Seizures and epilepsy

Epilepsy is a chronic cerebral disorder characterized by

recurrent seizures.

Seizures are paroxistic clinical manifestations taking usually

seconds to minutes and having a variable content: motor, somatosensory, psychiatric, cognitive, or autonomic. Usually we have to
deal with positive phenomena (clonias, visual hallucinations, ictal
speech etc.) but some negative symptoms might occur as well
(aphasia, hemianopia, ictal motor deficit).
Seizures occuring during an acut neurological disorder are strictly
related to the acute damage of cortical neurons as a consequence
of pathological process. Seizures are nothing more than a clinical
sign (as Babinski sign is). This is not epilepsy!!!!!
For instance acute encephalitis could be manifested by fever, altered mental
status and seizures.
Seizures in this case are a clinical hallmark of the inflammatory process.
If seizures restart at distance from acute episode, after healing of
inflammatory lesions we have to deal this time with postinfectious epilepsy a
chronic disorder.

Physiopathological base for seizures is a process of hyperexcitability in a

group of cortical neurons that we call seizure focus.
As a consequence, seizures are the clinical expression of a lesion that
affects cortical neurons.
Seizure semiology is highly dependant on the location of the seizure focus .
We call seizures originating in restricted parts of the cerebral cortex - focal
(partial) seizures. Focal seizures are encountered in localization related
epilepsies.
On the contrary when seizures appear to begin bilaterally, neuronal
hyperexcitability or loss of inhibitory mechanisms affects more widespread
the cortex of cerebral hemispheres and clinical expression is a generalized
seizure (with loss of counsciousness from the very first moment). Primary
generalized seizures occurs in idiopathic epilepsy and have a genetic basis
or could be provoked by toxic or metabolic conditions
Paraclinical diagnosis of epilepsy is based on two critical aspects:
Prove the epileptogenic process electroencephalography
Search of a structural lesion that could be the cause MRI and
functional imagistic studies

Seizures classification

Generalized seizures abrupt initial loss of consciousness

Generalized tonic clonic seizures
Absence seizures
Myoclonic seizures
Atonic seizures (one of the most severe type, onset only
during childhood, hallmark of intractable, deteriorating
epilepsies like Lennox Gastaut syndrome)
Focal (partial) seizures consciousness retained, patient
able to describe the clinical content of his seizures
Simple focal seizures consciouness retained during the whole episode
Complex focal seizure complex semiology, impairment of
consciousness at some point during the episode. Seizure focus located
in a cortical zone responsible for highly complex, integrative functions
usually temporal or frontal lobes or propagation of seizures into such
complex cortical territories (hippocampal structures, orbitofrontal
cortex etc.)
Simple or complex focal seizures wirh secondary tonic-clonic
generalization.

Trained doctors or nurses are generally able to adequately interact with a

patient during a seizure and interrogate after, to reveal all the reliable
clinical aspects of a seizure.

Impairment of consciousness is
considered in a nonresponsive
patient and unable to perform tasks
during seizures also amnestic for the
episode (total or partial) when
patient is questioned afterward.

Generalized tonic-clonic seizure (epileptic grandmal)

Sudden loss of consciousness

Patient is falling and usually is screaming (laringian muscles
contraction)
Apnea and cyanosis occur as consequence
Tonic phase (~ 40 sec) generalized tonic contraction initially in
flexion, then extension,
Eyes wide open,
Autonomic signs: hypersalivation and drooling, sweating, tachycardia,
rising blood pressure
Clonic phase (~20 sec) intermittent relaxation from the tonic
contraction status
Urinary incontinence occurs and tongue is bitten on its lateral aspect
postictal coma nonlateralized coma status with generalized loss of
muscles tone, midriasis and bilateral Babinski sign
Progressively patient becames reoriented but has no recollection of
the ictal episode

Absence seizure (petit mal)

Abrupt loss of contact
Motor arrest but patient does not fall
Some activities might continue (like
driving a car or manipulating an object
etc..)
Fine myoclonic movements occur
rhythmical (3Hz) on the eyelids or
involves other muscles as well
Might be very frequent pyknolepsia
Rarely have their onset under 4 years
of age or after puberty

Simple partial seizures

Consciousness retained
Motor, sensory paresthetic, visual,
vertiginous, olfactory, aphasic
Patient able to describe in detail
what happens during the episode

Complex partial seizures

Aura initial event in the seizure frequently
temporal epilepsy consist in rising epigastric
sensation or fear or experiential sensations (dj
vu, deja vecu)
Period of altered behavior and responsiveness for
which the patient is found later to be amnesic
(impairment of consciousness)
The motor component of a seizure occurs later
during the seizure and takes form of so called
automatisms oroalimentary (chewing,
swallowing), gestual, verbal.

 Each type of epilepsy presents with its own

unique combination of seizure type, typical
age of onset, EEG findings, treatment, and
prognosis.
The most widespread classification of the
epilepsies devides epilepsy syndromes by
location or distribution of seizures (as reve
aled by the appearance of the seizures and by
EEG) and by cause.
Syndromes are divided into
localization-related epilepsies
generalized epilepsies
epilepsies of unknown localization.

Localization related
epilepsies
Presence of lesional zone in the brain (frontal,

temporal, parietal , occipital) that has been

acquired at some point in life
from the first weeks of gestation (intrauterine
developmental lesions like focal cortical
dysplasia, disembrioplastic tumors etc)
to older ages: vascular, traumatic,
inflammatory
Early lesions have a great impact on cerebral
development and could be associated with
cognitive delay

Generalized epilepsies
Idiopathic - Genetic disorders, age dependant
penetrance
Onset typically before 18 y of age
Non - lesional MRI
Generalized discharges on EEG - very typical EEG
patterns that confirms the diagnosis
Very sensitive to sleep deprivation
Most representative:
Childhood absence epilepsy onset around 6-8y of
age, good prognosis,
Juvenile myoclonic epilepsy onset in adolescence,
life long condition, myoclonic seizures, generalized
tonic clonic seizures, absence seizures

Diagnosis
Anamnesis precise interrogation about
the seizure semiology asking the patient,
relatives, witnesses
Standard EEG recording scalp electrodes,
30 min recording, patient awaken, relaxed,
3 hiperventilation, eyes open, eyes shut.
If no abnormalities activation procedures
like sleep deprivation, sleep recordings
(especially in children)

Electroencephalography
Normal background patient awake,
eyes shut posterior alpha rhythm,
well modulated

interictal epileptiform abnormalities

Interictal sharp waves

 Right anterior temporal spikes

common abnormality in temporal
epilepsy

Generalized polispike and waves

discharges encountered in juvenile
myoclonic epilepsy

Imaging studies
Emergency condition first seizure or
cluster of seizures - CT scan is likely
to reveal the most striking lesions
responsible for seizures:
Tumors
Stroke
Subdural hematoma
Traumatic scars
Cerebral venous thrombosis etc..

Imaging studies
Most of the lesions responsible for focal
epilepsies are very well depicted by MRI
1,5 T in T1 weighted images, T2 and FLAIR
Metabolic studies are used in MRI negative
cases:
PET using fluorodeoxiglucose (FDG) is used
interictal (interval between seizures) to reveal
the hypometabolic area associated to the
seizure focus
SPECT is used to reveal ictal (during seizure)
hyperperfusion associated to the seizure focus

Imaging studies

Right hippocampal sclerosis hypersigna

right hippocampal structures
in a patient with
mesiotemporal epilepsy

 Right temporoparietal
Polymicrogiria malformation
of cortical development

Acute seizures
Treatment to stop seizing and finding
cause is an emergency
Depending of the clinical pattern:
Generalized: toxic, metabolic screening,
CSF analysis (LP)
Focal: valuable clinical sign for a focal
cortical lesion generally contralateral
to the limbs with motor symptoms
Imiging studies are prevalent to
electroencephalography!!!

Etiology of seizures and

epilepsy

Onset 0-3 y of age

Injury at birth: anoxia, vascular
Traumatic
Postinfectious
Vascular
Metabolic
Toxic
Idiopathic

 Onset 3-18 y of age

Idiopathic genetic
Traumatic
Infectious
Vascular
Tumors
Metabolic

 Onset 18-40 y of age

Traumatic
Primary cerebral tumors
Infectious
Metabolic
Toxic
Vascular
Rarely idiopathic

 Onset over 40y

Vascular
Metastatic tumors
Degenerative
Infectious
Traumatic
Metabolic
Toxic

Treatment
Acute treatment of a seizure:
Check vital functions and start support if
needed
Iv. Benzodiazepine with short T1/2
(diazepam, lorazepam)

 Status epilepticus: seizing for more

then 30 min.
Generalized tonic-clonic status
medical emergency life threatening
condition
Support vitals
O2, iv line
Short half life Benzodiazepine
Iv phenitoin 20mg/kc (caution with
cardiac block)
Iv phenobarbital 20mg/kc
Intubated patient - pentobarbital

Chronic treatment
Principles:
Seizure freedom
No side effects
Start an AED in monotherapy
If failure switch to an other AED monotherapy
Make the switch slowly, progressive
If failure try a reasonable combination
If failure after 1 year of combination treatment
declare pharmacoresistance and refer to
presurgical evaluation if is a focal epilepsy

Chronic treatment
Focal epilepsies
First line: carbamazepine
Second line: lamotrigine, levetiracetam,
oxcarbazepine, topiramate

Idiopathic Generalized epilepsies

First line: valproat
Second line: etosuximid (only for absence
seizures), lamotrigine (may aggravate
myoclonic seizures), levetiracetam (may not
be very effective)

Side effects of AED

CBZ: vetigo, ataxia, sedation, double vision,
hematologic, cardiac, hyponatremia, rash
LTG: rash, allergic - inflammatory reaction,
insomnia
LEV: sedation, agressivity, irritability, affective
reactions
VPA: sedation, hepatic toxicity, ponderal gain,
hair fall, ovarian policystosis???, parkinsonism
OXC: vertigo, ataxia, double vision,
hyponatremia

Epilepsy surgery
Candidates: patients with focal
pharmacoresistant epilepsy
Target: remove the epileptogenic zone
preserving the eloquent, functional
corte and rend the patient seizure free
The most common intervention with
70-90% chance of healing is for
mesiotemporal epilepsy due to
unilateral hippocampal sclerosis

Presurgical protocol
Surface video-EEG long term monitoring
with the aim to record habitual seizures
and interpret data anatomo-electroclinical to establish a hypothesis
If data obtained are concordant with the
lesion present on MRI and functional
cortex (language areas, motor, visual
cortex) could be safely spared planning
surgery with high chance of seizure
freedom

 Discordant data or MRI negative cases

impose implantation of intracerebral
electrodes and further verification of
initial hypothesis.
If safe and beneficial tailored cortical
resection
After surgery, if successful therapy
might be tapered down only after 2
years of good outcome.