SEIZURES AND EPILEPSY

IN CHILDREN

Epidemiology of Seizures and Epilepsy in

Children

● 4-6 % incidence of a single seizure

● 1% incidence of epilepsy (> 2 unprovoked seizures)

● 70-80 % achieve remission (―outgrow‖ seizures)

● HISTORY is the most important tool in differentiating a seizure from a non-seizure look-alike

● EEG is an adjunctive test to clinical history

● after 1st unprovoked seizure: ● If EEG normal, 40% recurrence risk

● If EEG abnormal, 80% recurrence risk

● 50% of 2nd unprovoked seizures occur within 6 months of 1st seizure

Epilepsy

● Definition: Two or more unprovoked seizures

that occur at interval greater than 24

hours (i.e recurrent seizures)

● Causes

● 1. Idiopathic (primary) in 80% of cases

● - Genetic basis exist for many epileptic syndromes

● 2. Organic (secondary) in 20% of cases

● - Congenital cerebral malformation.

● - Degenerative brain diseases.

● - Post-traumatic.

● - Post-hemorrhagic.

● - Post-infection.

● - Post-toxic.

● -Post-anoxic.

Absence (Petit Mal) Epilepsy

- Sudden onset of staring, interrupting speech or activity

- Occurs multiple times per day

- Short duration (seconds)

- Occurs in school aged children ~ 4-12 years, otherwise normal

● Frequency 8%

● Genetic predisposition- strong 20%

● Female preponderance 75%

● EEG: bilateral, synchronous, symmetrical 3 /

sec spike wave, normal background.

● Seizures: Very frequent simple absences.

● Rx: VPA or ESM with control in 70 - 80%.

● Evolution: Remission- 95%.

● Rare persistence of absences only- 6%

Childhood

Absence (Petit Mal) Epilepsy

EEG findings characteristic:

- bilateral generalized 3 Hz spike-and-wave discharges

- provoked by hyperventilation and photic stimulation

● EPILEPSYSYNDROMES

Infantile Spasms (West Syndrome) –

a severe epilepsy

Clinical spasms (1-2 secs)

- a subtle momentary flexion or

extension of the body

- occur in clusters when drowsy

(waking or falling asleep)

Severely abnormal EEG pattern:

disorganized, discontinuous,

high amplitude, multifocal spikes

called HYPSARRHYTHMIA

Treatment: ACTH

Infantile spasms

● may be mistaken for colic, reflux, hiccups, or a startle ! ● called symptomatic if etiology identified:

● brain insult at birth (ex. hypoxia-ischemia, meningitis) ● brain malformation ● neurocutaneous disorder (Tuberous Sclerosis) ● metabolic disorder

● called cryptogenic if NO identifiable cause ● prognosis best (10% good outcome) if idiopathic

● normal development at onset of infantile spasms

● extensive etiology testing negative

● prognosis poor for: ● seizure control (infantile spasms and future seizures) ● future neurocognitive and developmental abilities

Lennox-Gastaut Syndrome –

a severe epilepsy

● Often evolves from infantile spasms

● Neurodevelopmentally impaired children

● Syndrome defined by a TRIAD of:

● 1. mixed seizure types: atonic, atypical absence,

myoclonic, tonic-clonic, partial

● 2. developmental delay

● 3. abnormal EEG pattern: slow (< 2.5 Hz) spike wave

discharges

● Symptomatic or cryptogenic etiologies (like IS)

● Prognosis poor

Juvenile Myoclonic Epilepsy (JME)

Seizure types: - myoclonic in AM

- “grand mal”

- absence

EEG: bilateral generalized

4-6 Hz spike-wave or

polyspike-wave activity

Benign Rolandic Epilepsy

Aka Benign Focal Epilepsy of Childhood

with Centrotemporal Spikes

EEG has

characteristic

pattern:

bilateral

independent

centrotemporal

spikes

Benign Rolandic Epilepsy

● Treatment recommended only if:

● Seizures frequent (which is unusual)

● Socially stigmatizing if occur in wakefulness

● Anxiety provoking for parents if occur in sleep

● Effective treatments:

● Avoidance of sleep deprivation

● Medications: carbamazepine, oxcarbazepine

● Time (outgrown by adolescence)

Other Epilepsy Syndromes

● Rett Syndrome ● Occurs only in girls (X-linked lethal mutation)

● Initial normal development 🡪 dev regression / autistic (loss of motor / language / social skills)

● Acquired microcephaly (deceleration of head growth)

● Hand wringing / alternating hand movements

● Apnea / hyperpnea / breathholding

● Seizures

Partial (Focal) Epilepsy

● onset of seizure begins in one area of one cerebral hemisphere (apparent clinically or via the EEG)

● AWARE: no impairment of consciousness

● IMPAIRED AWARENESS: impairment of consciousness (staring)

● FOCAL TO BILATERAL TONIC CLONIC:partial seizure that ends in a generalized convulsion

● Most frequently involved brain regions: ● Temporal Lobe (80 %) >

Frontal Lobe >>

Parietal or Occipital

● MRI or CT:

● Normal or Abnormal

● Neurologic exam:

● Normal or Abnormal

Anatomic Onset of Focal Epilepsies

Mesiotemporal sclerosis

Spells that mimic seizures

● Apnea / ALTE ● GER ● Sleep disorders (nocturnal myoclonus, night terrors,

narcolepsy/cataplexy) ● Migraine variants (esp. aura) ● Benign breathholding spells

● No neuro consult / lab / EEG / CT, Fe for cyanotic type ● Syncope ● Movement Disorders (tics, tremor, dystonia) ● ADD ● Behavioral Stereotypies (PDD) ● Pseudoseizures (psychogenic seizures)

● Strange posturing, back arching, writhing ● Alternating L and R limb shaking during same seizure ● Psychosocial stressor

Treatment of epileptic seizures

● often not until after the second unprovoked seizure

● choice of AED based on maximum efficacy for that particular seizure type and minimal side effects

● 70% become seizure free on monotherapy

● an additional 15% become seizure free on polypharmacy

● 15% remain intractable

● Discontinue AED after 2 years seizure free EXCEPT for JME

● Alternate treatments:

● Ketogenic diet (high fat diet)

● Vagal nerve stimulator – FDA approved for partial seizures in 12 years+

● Epilepsy surgery

Classic side effects of AEDs

● valproic acid (Depakote): hepatotoxicity, weight gain,

acute pancreatitis

● lamotrigine (Lamictal): Stevens-Johnson syndrome

● phenytoin (Dilantin): gingival hypertrophy, acute ataxia, osteoporosis

● phenobarbital: adverse behavior / hyperactivity

● carbamazepine (Tegretol): agranulocytosis, aplastic anemia

● oxcarbazepine (Trileptal): hyponatremia

● ethosuximide (Zarontin): lupus-like reaction

● topiramate (Topamax): weight loss, acidosis, renal stones

● felbamate (Felbatol): aplastic anemia

● gabapentin (Neurontin): behavioral changes

Status Epilepticus

● Def: any type of seizure lasting > 5 minutes or repeated seizures without recovery between seizures.

● seizures > 1 hour are associated with neuronal injury due to glutamate excitotoxicity

● Evaluation and acute treatment for seizure > 5 minutes: ● ABC’s (RR, HR, BP)

● check temp, glucose, electrolytes, CBC, renal and hepatic function, AED levels

● Benzodiazepine 🡪 phenytoin 🡪 phenobarbital

Febrile Seizures

● 2-4 % of children age ~ 6 months – 6 years

● Provoked by a sudden spike in temp usually with URI, Acute OM, AGE (genetic predisposition)

● ―Simple‖

● Generalized convulsion (whole body shaking)

● Brief (< 15 minutes)

● Only one in the course of an illness

● Future risk of epilepsy (1%) SAME AS other children

● ―Complex‖

● focal seizure (one side of body shaking, staring)

● prolonged (> 15 minutes)

● multiple in 24 hours

● Complex febrile seizures hint at an increased risk of future epilepsy

Treatment of Febrile Seizures (not

epilepsy)

● Considered benign not warranting daily anti-seizure medication

● but phenobarbital or valproic acid provide some prevention

● Rectal Diastat (valium gel) may be used to: ● abort prolonged complex febrile seizure

● prevent complex febrile seizure clusters (if child known to cluster)

● prevent febrile seizure recurrence during a febrile illness

● Anti-pyretics have NOT been proven to decrease the risk of recurrent febrile seizures

PERIPHERAL NERVOUS SYSTEM

DISORDERS

Weakness (+/- sensory deficits)

with NO UMN signs—

no hyperreflexia, no clonus,

no upgoing toes

1. ANTERIOR HORN CELL A. Spinal Muscular Atrophy (SMA) (genetic), B. Poliomyelitis (acquired)

2. Peripheral nerve

3. Neuromuscular junction

4. Muscle

skin

● Anterior horn cell – there are signs of

denervation:

● Neuropathy – often distal nerves affected.. •

Myopathy – there is weakness (often

proximal)

● Neuromuscular junction –fatiguability

Investigations Myopathy:

● • Serum creatine phosphokinase – markedly

elevated in Duchenne and Becker muscular

dystrophy and inflammatory myopathies •

● Muscle biopsy, needle or open – modern

histochemical techniques often enable a

definitive diagnosis

● • DNA testing – to identify abnormal genes

Neuropathy:

● • Nerve conduction studies – to identify

delayed motor and sensory nerve conduction

velocities seen in neuropathy

● • DNA testing – for abnormal genes

● • EMG (electromyography) helps in

differentiating myopathic from neuropathic

disorders, e.g. fatiguability on repetitive nerve

stimulation in myasthenia.

DNA TESTS

● DNA available for

● spinal muscular atrophy (SMA),

● Duchenne muscular dystrophy,

● myotonic dystrophy, the

● congenital muscular dystrophies and

● hereditary neuropathies.

● allows antenatal testing and genetic

counselling and often obviatesthe need for the

discomfort of peripheral neurophysiology

A. Spinal muscular atrophy (SMA)

Type 1 SMA - Werdnig-Hoffman

● Prenatal – decreased fetal movements

● Neonatal / early infancy

● severe hypotonia

● breathing / swallowing difficulties

● absent reflexes

● tongue fasciculations

● no face / eye weakness

● Motor milestones: never sit

● Autosomal recessive - SMN (survival motor neuron) gene

mutation, chromosome 5

Spinal muscular atrophy

● This is an autosomal recessive .

● due to mutationsin the survival motor

neurone (SMN) gene.

● degeneration of the anterior horn cells,

● leading to progressive weakness and wasting

ofskeletal muscles .

SMA Muscle biopsy reveals

grouped atrophy

Spinal muscular atrophy type

1 (Werdnig–Hoffmann disease)

● presenting in early infancy

● Diminished fetal movements are often

noticed during pregnancy.

● and there may be arthrogryposis.

● Absent deep tendon reflexes •

● Intercostal recession •

● Fasciculation of the tongue.

● These children never sit unaided.

● Death is from respiratory failure within about

12 months.

Milder forms

● There are of the disorder with a later onset.

Children with

● type 2 spinal muscular atrophy can sit, but

never walk independently.

● type 3 (Kugelberg– Welander)

do walk and can present later in life.

Acute post-infectious polyneuropathy (Guillain–

Barré syndrome)

● 2–3 weeks after an upper respiratory tract infection or

gastroenteritis.

● The disorder is probably due to the formation of antibody

attaching itself to protein components of myelin.

● ascending symmetrical weakness with loss of reflexes.

● autonomic involvement.

● Sensory symptoms, usually in the distal limbs,.

● Involvement of bulbar muscles leads to difficulty with

chewing and swallowing and the risk of aspiration.

B. Poliomyelitis (infantile paralysis)

● viral infection -> destruction of anterior horn

cells

● flaccid asymmetric paralysis, usually legs

● may involve face (bulbar muscles)

● decreased or absent reflexes

GBS

● Respiratory depression may require artificial

ventilation.

● The maximum muscle weakness may occur

only 2–4 weeks after the onset of illness.

● Although full recovery may be expected in

95% of cases, this may take up to 2 years

GBS Ix:

● The CSF protein is characteristically

markedly raised, but this may not be seen

until the second week of illness.

● The CSF white cell count is not raised.

● Nerve conduction velocities are reduced.

GBS Management

● supportive, particularly of respiration.

● Corticosteroids have no beneficial effect and

may delay recovery.

● immunoglobulin infusion. If this is not

successful, plasma exchange may be

effective

Bell palsy

● Bell palsy and facial nerve palsies Bell palsy

is an isolated lower motor neurone paresis of

the VIIth cranial nerve leading to facial

weakness

Myasthenia gravis

● This presents as abnormal muscle

fatiguability which improves with rest or

anticholinesterase drugs.

Juvenile myasthenia

● This is similar to adult autoimmune

myasthenia

● is due to binding of antibody to

acetylcholine receptors on the post-

junctional synaptic membrane.

● This gives a reduction of the number

of functional receptors.

●

Juvenile myasthenia

● Presentation is usually after 10 years of

age with

● ophthalmoplegia and ptosis,

● loss of facial expression and

● difficulty chewing.

● Generalised, especially proximal,

weakness may be seen.

Diagnosis

● improvement following the administration

of intravenous edrophonium ( less used

now)

● acetylcholine receptor antibodies (seen in

60–80%).

● EMG

Treatment

● Treatment is with the anti-muscarinic

drugs neostigmine or pyridostigmine.

● immunosuppressive therapy with

prednisolone or. azathioprine is of value.

● Plasma exchange is used for crises.

● Thymectomy :

is considered if a thymoma is present.

or if the response to medical therapy is

unsatisfactory.

Muscular Dystrophy

● Duchenne MD

● X-linked (only boys)

● Onset typically preschool age

● PROXIMAL muscle weakness –Gower sign +

● Face and eye weakness NOT present

● Pseudohypertrophy of calf (gastroc) muscles

● Toe walking

● Gait lordotic and wide based (waddling)

● Wheelchair bound by early-to-mid teens

● Progressive dilated cardiomyopathy eventually occurs

● Death by late teens to early 20s

▪ respiratory failure due to weakness, immobility and scoliosis

● Becker MD

● slowly progressive muscular dystrophy

● onset after preschool (elementary or later)

● prognosis more variable

● may live past middle age

● may self-ambulate without a wheelchair for may

decades

● progressive dilated cardiomyopathy occurs

● may result in end-stage cardiac failure

Pseudohypertrophy of

Calf muscles Gower Sign

● Diagnosis of both Duchenne vs. Becker MD: ● Elevated CPK (>10,000 DMD, < 10,000 BMD) ● Genetic mutation analysis*

▪ X-linked Xp21 ▪ Mutated Dystrophin gene product (in skeletal and

cardiac muscle) ▪ 2/3 symptomatic patients have positive genetic

mutation, 1/3 patients negative test ● Muscle biopsy - Dystrophin staining

▪ Dystrophin absent in Duchenne MD ▪ Dystrophin reduced in Becker MD ▪ Normal in all other muscle disorders

● Optimal management:

● Preserve ambulation with orthotics ● OT/PT to minimize contractures ● When non-ambulatory, prevention of scoliosis with:

▪ proper fitting wheelchair, spinal fusion if necessary

B. Infant Botulism (6 weeks – 6

months)

● Toxin of the bacteria clostridium botulinum

(which grows in the intestine) irreversibly binds

to the acetylcholine receptor at the NMJ

● Symptoms:

● poor feeding, poor suck, absent gag, weak cry

● descending paralysis, hypotonia, head lag

● reflexes reduced

● constipation

● respiratory compromise, apnea

Infant Botulism

● Source of C. botulinum spores

● Soil

● Foods

● honey

● corn syrups

● Diagnosis

● Isolation of organism or toxin in stool

● Treatment

● Botulism immune globulin (BIG)

Myotonic disorders

● Myotonia is delayed relaxation after

sustained muscle contraction. It can be

identified clinically and on electromyography.

Dystrophia myotonica

● dominantly inherited.

● nucleotide triplet repeat expansion,

● so this means there can be anticipation

through

Dystrophia myotonica

● Newborns:

● Mother:

● This manifests as slow release of handshake or

difficulty releasing the tightly clasped fist.

● Older children can present with myopathic facies

.learning difficulties and myotonia.

● Adults develop cataracts and males develop

baldness and testicular atrophy.

● Death is usually due to cardiomyopathy.

● Treatment considerations for SMAs:

● aggressive and early respiratory toilet

● assisted ventilation for most type 1 + many type 2

● physical therapy to avoid / minimize contractures

● encouragement of full educational pursuits– intellect

unaffected

● CNS MALFORMATIONS

Chiari Malformation:

low lying cerebellar tonsils

Dandy-Walker Malformation:

aplasia / hypoplasia of cerebellar vermis

(midline cerebellum missing or underdeveloped)

Dandy-Walker Malformation Ataxia due to aplasia of the

midline cerebellar vermis

Anencephaly

Occipital Encephalocele

Agenesis of Corpus Callosum in Aicardi syndrome

- only females

- seizures (inf spasms), MR / dev delay, microcephaly

- retinal lesions

- symptom onset 3-5 months

Lissencephaly: ―smooth brain‖

- achieve maximum 3-5 month dev milestones

- may be caused by LIS-1 gene mutation (Miller-Diecker

lissencephaly) - microcephaly, MR, seizures

Neurocutaneous Syndromes

● Neurofibromatosis

● Tuberous Sclerosis

● Sturge Weber

Neurocutaneous Syndromes

Neurofibromatosis

Tuberous Sclerosis

Sturge Weber

Neurofibromatosis

● Autosomal dominant

● NF 1

● 1:3500 incidence

● Mutation on chromosome 17

● NF 2

● 1:40,000 incidence

● Deafness (bilateral)

● CNS tumors

● Mutation on chromosome 22

Neurofibromatosis

● NF 1 criteria (need 2 of the following 9):

● + FHx ( but ~ ½ cases sporadic mutation)

● Skin criteria:

● CAL (need 6+, > 0.5 cm prepubertal, > 1.5 cm post-pubertal)

● Neurofibromas

● Inguinal / axillary freckling

● Bone criteria:

● Pseudarthrosis (angulation deformity of long bone)

● Scoliosis

● Hypoplasia of sphenoid bone in base of skull

● Eye criteria:

● Lisch nodules (hamartomas in the iris)

● Optic pallor (optic glioma)

Neurofibromatosis

● Autosomal dominant

● Two types:

● NF 1 (1:3500 incidence) NF 2 (1:40,000 incidence)

● chromosome 17 chromosome 22 (CNS tumors, deafness)

● mutation in Neurofibromin mutation in Merlin

● NF 1 criteria:

● + Family History ( but ~ ½ cases sporadic mutation)

● Skin

● CAL (need 6+, > 0.5 cm prepubertal, > 1.5 cm post-pubertal)

● neurofibromas

● Bone

● Pseudarthrosis (angulation deformity of long bone)

● Scoliosis

● Absence of sphenoid bone in base of skull

● Eye

● Lisch nodules (hamartomas in the iris)

● Optic pallor (optic glioma)

CAL

CAL

Neurofibroma

Axillary Freckling

Pseudarthrosis

Scoliosis

Sphenoid Bone

Hypoplasia

Lisch Nodules

Optic Glioma

Tuberous Sclerosis

● Autosomal dominant

● Chromosomes 9 and 16

● Skin hypopigmentations (―Ash leaf‖ spots)

● Benign hamartomas:

● skin

● adenoma sebaceum on face

● shagreen patch (brown leathery) on forehead or lower back

● brain, retina, heart, kidney

● Seizures in 80-90 %

Tuberous Sclerosis

● Autosomal dominant

● Chromosomes 9 (hamartin) and 16 (tuberin)

● Skin hypopigmentations (―Ash leaf‖ spots)

● Benign hamartomas:

● skin

● adenoma sebaceum on face

● shagreen patch (brown leathery) on forehead or

lower back

● brain, retina, heart, kidney

● Seizures in 80-90 %

Shagreen Patch

Adenoma

Sebaceum

―Ash Leaf‖

Spot

Cortical Tubers

Rhabdomyoma

Sturge Weber

● Unilateral port wine stain over upper face

● Buphthalmos (infantile glaucoma) 🡪

enlargement of globe, corneal clouding

● Intracranial leptomeningeal vascular anomaly

and calcifications in 90 %

● Seizures (partial / focal onset)

Port Wine Stain

Buphthalmos with enlarged

globe, corneal clouding

Leptomeningeal Vascular

Anomaly

The ‘floppy infant’

● picking up the infant, who tends to slip

through the fingers

● hang like a rag doll when suspended prone.

● There will be marked head lag when the

head is lifted by the arms from supine.

INFANTILE HYPOTONIA

● . Central hypotonia is associated with poor

truncal tone but preserved limb tone.

● Dysmorphic features suggest a genetic

cause.

● Lower motor neurone lesions are suggested

by a frog-like posture

● Neural tube defects and hydrocephalus

Neural tube defects

● failure of normal fusion of the neural plate to

form the neural tube during the first 28 days

following conception.

● Mothers of a fetus with a neural tube defect

have a 10-fold increase in risk of having a

second affected fetus.

Folic acid supplementation

● reduces this risk. High doses are now

recommended periconceptually for women

with a previously affected infant planning a

further pregnancy.

● Low-dose periconceptual folic acid

supplementation is recommended for all

pregnancies. In some countries e.g. United

States, folic acid is added to flour for bread.

Anencephaly

● This is failure of development of most of the

cranium and brain. Affected infants are

stillborn or die shortly afterbirth.

Encephalocele

● There is extrusion of brain and meninges

through a midline skull defect, which can be

corrected surgically. However, there are often

underlying associated cerebral malformations

Spina bifida occulta

● This failure of fusion of the vertebral arch

● incidental finding on X-ray,

● +\-overlying skin lesion such as a tuft of hair,

lipoma, birth mark or small dermal sinus.

usually in the lumbar region.

● There may be underlying tethering of the cord

(diastematomyelia).

● .Neurosurgical relief of tethering is usually

indicated.

Meningocele

● Meningoceles usually have a good prognosis

following surgical repair.

Myelomeningoceles:

● Variable paralysis of the legs •

● Sensory loss •

● Bladder denervation (neuropathic bladder) •

● Bowel denervation (neuropathic bowel) •

● Scoliosis

● Hydrocephalus from the Chiari malformation

(herniation of the cerebellar tonsils and

brainstem tissue through the foramen

magnum), leading to disruption of CSF flow.

Management –

● The back lesion is usually closed soon after

birth.

● physiotherapy helps prevent joint

contractures.

● For sensory loss – skin care is required to

avoid the development of skin damage and

ulcers.

● Neuropathic bladder – an indwelling or

intermitten catheter may be required for a

neurogenic bladder.

Hydrocephalus

● In hydrocephalus, there is obstruction to the

flow of cerebrospinal fluid, leading to

dilatation of the ventricular system proximal

to the site of obstruction.

● The obstruction may be within the ventricular

system or aqueduct (non-communicating or

obstructive hydrocephalus), or at the

arachnoid villi, the site of absorption of CSF

(communicating hydrocephalus)

clinical

Hydrocephalus In infants,

● increase in head circumference,

● separation of skull sutures,

● bulging of the anterior fontanelle,

● distension of scalp veins and

● sun setting of the eyes •

Older children present with raised intracranial

pressure •

―Sunsetting Eyes: clinical sign of

increased intracranial pressure