SEIZURES IN CHILDHOOD

Kindu Woldemichael, MD

Seizure (Sz)• Defn: paroxysmal, time-limited change in motor

activity and/or behavior that results from abnormal electrical activity in the brain.

• Common, occur in ~10% of children, - most are provoked by somatic disorder

originating outside the brain: high fever, infection, hypoxia, toxins, arrhythmias, or electrolyte abnormalities (Na+, Ca++);

- may also signal serious systemic/ CNS problem.

Epilepsy • A condition in which Sz is triggered recurrently from

within the brain without obvious precipitants. • for epidemiologic purposes- it is defined as two or

more unprovoked Sz occurring at an interval of >24 hr apart.

• not a specific disease, but a condition arising from variety of pathological insults involving the cerebral cortex.

Evaluation of the first Sz• In the Hx-• look for features suggesting

– meningitis,– sepsis, – head trauma, – ingestion of drugs, toxins;

• details of pregnancy & delivery; [perinatal asphyxia]

• detailed description of the Sz type:– focal/generalized,– duration, – consciousness,– sensory/motor (if motor: tonic, tonic-clonic,

clonic, myoclonic, spasm, atonic, etc), – posture of the patient, loss of sphincter control

• preceding aura (epigastric discomfort ,pain)

Cont’d…• On examination- - ABC, - Temperature, BP - HC, length/ ht, Wt - papiledema, retinal hemorrhage, - focal signs- subtle hemiparesis/ hyperreflexia,

Cont’d

- cutaneous signs of neurocutaneous syndromes vitiligo of Tuberous Sclerosis(TS), shagreen patch of TS),café-au-lait spots of NF-1,nevus flammeus of Sturge -Weber syndrome).

• Investigations- depending on suspected cause.

port-wine stains

Hypomelanotic macules (ash leaf spots) on the thorax of a child with tuberous sclerosis

Skin-colored and pink-tan, soft papules & nodules on the back- neurofibromata

Shagreen patch on back of patrient with tuberous sclerosis

Unprovoked Sz• First Sz - potential family hx of epilepsy, - prior neurologic disorder, - hx of Sz with fever, - LP- has limited value, - EEG- recommended

- for Dx of event, - prediction of recurrence risk, - for Dx of focal abnormality.

Cont’d- Neuroimaging- generally not recommended unless

neurological examinations indicate a possible abnormality.

- anticonvulsants: not recommended for only one Sz.

• Recurrent Sz - epileptic with risk of recurrence, - type of Sz, frequency, precipitating factors (1st

convulsion may be with a viral illness), - behavioral abnormalities before several days,

Cont’d- prolonged personality change/ intellectual

deterioration (degenerative CNS disease), - vomiting, failure to thrive (structural lesion),- hx of previous Rx, drugs that potentiate Sz.

On examination- - neurologic, ophthalmologic & general exam, - ↑ ICP, neuro-cutaneous synd., structural brain

abnormalities ( injuries, malformations, infections, tumors).

Cont’d- EEG, . EEG can be abnormal in 3-5% of normal children.- serum electrolyte( Mg, Ca, Na),- LP (occasionally- chronic infection, metabolic abn.)- Neuroimaging- - esp. for those with neurological deficits or partial Sz,

or focal neurological abn.)- MRI- more sensitive than CT for detecting brain

malformations & dysplastic lesions.

Etiology - Any insult to the cerebral cortex can cause Sz,- Typically arise from the neocortical gray matter & the

limbic system, some may arise from subcortical regions.

- Idiopathic/cryptogenic, - vascular, - traumatic, - developmental, - infectious, - neoplastic, & - degenerative causes respectively are among the common

causes.

International Classification of Epileptic Sz (Based on Hx & EEG)

• Partial Sz: - Simple partial (consciousness retained) . motor, sensory, autonomic, psychic

- Complex partial (consciousness impaired) . Simple partial, followed by impaired consciousness . Consciousness impaired at onset

- Partial Sz with secondary generalization

Classification cont’d

• Generalized Sz - Absences- typical, atypical - Generalized tonic-clonic, tonic, clonic - Myoclonic - Atonic - Infantile spasms

• Unclassified Sz

[myoclonus]

[infantile spasm]

[frontal lobe epilepsy]

[geliastic]

[automatism]

[atonic seizure]

[atonic]

Epilepsy syndromes• Using age of onset, cognitive development,

neurological exam, Sz type & EEG findings;• Syndromic classification enables appropriate Mx

(including surgery) & Px;• Examples : - Infantile spasms, - Benign myoclonic epilepsy of infancy, - Lennox- Gastaut syndrome, - Rolandic epilepsy of childhood,

Partial Sz -Most common Sz type in all age groups, >50% of all Sz in children;

• Simple partial Sz (SPS)– motor activity most common, clonic/tonic, involve face,

neck, & extremities,– no automatism, – some may have aura,– average duration- 10-20 sec,– conscious,– no post-ictal event.

DDx- tics (but these can be suppressed) - EEG- spikes/sharp waves uni-/bi/ multifocal.

• Complex partial Sz (CPS)

• may begin with SPS. • aura is present in 1/3• Aura always indicates a focal source of seizure• Loss of consciousness may coincide with onset or

proceed after seizure.• brief blank stare, sudden pause• period of impaired consciousness brief & few,• automatism common (50-75% of cases), develop

AFTER loss of consciousness & may persist into the post-ictal state: include lip smacking, chewing, & swallowing.

Cont’dIn older children- picking & pulling at clothes,

walking/running- nondirective, repetitive; - CPS can result in 2º generalization, - duration average 1-2min, - EEG- anterior temporal lobe sharp waves/ focal

spikes, & multifocal spikes; - CT & MRI- abnormality in the temporal lobe

sclerosis, hamartoma, gliosis, glioma, AVMs.

Generalized Sz Absence Sz: Simple (typical) absence (Petit mal)- Sudden cessation of motor activity or speech with a

blank facial expression & flickering of the eyelids, no loss of body tone,

- uncommon before 5 yr of age; girls>boys;- usually <30sec, no aura / post-ictal state,- countless Sz daily, automatism frequent,- Hyperventilation for 3-4 min produces it.- EEG- Typical 3/sec spike & generalized wave discharge

DDx- CPS (few in #, aura, postictal state, motor signs)

• Generalized Tonic-Clonic Sz (Grand mal)

- most common generalized Sz, may follow a partial Sz or occur de novo;

- may be ass’ed with aura (focal origin);

- duration- few minutes;

- loss of consciousness, eyes roll back, tonic contraction, clonic movements, & loss of bladder control, ± cyanosis, apnea.

- Post ictally semi comatose & then deep sleep from 30min to 2 hr.

• Myoclonic Epilepsies of Childhood - repetitive Sz consisting of brief, often symmetric

muscular contractions, loss of body tone & falling/slumping forward

- 5 distinct sub groupings:Benign Myoclonus of InfancyTypical Myoclonic Epilepsy of early childhoodComplex Myoclonic Epilepsies (Lennox-Gastaut)Juvenile Myoclonic EpilepsyProgressive Myoclonic Epilepsies

• Infantile Spasms - begin between 4-8 mo of age; - brief, symmetric, contractions of the neck, trunk, and

extremities; - 3 types: flexor, extensor, & mixed[most common]; Flexor- sudden flexion of neck, arms, & legs,Extensor- extension of the trunk & extremities,Mixed- most common.

Cont’d

- a cry may precede or follow - occur during sleep/arousal, usu. awake - EEG- hypsarrhythmia – bilateral - classified as cryptogenic & symptomatic. * In the symptomatic pts. many pre-, peri-, & post natal

factors: Hypoxic-Ischemic Encephalopathy (HIE), IntraVentricular Hemorrhage (IVH), PeriVentricular Leukomalacia (PVL), Cong. infections, neurocutaneous synd., CNS infections precede the spasms;

80-90% risk of MR.

Pathogenesis of infantile spasms- several theories

- dysf’n of the monoaminergic neurotransmitter system in

the brainstem; - derangement of neuronal structure in the brainstem; - abnormal immune system; - CRH- [corticotropin releasing] stress/injury to infant during a critical period of

neurodevelopment, CRH overproduction neuronal hyper excitability & Sz. (exogenous ACTH & steroids used in Rx)

Febrile Seizures• Most common Sz disorder in childhood;• Age dependent- common b/n 9mo-5y, peak age~14-

18mo;• Incidence- 3-4% of young children;• Possible genetic predisposition;• Generally-excellent prognosis, but may also signify

serious underlying infection, e.g. meningitis;• Usu. generalized tonic clonic, rarely focal;

Clinical manifestations• Core temp. ≥ 39 ºC;• Generalized tonic-clonic Sz, few sec. to 10min;

• Atypical – duration >15 min, repeated Sz within the same day, focal Sz/ findings;

• ~30-50% have recurrence with later fever;

• Generally no greater risk of later epilepsy, but some factors are associated with ↑ risk:

Cont’d - atypical, family history, 1st episode at < 9mo, - delayed developmental milestones, - preexisting neurological abnormality,These factors ↑ the risk to ~9% (Vs 1%).• Determine the cause of fever & R/o meningitis, - Viral infections of the URT, AOM, tonsillitis.

Lab. - RBS, LP esp. if 1st episode and in infants, - Other inv. depending on the presentation.

Rx of febrile convulsion• ABCs,• Arrest convulsion using diazepam,• Careful search for the cause of the fever,• Control the fever- paracetamol & sponging;• Antiepileptics - have no effect,• Reassurance of parents- excellent Px, - fever control at home, - possible recurrence with febrile episodes, - goes away by 5-6 yr of age.

Cont’d…

Mechanisms of Sz- - precise mechanism unknown.• Needs neurons generating significant burst discharge

& GABAnergic inhibitory system, • Excitatory amino acid neurotransmitters produce

neuronal excitation on specific receptors.• Underdeveloped brain (young age) more susceptible.

Cont’d

• Sz may arise from areas of neuronal death, abnormal tissue (tumors, AVMs, gliosis).

• Genetic factors- ~20% of all epilepsies.

Use of the EEG to Dx epilepsy

• paroxysmal discharges during Sz- diagnostic,• the interictal EEG normal in ~40% of cases.

• hyperventilation, eye closure, phototic stimulation, sleep deprivation- ↑ positivity

Rx of Epilepsy• 1st step- ensure that the patient has a Sz

disorder and not pseudoseizures,

NON-EPILEPTIC EVENTS Vs EPILEPTIC

• Generalized motor seizures cannot be interrupted by vocal or tactile/painful stimulation, with pseudoseizures sudden return to normal after a painful stimulus,

• An abrupt return of consciousness and subsequent loss of consciousness is more typical of a pseudoseizure.

• Waxing & waning of clonic/ tonic activity or stimulus-provoked clonic/tonic activity during a generalized motor seizure a pseudoseizure.

• A sudden loss of tone in a neurologically normal individual with protective behavior (i.e., outstretched arms) is suggestive of a non epileptic seizure;

• If the patient keeps the eyes tightly closed during the seizure and if passive opening is actively resisted pseudoseizure;

• An abrupt return of normal alertness (i.e., no postictal state) after a generalized motor seizure or prolonged loss of consciousness is unusual in a true seizure.

• A patient with pseudoseizures will often avoid painful stimuli or, if "unconscious," manifest a positive "arm on face" maneuver, where an apparently flaccid arm avoids hitting the face when dropped from above the face.

Rx of Epilepsy….- 1st afebrile convulsion, healthy child, no family hx, normal

examination & EEG- Do not treat!!

• 2nd step- choosing an anticonvulsant when indicated. Depends on type of the Sz.

- Goal: use only one drug with few side effects, : dose ↑ slowly until Sz control.• Benzodiazepines – e.g. diazepam, lorazepam. - initial Rx of status epilepticus, - may cause CNS depression esp. with other CNS depressant drugs.

Mechanisms of Action of AED• AED appear to act primarily by blocking the

initiation or spread of seizures. The mechanisms include:

- inhibition of Na-dependent AP in frequency-dependent manner (e.g., phenytoin, carbamazepine, lamotrigine, topiramate, zonisamide,)

- inhibition of voltage-gated Ca2+ channels (phenytoin),

- decrease of glutamate release (lamotrigine), - potentiation of GABA receptor function

(benzodiazepines and barbiturates), - ↑ in the availability of GABA (valproic acid,

gabapentin, tiagabine), - ethosuximide and valproic acid, probably act

by inhibiting T-type Ca2+ channels in thalamic neurons.

• Carbamazepine: - Rx of grand mal & partial Sz.

- plasma conc. decreased by phenytoin, phenobarbital, & valproic acid,

- leukopenia & hepatotoxicity can occur in the 1st 3-4 mo. Do CBC, SGOT & SGPT.

• Ethosuximide - Rx of typical absence Sz.

• Phenobarbital - Rx of grand mal Sz.

Cont’d

~25% of patients can have behavioral abnormality, may affect cognitive performance.

• Phenytoin - generalized tonic-clonic (primary & secondary),

partial, status epilepticus.

• Valproic acid- - broad spectrum & used in the Rx of grand mal Sz,

absence Sz, atypical absence, & myoclonus.

Cont’d

• If complete Sz control, a minimum of 2-sz- free years is a safe period of Rx in those with no risk factors.

• risk factors: – age >12yr at onset,– neurologic abnormality,– prior neonatal Sz,– many Sz before control.