Documente Academic
Documente Profesional
Documente Cultură
Francis M. Filloux, MD
rev: 8-21-02
OBJECTIVES
1. Understand the definitions of seizure, epilepsy, and other terms related to this topic.
2. Discuss the demography/epidemiology of seizures and epilepsy.
3. Understand the different types of seizures:
A. Recognize the key features distinguishing partial from generalized
seizures
B. Understand how these differences impact choice of treatment.
4. Recognize the cardinal of features of key epileptic syndromes.
5. Understand the diagnostic approach to seizures.
6. Understand the basics of treatment of epilepsy.
Seizures represent the most common neurologic disturbance affecting humans other than
headache (which you could argue is often not really neurological). Up to almost 10% of
the population will experience at least one seizure in their lifespan. Of these, nearly half
will be subject to recurrent seizures (epilepsy). Seizures and epilepsy are particularly
troublesome for patients because of their unpredictable occurrence and the associated
abrupt loss of competence. This often results in severe social and personal morbidity
with attendant loss of self confidence, personal safety, financial and recreational
independence. Treatment, however, is generally very successful and promising new
modalities of treatment are rapidly being developed or refined.
I. Definitions:
Seizure: (from Gk, to be seized from forces without) generally refers to a
disturbance of usual neurological functioning of relatively abrupt onset that is due to
transient disturbance of CNS activity. Other more or less synonymous terms include:
attack, fit, spell.
Epileptic seizure: a seizure caused by recurrent, sudden, synchronous (paroxysmal)
firing of a group of cortical neurons; in other words, a seizure due to a paroxysmal
electrical disturbance of brain signaling.
Epilepsy: condition in which an individual suffers from recurrent epileptic seizures
which is not temporary.
Convulsion: The overt, major motor manifestations of a seizure (rhythmic jerking of
the limbs).
Aura: subjective disturbance of perception that represents the start of certain seizures
(actually represents a focal electrical disturbance at the start of the seizure).
Ictus or ictal phase: the seizure itself; the part of the event where the convulsion
occurs or when the brain activity consists of paroxysmal firing of brain neurons.
Post-ictal phase: the period after the convulsion or actual seizure where the brain is
tired and the individual is sleepy, confused, disoriented or experiences temporary
neurological dysfunction.
Interictal: between seizures.
II. Background:
About 1-2% prevalence of seizure disorders in the US.
Cumulative lifetime incidence of epilepsy is about 3-4%; Cumulative lifetime incidence
of a seizure is about 9%.
Onset of epilepsy is most common in the young (children) and the elderly.
About 40% of epileptics have a generalized epilepsy syndrome (see below)
About 50 % of children have a generalized epilepsy syndrome compared to about 20 %
of adults.
III.
abnormality or identified disease (such as infection). Many idiopathic cases are familial,
and may be related to gene defects (e.g., such as BFNC as noted above). Many idiopathic
cases are relatively benign, self-limited and occur more often in children.
Secondary (symptomatic): caused by a brain disease, injury, focal disturbance etc... For
example, brain infections, tumors, scarring from strokes, drugs, etc...
Overall, cause of seizure disorders is unknown (idiopathic) in about 70% of cases;
Proportion of idiopathic cases is highest in middle-aged children (5-12) and lowest in
neonates and adults over 20.
V. Classification Scheme of Seizures/Epilepsy (see figure)
A. THE SEIZURE IS THE SYMPTOM; EPILEPSY IS THE DISEASE. Seems
confusing?!? Just remember then: the seizure is what you see or what the family,
patient, police officer, EMT etc.. tells you they saw. The epilepsy syndrome is what
you as a physician diagnose (if you can)
Example: child aged 6 has recurrent, early morning convulsions before awakening
observed by the parents (these are the seizures). There is a history of similar events in
other children. After evaluation, you find the EEG abnormality is typical. You
diagnose Benign Rolandic Epilepsy (this is the disease or epilepsy syndrome). From
this epilepsy diagnosis alone you can reassure the family about prognosis and provide
appropriate advice and treatment!
B. A Simpletons Seizure Classification: see figure:
1. Generalized vs. Partial
a. Generalized:
The whole brain is affected at once; both hemispheres electrically
disturbed.
The key (essential) clinical feature is LOSS OF CONSCIOUSNESS!
b. Partial (focal):
Only part of the brain (the focus) is affected.
Consciousness is not lost (in some it can be impaired... see below)
The only tricky part is that a seizure can start as a partial (focal) seizure and
spread (generalize). This is known as the process of secondary
generalization. If you are not able to observe or otherwise define the onset of
a given generalized seizure, you may not be able to tell if it is a primary
2. Complex partial (appropriately, given their name, these are the most
complicated seizures to understand, so bear with me and hang in there!!!)
again, only one part of one hemisphere of the cerebral cortex affected
initially.
However, there is greater spread of the discharge to allow impairment of
consciousness
Hence, there is ALTERATION of consciousness during part of the seizure
The seizure often starts as a focal seizure (if this affects perception, this is
known as an aura).
Spread or extension of the discharge results in alteration of consciousness
Normal behavior is affected and patients often manifest automatisms: lipsmacking movements, fumbling, non-sensical hand movements, fidgeting,
stereoptypic repetitive behaviors, or even fairly complex patterns of nonwilled, non-sensical behavior. Some functional interaction with the
environment is often possible.
Duration is usually more than 30 seconds; can last many minutes.
There is post-ictal confusion, disorientation or fatigue and sometimes
agitation or combativeness. Amnesia for some portion of the ictus occurs.
If there is sufficient spread (generalization), there can be secondary
generalization to a generalized tonic-clonic convulsion.
Other important considerations regarding Complex-partial seizures:
Often referred to as psychomotor seizures because of the prominent
disturbance of psychological or behavioral function
Also often referred to as Temporal lobe seizures due to the frequent
origin in the mesial (medial) temporal lobes or posterior frontal lobes.
Due to the proximity of the discharge to medial temporal lobes and
olfactory pathways the aura often consists of an olfactory hallucination,
fleeting memory percept, or other ineffable sensation (often a rising
epigastric sensation)
There is often a significant overlap with psychiatric disturbances (both in
terms of clinical manifestations of the seizures as well as with inter-ictal
behavioral function)
So, to remember the key elements of complex-partial seizures,
remember the 4 As
Aura
Alteration of consciousness
Automatisms
Amnesia
the transitions between wakefulness and sleep. usually affect oral-motor function
particularly. infrequent (weekly or less)
Etiology: unknown (idiopathic). often familial. presumed ion channel?
Age: childhood (5-12years)
EEG: focal, centrotemporal (Rolandic) spikes (i.e., located over the rolandic
cortex... yes, you got it, where the sensory-motor strip is found)
Treatment: no treatment or carbamazepine.
Prognosis: excellent. easy seizure control. remission in 95%. no long term
sequellae.
***B. Childhood absence epilepsy. The next most common seizure disorder of
childhood.
Seizure type: simple absence seizures. 1/3 or less will also have at least one
generalized tonic-clonic seizure. Often frequent (many per day).
Etiology: unknown (idiopathic). often familial. presumed ion channel?
Age: childhood (5-12years)
EEG: generalized 3/sec spike and wave discharges.
Treatment: ethosuximide or valproic acid.
Prognosis: excellent. easy seizure control. remission in 70% or more. few with
long term sequellae.
C. Idiopathic Generalized tonic-clonic epilepsy. More variable and later onset.
Seizure type: generalized tonic-clonic seizures. Often in early AM or after nap. No
warning, or non-specific feeling before seizure hits.
Etiology: unknown (idiopathic).
Age: later childhood, early adulthood: 10-25 years
EEG: normal or generalized less well defined spike and wave discharges.
Treatment: carbamazepine, valproic acid or phenytoin.
Prognosis: good. fairly easy seizure control in about 75%. remission more variable
than the above.
D. Juvenile myoclonic epilepsy. A rarer syndrome with onset in adolescence.
Seizure type: early morning myoclonic seizures (single or multiple myoclonic jerks).
absence seizures. generalized tonic-clonic seizures.
Etiology: unknown (idiopathic). often familial. presumed ion channel?
Age: childhood (10-16years); female predominance.
EEG: generalized fast spike and wave discharges (4 to 6 cycles/sec) often with
photosensitivity.
Treatment: valproic acid.
Prognosis: generally excellent seizure control possible but remission is rare.
***E. West syndrome (infantile spasms). The most typical recognizable specific
pattern of infancy. Represents a specific seizure pattern with very variable etiologies
and generally poor outcome.
Seizure type: infantile spasms (usually at least one cluster per day or more). usually
associated with decline in behavioral function.
Etiology: variable: any bad brain condition in infancy can cause this: tuberous
sclerosis accounts for about 15% of cases; others, brain damage from perinatal
hypoxic-ischemic injury, infection, trauma, metabolic disorders, you name it!
Age: infancy: peak age 6 months.
EEG: hypsarrhythmia: see above.
Treatment: ACTH; vigabatrin (only available in civilized countries, not the US)
Prognosis: very poor; although some, if treated early and no cause evident, can do
well.
F. Lennox-Gastaut syndrome. The most characteristic malignant seizure disorder of
childhood. Involves frequent, mixed seizures that are hard to control usually
associated with severe developmental decline.
Seizure types: mixed seizures with absence, atypical absence, myoclonic, astatic and
generalized tonic-clonic. Nocturnal generalized tonic seizures are common. Usually
associated with decline in behavioral and cognitive function, often leading to
intellectual impairment and/or autistic features.
Etiology: variable: sometimes due to the same conditions causing infantile spasms
at a younger age (e.g., tuberous sclerosis). Can evolve from infantile spasms.
However, often appears in otherwise completely normal children and no cause can be
discovered.
Age: 2-10 years (peak is 3-5).
EEG: slow generalized spike and wave discharges (2 to 2.5 cycles per second).
Treatment: often frustratingly unsuccessful: valproic acid, benzodiazepines,
felbamate.
Prognosis: very poor; although some can undergo unexpected remission or
improvement.
VII.
A. Evaluation:
1. Epilepsy is generally a clinical diagnosis arrived at by a careful history.
2. Since the patients consciousness is often impaired, the history must be
expanded by interviewing witnesses: family, friends, EMT personnel, police
officers, mistresses, fellow criminals, accomplices etc...
3. The details are important! Very carefully define the circumstances leading up
to the event (illness or not, lack of sleep, time of day, fever, drug use, alcohol
etc...). What is the individuals recollection of the event? Was there an aura?
What exactly happened during the event? Do not be satisfied by medical terms
used by non-medical or even other medical personnel. Clarify for yourself
exactly what happened. Was there a post-ictal phase etc...? For all this use the
mnemonic:
Hypoglycemia
Migraine
Drug reactions
Panic attack
Breatholding spells
Non-epileptic paroxysmal
event (pseudoseizure)
B. Treatment:
1. When to treat?
a. overall, the risk of recurrence after a single seizure is about 30%, but
many clinical factors affect this risk.
b. Treatment is indicated when 1) recurrence is likely, AND 2) the
individual seizures are either dangerous, occur during the day or are otherwise
disturbing, AND 3) they occur often enough.
(Example: children with benign rolandic epilepsy may have recurrence
weekly, but the seizures occur in bed during sleep, do not put the child at risk,
do not result in social stigmatization, and hence may not demand treatment.)
c. Treatment after a single seizure: usually, one does not treat with an
anticonvulsant (antiepileptic drug, AED) after a single seizure unless there is
an obvious risk of recurrence or the first seizure was prolonged (status
epilepticus). An obvious risk of recurrence typically exists if one of the
following is present: i) abnormal (epileptiform EEG), ii) structural lesion or
disease which is a focus for the seizure (tumor, stroke etc...), iii) close
relative with epilepsy of the same type who has required treatment.
d. Treatment after a recurrent seizure: usually, one does treat with an
anticonvulsant (antiepileptic drug, AED) after the second or subsequent
seizure unless there is a clear contraindication to treatment or treatment is
unnecessary (see reasons as above).
2. How to treat? Choice of anticonvulsant: (this is basically the subject of entire
courses. For this lecture you should remember the names of the five major drugs
and their clinical indications. Most importantly, remember which is the drug of
choice for what (underlined). The rest of the stuff is in there for your future use
or to ignore completely (had to satisfy my obsessive-compulsive tendencies).
a. The Meat of the Matter: The five BIG ones:
1. PHENOBARBITAL
indications: almost only for children under 2 years of age; Drug of choice
for neonates
dose: 5 mg/kg/day; adult: 90-180 mg/day
half-life: approx 24 hrs
dosing: daily or twice a day.
important side effects: cognitive blunting, behavioral, allergic skin reactions
serum monitoring: none
2. VALPROIC ACID (VPA; depakene, depakote)
indications: all idiopathic generalized seizures; also partial seizures. Drug
of choice for idiopathic generalized seizures of all types including absence
seizures.
dose: 20-60 mg/kg/day; adult: 750 -1500 mg/day
half-life: approx 8 hrs
dosing: twice or three times daily unless use sustained release preparation.
important side effects: hyperactivity, tremor, thrombocytopenia, hair loss,
liver damage can be fatal), pancreas damage (can be fatal).
serum monitoring: CBC, ALT.
3. PHENYTOIN (PHT; dilantin; fosphenytoin=cerebyx)
indications: generally not used in children except for status epilepticus;
commonly used in adults for partial seizures (all types) and some generalized
before next seizure begins, or more or less continuous seizure activity lasting greater
than 30 minutes. This is serious!
B. Types:
1. Generalized convulsive status epilepticus: The most common; just like it
sounds.
2. Non-convulsive status: the person is in fact conscious but in an altered
state (Encephalopathic or spacey). Usually response time is delayed, there is
often confusion and disorientation, and minor twitching or myoclonic
movements are often present. This can be either continuous absence seizures
(absence status) or continuous complex partial seizures (complex-partial status).
3. Epilepsia partialis continua: continuos focal seizures; consciousness usually
preserved.
C. Settings where status epilepticus occurs:
1. Severe metabolic disorders: hyponatremia, pyridoxine deficiency
2. Infection: herpes encephalitis, severe meningoencephalitis
3. Severe, diffuse head trauma.
4. subarachnoid hemorrhage; other acute hemorrhages.
5. abrupt withdrawal of anticonvulsants
6. treatment of absence epilepsy with carbamazepine: can precipitate absence
status.
7. sometimes first febrile seizure in a child consists of status epilepticus.
D. Mortality: 5 -15% or less; nevertheless, can have serious morbidity.
E. Convulsive status epilepticus:
1. Characteristics:
more or less generalized convulsions without cessation
imbalance between high energy demand in Brain and poor energy substrate delivery to
brain: the longer this lasts the worse the potential consequences.
as time progresses can result respiratory insufficiency, hypoxia, hypotension,
hyperthermia, eventual brain ischemia and rhabdomyolysis (muscle breakdown due to
excessive contraction)
represents a medical emergency
2. Management:
identify cause
stabilize patient (ABCs = Airway, Breathing, Circulation)
immediate labs: CBC, electrolytes, calcium, glucose, toxic screen imaging if needed)
treatment with anticonvulsants which have rapid onset of action and can be safely and
effectively delivered parenterally:
a) lorazepam (ativan) 0.05-0.1 mg/kg/dose IV or diazepam (valium) 0.2 to
0.3 mg/kg/dose IV
b) fosphenytoin 18-20 PEs /kg/dose IV; PE stands for phenytoin equivalents
which is how doses of this phenytoin prodrug are calculated.
c) phenobarbital 15-20 mg/kg/dose IV.
F. Absence status:
not as dire an emergency
treatment is with IV lorazepam or diazepam
discontinue offending agent (carbamazepine or phenytoin) if present
IV or enteral valproic acid
G. Complex partial status:
difficult to recognize
variable presentation
altered consciousness, spaciness, twilight state with ongoing
automatisms; can mimic some psychiatric diseases (catatonic states, etc...)
again, not as much of a dire emergency
treatment: recognition (often requires EEG monitoring) and medications
as in convulsive status epilepticus above.
F. Epilepsia partialis continua:
usually focal clonic movements of limited portion of the body (i.e., just
the hand, just the finger, corner of the mouth etc...)
often refractory to treatment
benzodiazepines (lorazepam and diazepam) effective at high dose but they
wear off quickly and have significant sedative side effects.
phenytoin, phenobarbital can be used.
often a focal lesion or a metabolic disease (mitochondrial encephalopathy)
is present.
a special case is Rasmussens Encephalitis (rare condition of children in
which there is progressive unilateral cortical atrophy and intractable focal
seizures of unknown cause-- possibly autoimmune antibody-mediated
reaction to glutamate receptors.
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epil00b.doc rev 8-21-02