epileptogenic foci that cause seizures with a high risk of physical injury (e.g., the drop attacks of tonic or atonic seizures)

c.vagal nerve stimulation: reduces frequency by 30% of either generalized or partial seizures; chief side effect is hoarseness during activation

i.likely acts by desynchronization of brain activity and/or by inhibition of epileptogenic foci by monoaminergic modulation

Also used for trigeminal neuralgia, bipolar disorder; avoid in absence, myotonic, atonic seizures

Target range 8–12 g/mL

*Not available in the United States. Abbreviations: bid, twice a day; IV, intravenously.

General Treatment of Seizures