Epilepsy is a vast term, which encompasses a large variety of very different conditions. Epilepsy manifests itself by seizures that will be different according to which part of the brain is affected. Seizures are not synonymous with epilepsy. Some epileptic syndromes have several seizure types, and one seizure type can be seen in several different epileptic syndromes.

 

PAEDIATRIC SEIZURES

AND EPILEPTIC SYNDROMES

Dr. Lionel Traverse

SEIZURES can be classified between PARTIAL and GENERALIZED, PRIMARY and SECONDARY. Partial seizures can be either SIMPLE or COMPLEX, according to the absence or the presence of ALTERATION of consciousness. Generalized seizures are either ABSENCES, ATYPICAL ABSENCES, MYOCLONIC, CLONIC, TONIC, TONIC-CLONIC or ATONIC. Epileptic seizures and epileptic syndromes are two different concepts: one seizure type can be seen in several different syndromes

Single syndrome can have several different seizures types. (See appendices 1)

1.      The INTERNATIONAL CLASSIFICATION of EPILEPTIC SYNDROMES is based on 2 PILLARS:

The AETIOLOGY of the disorder and its LOCATION in the brain.

Epilepsies with GENERALIZED seizures vs. epilepsies with PARTIAL seizures; to which one has to add epilepsies UNDETERMINED whether FOCAL or GENERALIZED. Finally, there is a group called SPECIAL SYNDROMES, which is a wastebasket of heterogeneous disorders. Epilepsies with KNOWN AETIOLOGY: SYMPTOMATIC vs. epilepsies without aetiology: IDIOPATHIC; to which one has to add epilepsies which do not fit criterion for idiopathic but where no aetiology is found: These are CRYPTOGENIC. Unlike a disease, a SYNDROME does NOT necessarily have an unequivocal etiology and prognosis. On the other hand, some epileptic disorders included in this classification are in fact diseases, and for some others, currently considered as syndromes, a single aetiology may be discovered in the future. Unlike a disease, a SYNDROME does NOT necessarily have an unequivocal aetiology and prognosis. On the other hand, some epileptic disorders included in this classification are in fact diseases, and for some others, currently considered as syndromes, a single aetiology may be discovered in the future.

IDIOPATHIC EPILEPSIES, generalized or partial, have in common: a genetical predisposition, no morphological lesion, an age related onset and discharges of generalized Spikes and Waves (SW), even sometimes in idiopathic PARTIAL epilepsies.

In opposition to idiopathic epilepsies, the SYMPTOMATIC EPILEPSIES are a consequence of a known or presumed specific disorder of the central nervous system. The CRYPTOGENIC EPILEPSIES are assumed to be symptomatic, because they are definitely not idiopathic, yet no aetiology can be recognized

LOCALISATION RELATED EPILEPSIES are epileptic disorders in which seizure semiology or findings at investigations disclosed a LOCALISED origin to the epileptogenic area (structural or functional, but also patients with less well defined lesions whose seizures may originate from variable locations.

In idiopathic age-related epilepsies with focal seizures, the homologous regions of BOTH hemispheres may be functionally involved. In these childhood epilepsies, there are PARTIAL seizures and FOCAL EEG anomalies.

These epilepsies are AGE-RELATED.

There is NO DEMONSTRABLE ANATOMIC LESION.

They are subject to SPONTANEOUS REMISSION. In idiopathic partial epilepsies, there is no neurological or mental deficit, nor history of antecedent illness, but FREQUENTLY there is a family history of BENIGN EPILEPSY. The seizures are usually BRIEF AND RARE but occasionally at the onset of the illness, they can be frequent. There is usually a good therapeutic response to one single AED.

The seizure pattern may vary from one case to another but usually remains constant in the same child. If there is a post ictal-state, it is usually of SHORT DURATION. The DEVELOPMENTAL PROGNOSIS is good: there is no deficit in the neurological or psychomotor development.

On the other hand, in symptomatic localization-related epilepsies, the epileptogenic lesion can be traced to ONE part of ONE cerebral hemisphere. Imaging will demonstrate a focal lesion in most cases. The neurodevelopment and the epileptic prognosis depend on the underlying lesion. These epilepsies are usually difficult to treat and of poorer prognosis. SYMPTOMATIC PARTIAL EPILEPSIES are most certainly the most frequent epilepsies in adults, and the most frequent symptomatic epilepsies in children. They are the epilepsies related to a non-progressive encephalopathy e.g., trauma...

According to the International classification, GENERALIZED EPILEPSIES are disorders with generalized seizures, i.e.: seizures in which the FIRST clinical changes indicate involvement of BOTH HEMISPHERES. The ictal EEG patterns are initially bilateral.

There might be 2 reasons why seizures remain UNDETERMINED whether they are focal or generalized: the patient has both types of seizures together or in succession and has both focal and generalized EEG discharges; there are no positive signs of either focal or generalized seizure onset (the most common reasons for this are that the seizures occur during sleep or in the case of Neonatal seizures).

There are two types of SPECIAL SYNDROMES: when the seizures occur in a very specific context, or when the seizures occur in a very specific context, or when the seizure (or the episode of status epilepticus) is isolated.

II) NEONATAL EPILEPTIC SYNDROMES, by definition should occur within 4 weeks of birth but in fact often very early, or may even have their onset after the end of the first month.

NEONATAL SEIZURES are probably very frequent and present unique considerations due to the immaturity of the newborn brain. These seizures are often very subtle and unrecognized. They may include tonic horizontal deviation of the eyes with or without ocular or palpebral jerks, lip smacking or other bucco-lingual movements, swimming or pedaling movements, and occasionally apneic seizures. In the premature infant particularly, tonic extension of the limbs mimicking decerebration or decortications has been described. Several types of seizures have been described amongst which tonic and myoclonic ones carry a poorer prognosis.

Two particular NEONATAL EPILEPTIC SYNDROMES deserve special attention. BENIGN FAMILIAL NEONATAL CONVULSIONS are transmitted on the autosomal dominant mode. Tonic or apnoeic seizures usually occur on the 2nd or 3rd day of life. These children have a 14% chance of developing epilepsy later in life. BENIGN IDIOPATHIC NEONATAL CONVULSIONS have their onset later: on the 5th day of life. Seizures are frequent and at times, the child will present in status epilepticus. However, the prognosis is usually very good with no neurodevelopmental or epileptic sequelae. There are a couple of other neonatal syndromes: the Aicardi and the Ohtahara syndromes, which are very rare and carry a very poor prognosis.

III) INFANTILE EPILEPTIC SYNDROMES have their onset in the first 5 to 6 years of life. Except for Febrile convulsions, these syndromes are usually of poor prognosis.

The WEST SYNDROME consists of a triad:

-INFANTILE SPASMS are epileptic spasms occurring during infancy. Spasms are usually due to sudden contraction of the flexor muscles giving the classical “Salaam jerk”. The spasms can be in extension, lightning, unilateral etc... However, most often they are mixed. The onset is usually between 4 and 7 months sometimes earlier, but never after 1 year. The prognosis has improved with the use of new anticonvulsive medications.

-ARREST IN PSYCHOMOTOR DEVELOPMENT is a constant feature although at times this is not immediately noticeable. The outcome is usually poor but is better (25 to 50% normal or borderline mental retardation) in the cryptogenic group, compared to the symptomatic group, as in TS, with only 10% favorable outcome.

-HYPSARRHYTHMIA is a specific EEG tracing.

The LENNOX-GASTAUT SYNDROME associates:

-DELAYED PSYCHOMOTOR DEVELOPMENT leading to mental retardation, usually in a child who is already affected by an encephalopathy of some kind (60%),

-SEIZURES of various types usually axial tonic, atonic drop attacks, atypical absences; other seizures are frequently observed: myoclonic (head drops or massive jerks), GTCS, partial (simple and more often complex), slow-sleep induced seizures will often interfere with the ability to fall asleep. Frequently the child will progress to status epilepticus.

-Specific EEG pattern with very abnormal background, diffuse slow (< 3 Hz) SW, frequent multi focal (mostly frontal and temporal) anomalies during sleep with burst of fast rhythm (at 10 Hz). The prognosis is invariably poor.

BENIGN MYOCLONIC EPILEPSY occurs in an otherwise normal infant: onset in the second year of life of generalized myoclonic fits at high frequency. No other seizure types are noted and the treatment is usually easy with one anticonvulsant. The EEG is not very specific and exacerbated during sleep. The outcome is usually good, but for the occasional patient who will develop GTCS and/or mild developmental delay.

In contrast, SEVERE MYOCLONIC EPILEPSY OF INFANCY is associated with a poor outcome in the majority of cases. In the first year of life, the child will often present with atypical febrile seizures. Then between the end of the 1st year and the 4th birthday myoclonic jerks appear. The child progresses to having partial seizures as well as atypical absences. Treatment is very difficult and disappointing. Neurological outcome is poor.

MYOCLONIC-ASTATIC EPILEPSY or DOOSE SYNDROME resembles the Lennox-Gastaut Syndrome in almost all respects but for the EEG. The seizures are however more astatic with predominance of drop attacks over the other seizure types. Some question the reality of this entity.

Finally, in the preschooler the most frequent seizures are the so-called "FEBRILE SEIZURES". These are generalized seizures occurring between 6 months and 6 years of age, immediately generalized, short lasting (less than 5 minutes), associated with fever, in an otherwise healthy child. If anyone of these criteria is absent, then the seizure becomes an atypical febrile seizure and investigations should be entertained. As a simple rule of thumb, any child who arrives in ER convulsing can be considered as atypical, since this implies that the seizure lasted too long. Simple febrile seizures: do not need to be treated.

IV) CHILDHOOD EPILEPTIC SYNDROMES can be defined as having their onset on the prepubertal school-aged child. They are usually idiopathic epilepsies with good prognosis.

CHILDHOOD ABSENCE EPILEPSY classically occurs in a 6-year-old girl with a strong family history of epilepsy. A TYPICAL ABSENCE is of SHORT DURATION (less than 10 to 15 seconds) in 75% of cases. Onset and termination are ABRUPT. Patient resumes his or her activity where it had been interrupted. Occasionally a brief RETROGRADE AMNESIA can be seen. A stimulus can shorten the absence. The loss of contact can be PARTIAL. The child remains motionless, eyes vacant, staring straight or drifting upwards. Respiration may slow down if the absence lasts longer. Eyelids FLICKERING are seen in 50% of typical absences, NEVER in atypical absences.

If absence happens while eyes are closed, they will always open spontaneously within 2 to 5 seconds. There is retropulsion in 25% and GTCS on awakening in 2/3 of cases. One can distinguish 6 types of absences:-with mild clonic component 50%, often eyelids flickering, -with atonic component 20%, gradual lowering of the head due to decrease tone rather than complete atonic, -simple absence 10%, -with tonic component 25%, upward deviation of the eyes, -with automatisms frequent, either de novo or preservative, -rare with autonomic component. (See appendices 2)

EPILEPSY WITH MYOCLONIC ABSENCES is a rare syndrome, which carries a much poorer prognosis.

On the other hand, ROLANDIC EPILEPSY is much more frequent (the most frequent idiopathic partial epilepsy). The diagnosis is often easy, but when the seizures are nocturnal and secondary generalized, it may be more difficult. The seizure typically involves the hemiface with a short motor or sensory-motor component. The partial clonic seizure may spread to the shoulder arm or even the hemibody. The EEG is classical but not pathognomonic. The evolution is invariably good.

CHILDHOOD EPILEPSY WITH OQCIPITAL PAROXYSMS is the equivalent of the Rolandic epilepsy for the occipital lobe. Of course, the seizures are different since originating from the occipital lobe. They are VISUAL and often followed or accompanied by migraine headache. The prognosis is not as favourable as for the Rolandic Epilepsy.

BENIGN FRONTAL LOBE EPILEPSY, BENIGN PSYCHOMOTOR EPILEPSY, BENIGN EPILEPSY WITH GIANT SOMATOSENSORY POTENTIALS, THE LANDAU- KLEFFNER SYNDROME and EPILEPSY WITH CONTINUOUS SPIKES WAVES DURING SLOW-SLEEP are extremely rare.

V) JUVENILE EPILEPTIC SYNDROMES are rarer and usually of good outcome.

JUVENILE ABSENCE EPILEPSY is very similar to Childhood absence epilepsy but for a higher frequency of GTCS and a pharmaco-dependency. The EEG is slightly different.

JUVENILE MYOCLONIC EPILEPSY described by Janks, is often unrecognized until the first generalized TCS. On awakening the teenager shows partial myoclonic jerks which he or she will try to include in a movement. It responds well to treatment but is often pharmaco-dependent.

EPILEPSY GRAND MAL ON AWAKENING is thought to be a form of JME and is likely going to be abandoned as a specific entity.

PRIMARY READING EPILEPSY, PURE PHOTOSENSITIVE EPILEPSY, and other EPILEPSIES WITH SPECIFIC TRIGGERS are very rare. Only about 1% of all epilepsies are photosensitive.

 

VI) TREATMENT

One must distinguish between treatment of the SEIZURE and treatment of the EPILEPSY.

1. TREATMENT OF THE SEIZURES.

Basically any seizure lasting more than 5 minutes should be stopped. This in fact means that any child seen in an emergency room with seizure on arrival should be treated since it is almost impossible to reach an emergency room in less than 10 to 15 minutes even if the child lives just beside a hospital.

To stop a seizure, the drug of choice remains DIAZEPAM. In small children, the easiest route of administration is the rectal route. In older patients one prefers the IV route.

 

INITIAL TREATMENT OF SE

The outcome of SE is primarily related to the underlying cause of the SE.

 

2. TREATMENT OF THE EPILEPSY

The classical approach to treatment of the epilepsies is based on the principal seizure types encountered in a given syndrome. Primarily generalized epilepsies are usually treated with Valproic Acid. Ethosuximide, phenytoin and phenobarbital are much less frequently used since the introduction of the new AED's such as Lamotrigine, Topiramate, and Vigabatrin. Clobazam has been found to be as effective as phenytoin or clobazam in monotherapy of generalized, tonic-clonic seizures. The drugs recommended in partial in epilepsies include tegretol, dilantin and depakene. But again drugs such as frisium are as effective in monotherapy.

With such choices, 65% of patients are well controlled in monotherapy. Another 10% will be controlled with the addition of a second anticonvursant. Finally another 5% will be controlled with a third or a fourth AED. At the end about 20% of the patients have intractable seizures.

With regard to the choice of the first AED, it seems that almost any drug will do. Phenytoin, Carbamazepine Valproate or clobazam have equal efficacy.

The ideal new AED would be effective against all seizure types, have no side effects, no drug interactions, be administered twice daily and be inexpensive.

 

The drugs effective in epilepsies are:

1. CARBAMAZEPINE. It is the drug of choice for partial epilepsies. Well tolerated, the side effects are uncommon but it interferes with many other medications, in particular erythromycin. The main side effects are:

Allergic skin reactions

Liver dysfunction or decreased haemoglobin and/or platelets

SLE, hypothyroidism electrolytes imbalance

Teratogenicity

May worsen some seizure types, in particular myoclonic seibzures.

The dose is up to 24 mg/Kg per day. Usually a dose between 10 and 15 mg/Kg/day is enough. One starts at a low dose such as 2 to 5 mg/Kg/day and increases gradually at 1 week to 10 days intervals. It is available in chewable tabs and a CR preparation allows BID dosages.

 

2. CLOBAZAM. Is a 1,5-benzodiazepine (the others are 1,4- benzodiazepines) and is given at the dose of 0.5 to 2 mg/Kg/day. It should be started slowly. Clobazam is less sedative than the other benzodiazepines, but has all the other side effects and at times children may become aggressive.

 

3. VIGABATRIN is an excellent medication. It has very few side effects, the most frequent being increased secretion and weight gain. It is very well tolerated even at very high doses. The usual doses are about 80 mg/Kg/day. It irreversibly inhibits GABA reabsorption.

4.VALPROATE is one of the best drugs we have for generalized epilepsy. Hepatic toxicity is very rare and usually in young children <2 y-o> with severe epilepsy and multiple drugs treatment. Tremor is a frequent problem but it is dose-related and diminution in the dosage usually resolves the problem. It is teratogenic.

The rage of dosages is fairly wide (15 to 60) allowing for lots of manipulations. Again one would start at a lower dose such as 5 to 10 per kilo and then slowly increase.

 

5. PHENYTOIN remains widely used in spite of its high incidence of side effects. Acutely one may see nystagamus, ataxia, rash, stupor, and sedation. Chronic side effects include gum hyperplasia and hirsutism, increased seizures frequency megaloblastic anaemia. It is teratogenic. Maintenance dose is 4 to 7 mg/Kg/day.

 

6. TOPIRAMATE is going to make a major impact in epilepsy management. It is given at 8 mg/Kg/day in children and is a very efficient anticonvulsant. TThe side effects are not frequent and usually mild. Slowing of mentation is similar to all other AED’ s and can be avoided by starting slowly. Hyperactivity can be a major problem. It is often associated with weight loss. Renal stones have been reported particularly when the medication is started too fast.

 

7. PHENOBARBITAL is usually in a variety of generalized seizures in spite of its various side effects. It is particularly used in the neonatal periode, in the prophylaxis of febrile seizures and in the management of drop attacks. Side effects are slowing of the mentation, but also often hyperactivity in the younger child. It has been shown to decrease the ultimate IQ by few points. It is given at the maintenance dose of 3 to 5 mg/Kg/day.

 

Appendice 1

 

I PARTIAL SEIZURES

 

A. SIMPLE PARTIAL SEIZURES

There is no alteration of consciousness. They usually have

unilateral hemisphere involvement.

1. With MOTOR SIGNS. Focal motor seizures may remain strictly focal or may spread to contiguous areas (epileptic march). The seizure is then known as a Jacksonian seizure. They can be versive with head turning to one side (usually opposite to the discharge). They may be associated with palilalia (involuntary repetition of a syllable or phrase).

2. With SOMATOSENSORY or SPECIAL SENSORY symptoms.

a. Somatosensory: pins and needles feeling. May spread or evolve toward complex partial and/or generalized.

b. Visual: simple flashing or more elaborated hallucinations.

c. Auditory: simple or music.

d. Olfactory: usually unpleasant.

e. Gustatory: pleasant or odious, metallic.

f. Vertiginous symptoms, sensation of falling or floating or _LJ vertigo.

3. With AUTONOMIC symptoms such as vomiting, pallor tachycardia etc.

4. With PSYCHIC symptoms. (although they usually occur with impairment of consciousness ie: complex partial seizures)

a. Dysphasia

b. Dysmnesic: distorted memory such as deja-vu or jamais-vu, deja-entendu or jamais-entendu, or even forced thinking and panoramic vision (rapid recollection of episodes from past life) c. Cognitive disturbances Dreamy state.

d. Affective symptomatology: extreme pleasure or displeasure, fear Gelastic (laughing seizure) should not really be classified as affective since the laughter is usually without affect.

e. Illusion, such as monocular diplopia, distortion of size etc...

f. Hallucinations can be visual, auditory olfactory and very elaborated.

B. COMPLEX PARTIAL SEIZURES

They are usually initially unilateral but then will involve both hemisphereses, and there is "impairment of consciousness.

The hallmark is the gradual increase in the impairment of consciousness.

The beginning and end is not "as" abrupt"as in abscences. They are divided into temporal and extra temporal. Temporal type usually starts "with an empty stare with clouding followed by automatisms,oral, mimic or verbal automatisms with semipurposeful character. The extratemporal is usually temporal with aversion and rotation of the body.