NE URO LO GY

2 17 SEIZURES AND EPILEPSY

DR DAYRIT AND DRA DE GUZMAN

DEFINITION OF TERMS
SEIZURE
Transient & reversible alteration of behavior caused Most common etiology IDIOPATHIC
by a paroxysmal, abnormal & excessive neuronal
discharge 2/3 of all epileptic seizures begin in childhood
Symptom or sign 75% unclear etiology Idiopathic

Seizure Actual attack CLASSIFICATION OF SEIZURES
CEREBRAL PROBLEM Not spinal cord or muscle SEIZURES HAVE BEEN GROUPED IN SEVERAL WAYS:
problem
IF YOU HAVE RECURRENT SEIZURES YOU HAVE International League Against Epilepsy (ILAE)
EPILEPSY Philippine Version: Philippine League Against
SEIZURE DISORDERS SYNONYMOUS WITH Epilepsy (PLAE)
EPILEPSY [the term epilepsy is usually not used
because it brings stigma] ACCORDING TO
Presumed Etiology
Idiopathic (Primary)

EPILEPSY Usually childhood onset or with family history
2 or more seizures not directly provoked by
Symptomatic (Secondary)
intracranial infection, drug withdrawal, acute
metabolic changes or fever Secondary to a tumor, an old stroke, previous
OLD DEFINITION Due to an excessive and infection (meningitis)
disorderly discharge of cerebral nervous tissue on
muscles Site of Origin
Diagnosis Example: Coming from the Temporal Lobe
Temporal Lobe Epilepsy
Epilepsy Disorder/Disease
When you write the diagnosis, you put EPILEPSY Clinical Form
MANIFESTED BY SEIZURES Generalized
Focal
Frequency
Isolated
CONVULSION Cyclic
Intense paroxysm of involuntary repetitive muscular Repetitive
contractions Closely spaced sequence (Status Epilepticus)
Motor component of seizure Special Electrophysiologic Correlates
TAKE NOTE: Not all seizures are convulsions! Based on Electroencephalogram (EEG)

INCIDENCE OF EPILEPSY DISTINCTION IS MADE BETWEEN:
Prevalence: 5-10 per 1000 Classification of Seizures (clinical manifestations of
44 cases per 100,000 persons each year (US data) epilepsy; grand mal, petit mal, etc.) AND
10% will experience a seizure by age 80 Classification of Epilepsies or Epileptic Syndromes
Bimodal Distribution: which are disease constellations
1st year of life
Over 60 years old

Pediatric and geriatric population

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 - Myoclonic seen in patients in the ICU
CLASSIFICATION BASED ON THE INTERNATIONAL
Sleep jerks
CLASSIFICATION OF EPILEPTIC SEIZURES:
PARTIAL/FOCAL: occur within discrete regions of the
brain [one side of the brain] - Tonic
Simple Partial MOST COMMON - Clonic
- Atonic common in children
Intact level consciousness
Suddenly falls down due to loss of muscle tone
- Begin with MOTOR, SENSORY or AUTONOMIC
phenomena depending on the cortical region
- Tonic-Clonic
affected

o MOTOR MOST COMMON (Jacksnonian MOST COMMON: Generalized Tonic-Clonic

March) Seizures (GTC) Also called Grand Mal

Can occur when the patient is awake or asleep Seizures J
As compared to tremors Only seen when the
patient is awake
TONIC PHASE initial manifestations are
(+) Todds Paralysis transient hemiparesis
unconsiousness and tonic contractions of limb
after an attack
muscles (10-30 seconds)
o SOMATOSENSORY or Special Sensory o Expiration induces vocalizations (cry or
moan)
Patient sometimes feel numb or goosebumps o Cyanosis
o Contractions of masticatory muscles
o AUTONOMIC o Patient falls to the ground
o p CLONIC PHASE alternating muscle
Vomiting contraction and relaxation of symmetric limb
Diaphoretic jerking (30-60 secs or longer)
Cold clammy skin o Ventilatory efforts return immediately
after cessation of tonic phase and
o PSYCHIC COGNITIVE cyanosis clears
COMPLEX PARTIAL - with impaired consciousness o Mouth may froth with saliva
o AURA followed by impaired consciousness o Muscles may become flaccid
o Patient may appear awake but lost contact with o Sphincter relaxation may produce
the environemtn and do not respond to urinary incontinence
instructions or questions for few minutes o May remain unconscious for variable
o Usually stare or remain motionless or engage period of time
in repetitive semi-purposeful motor o If >2 mins STATUS EPILEPTICUS
behaviours called AUTOMATISMS chewing, RECOVERY PHASE regaining consciousness
grimacing, gesturing, lip smacking, snapping of maybe followed by post-ictal confusion and or
fingers headache
o May become hostile or aggressive if restrained o Full orienation in 10-30 minutes
o Seizure discharge arise form temporal lobe or (longer with status or pre-existing
medial frontal lobe structural or metabolic brain disorders)
o Symptoms take many forms but usually
sterotyped
o Epigastric symptoms are common MECHANISM OF SEIZURE INITIATION AND
o Affective (fear), Cognitive (dj vu), sensory PROPAGATION:
(olfactory hallucinations) 1. high frequency of action potentials
2. hypersynchronization
GENERALIZED EPILIPTOGENESIS transformation of a normal
Rise from both cerebral hemispheres simultaneously neuronal netweok that becomes chronically
Bilaterally symmetrical and without local onset hyperexcitable,
Types: KINDLING PHENOMENON a result of repeated
- Absence common in chilren stimulation of subconvulsive electrical pulses form
an established focus elsewhere; controversial in
Also called Petit Mal Seizure humans

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 o Epilepsy may evolve with increase in frequency,
NATURE OF THE DISCHARGING LESION IN duration or spread of the seizures
EPILEPSY: o Interictal EEG background is abnormally slow
- SEIZURES GENERATION REQUIRE THREE o Spontaneous resolution of epilepsy is unusual
CONDITION o Prognosis depends on the underlying neurologic
o Population of pathologically condition
excitable neurons II. Generalized Epilepsies and Syndromes
o An increase in excitatory Idiopathic, with age-related onset or Primary
glutaminergic activity through Generalized (BNFC, absence, JME, etc.)
recurrent connetions to spread the Symptomatic or Secondary Generalized (West
discharge - GLUTAMATE syndrome, Lennox-Gastaut syndrome)
o A reduction in the activity of the IDIOPATHIC EPILEPSY
normally inhibitory gabanergic
projections - GABA IDIOPATHIC EPILEPSY:
o as a rule, begin early in life
SPECIAL EPILEPTIC DISORDERS seen in o not associated with evidence of structural,
children nervous, or mental disorders
o Myoclonus and myoclonic seizures o normal interictal EEG background
o Reflex e pilepsy o favorable response to anti-epileptic
o Acquired aphasia with convulsive disorder therapy
o Febrile and other seizures of infancy and o benign prognosis with spontaneous
childhood resolution in time
o Hysterical seizures psychogenic

INTERNATIONAL CLASSIFICATION OF EPILEPSIES ABSENCE or PETIT MAL SEIZURES

AND EPILEPTIC SYNDROMES Pyknoepilepsy Pykno compact or dense
Features. brevity, frequency, paucity of motor activity
I. Localization-related "A moment of absentmindedness or day dreaming"
Idiopathic IDIOPATHIC EPILEPSY or PRIMAY o Without a warning.... sudden interruption of
EPILEPSY consciousness.... stares and briefly stops talking or
o There is no underlying cause indetifies other ceases to respond
than an heriditary predisposition
o 10 percent are completely motionless; the rest
o Presumed to be GENETIC of origin
have fine clonic (myoclonic) movements of eyelids,
o Ofthen with a (+) family history
facial muscles or fingers, at a rate of 3 per second
o As a rule, begins early in life 20 years old and
below EEG pattern of generalized 3-per-second spike-
o Not associated with evidence of structural or and-wave pattern
nervous or mental disorders After 2 to 10 seconds, or longer, patient reestablishes full
o Normal interictal EEG background and MRI contact with the environment and resumes pre-seizure
activity.
Inter-ictal Period in between episodes of
seizures (Time wherein the patient is not Hyperventilation may induce an attack
undergoing seizure) As many as several hundred may occure in a day
Rarely begins before 4 years or after puberty
o Favorable response to antiepileptic therapy Attacks tend to diminish during adolescence and
o Benign prognosis with spontaneous resolution in then disappear, to be raplaced by other forms of
time generalized seizure
Symptomatic Secondary Epilepsy "SECONDARY" epilepsy
o Seizures have an identifiable and acquired o Seizures have an identifiable and acquired
structural cause
structural cause
Difficult to control, treat, and manage o There is evidence for focal or generalized
neurological disease
o There is evidence for focal or generalized o mental retardation or deterioration may occur
neurological disease o Rarely begins before 4 years, or after puberty
o Mental retardation or deterioration may occur o As many as several hundreds may occur in a day

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 o Attacks tend to diminish during adolescence and then changes at the molecular level - the most
disappear, to be replaced by other forms of prominent of these are alterations in the
generalized seizures composition and expression of GABAA receptors on
the surface of hippocampal dentate granule cells
MESIAL TEMPORAL LOBE EPILEPSY normally, GABAA receptors in adults, which consist
Hippocampal sclerosis: of five subunits, serve as inhibitors, hyperpolarizing
o there is selective loss of neurons in the dentate hilus the neuron by allowing passage of chloride
and the hippocampal pyramidal-cell layer ions when activated
o relative preservation of dentate granule cells and a
small zone of pyramidal cells (in the cornu ammonis, PATHOLOGY OF EPILEPSY
field 2, of the hippocampus) Primary generalized epilepsies: majority are grossly
o the dense gliosis that accompanies the loss of neurons and microscopically normal
causes shrinkage and hardening of tissue Symptomatic epilepsies: neuronal loss and gliosis,
o the term "mesial temporal sclerosis" has also been used for porencephaly, hamartoma, heterotopia, dysgenetic cortex,
this lesion, because often there is neuronal loss in the vascular malformations, and tumor
neighboring entorhinal cortex and amygdaladebate Focal epilepsies: gliosis, fibrosis, vascularization,
about whether hippocampal sclerosis is a cause or an meningocerebral cicatrix, hippocampal sclerosis
effect of seizures SEIZURE IN ADULTS
o it has been seen in a wide variety of epileptic conditions,
including cryptogenic temporal-lobe epilepsy and Secondary to medical diseases
epilepsy that follows febrile seizures or other brain o Withdrawal seizures AED withdrawal
insults early in life, as well as in animal models of head o Infections CNS, or systemic infections
injury and seizures induced by chemicals o Metabolic encephalopathies hypoglycemia,
o Hypotheses about the mechanism of epileptogenesis hyponatremia, uremia, hepatic encephalopathy
structural r eorganization o Medications as a cause of seizures antibiotics
selective n euronal l oss (carbapenem), tricyclic antidepressants
neurogenesis o Global arrest of circulation and cerebrovascular
molecular alterations, such as changes in diseases hypoxic encephalopathy
neurotransmitter receptors o Acute head injury
o Some investigators have suggested that the selective
vulnerability of certain neurons may be a mechanism of SEIZURE IN ADULTS
epileptogenesis in hippocampal sclerosis
o In animal models, excitatory interneurons located within Sodium Channels
the dentate gyrus, which normally activate inhibitory o Familial generalized seizures
interneurons, appear to be selectively lost o Benign Familial neonatal convulsions
o Loss of these excitatory cells would be expected to Potassium Channels
impair the inhibitory feedback and feed-forward o Benign i nfantile e pilepsy
mechanisms that act on dentate granule cells, resulting o Episodic ataxia type 1
in hyperexcitability Ligand-gated Channels
o An intriguing hypothesis lies in the phenomenon of o Autosomal dominant nocturnal frontal seizures
neurogenesis o Familial generalized and febrile seizures
Almost all neurons in the brain are postmitotic o Juvenile myoclonic epilepsy
and do not divide in adults, but progenitor cells in Calcium C hannel
the dentate gyrus of the hippocampus are known o Episodic ataxia type 2
to divide
Postnatal neurogenesis in the hippocampus DIAGNOSTICS
can occur throughout life EEG
The potential clearly exists for an imbalance o Indications:
between excitation and inhibition as new neurons To confirm the diagnosis of epilepsy
differentiate and form synaptic connections An adequate EEG should include a sleep and
awake recording

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 To classify the seizure type o Need t o c onfirm d iagnosis
To make a diagnosis of non-convulsive status o Poor seizure control
epilepticus o Severe/toxic s ide e ffects
o Role of Interictal EEG in Epilepsy o Patients planning a pregnancy
Confirms clinical diagnosis of epilepsy o Seizure free patient considering drug withdrawal
Classification of seizure types
CAUSES OF RECURRENT SEIZURES IN DIFFERENT AGE
Definition of Epileptic syndromes
GROUPS (Adams, 19th Edition)
Monitoring of response to AED treatment
Neonates
Evaluation of patients with single
Congenital Maldevelopment
seizures
Birth Injury
Guide in the decision to discontinue AED
Anoxia
treatment
Metabolic Disorder
BRAIN IMAGING (MRI or CT)
- Hypocalcemia
o Indications:
- Hypoglycemia
Partial onset seizures at any age
- Vitamin B6 Deficiency
Adult onset seizure of any type
- Biotinidase Deficiency
Presence of focal neurologic deficit CT and
- Phenylketonuria
MRI allow identification of structural lesions
- Others
MRI higher specificity and sensitivity in

diagnosing congenital brain anomalies,
Infancy (1-6 months)
hippocampal sclerosis, AV malformations,
As above
tumors
Infantile Spasms (West Syndrome)
CT scan : if MRI is not available or in those with

pacemakers. aneurysm clips, severe
Early Childhood (6 months 3 years)
claustrophobia
Infantile Spasms
DIFFERENTIAL DIAGNOSES
Febrile Convulsions
o Syncope/Faints
Birth Injury and Anoxia
o TIA
Infections
o Drop attacks
Trauma
o Complicated migraine
Metabolic Disorders
o Hypertensive emergency
Cortical Dysgenesis
o Psychiatric disorders
Accidental Drug Poisoning

Childhood (310 years)

Perinatal Anoxia
TREATMENT Injury at birth or later
Infections
CRITERIA FOR STARTING ANTIEPILEPTIC DRUG Thrombosis of Cerebral Arteries or Veins
(AED) Metabolic Disorders
o The diagnosis of epilepsy must be firm and definite Cortical Malformations
o Risk of seizure recurrence must be sufficient Lennox-Gastaut Syndrome
o Seizure type or epilepsy syndrome The AIM of Idiopathic (Probably Inherited)
Treatment with AEDs is to prevent seizures for the Rolandic Epilepsy
following reasons:
Prevent injury Adolescence (10-18 years)
Avoid disruption to employment or education Idiopathic Epilepsy (Including genetically transmitted
Minimize the social consequences of the types)
condition Juvenile Myoclonic Epilepsy
Try to prevent status epilepticus Trauma
WHEN T O R EFER T O A SPECIALIST Drugs

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 Lamotrigine
Early Adulthood (18-25 years)
MYOCLONIC Valproate Topiramate
Idiopathic Epilepsy
Trauma Levetiracetam
Neoplasm
Zonisamide
Withdrawal from alcohol or other sedative drugs
Partial Carbamazepine Valproate
Middle Age (35-60 years)
Trauma Phenytoin Lamotriging
Neoplasm Oxcarbazepine
Vascular Disease
Alcohol or other drug withdrawal Levetiracetam
Drug Partia Generaliz Toni Absenc Myoclon Mixe
l ed c e us d
Late Life (Older than 60) secondary Clon
Vascular Disease (usually postinfarction) ic

Tumor
Carbamazep + + + x x o
Abscess ine
Degenerative Disease
Trauma Clonazepam + + + ? ? +

Phenobarbit + + + o ? + ?

al

Phenytoin + + + x x o

Valproate + + + + + +

MEDICATION SIDE EFFECTS

Phenobarbital Sedation, sleepiness,

hyperactivity, weakness

Dilantin Dizziness, poor balance,

Phenyhydantoin, weakness, thick gums,
Phenytoin excessive hair growth,
allergic rash, SJS

Tegretol Allergic rash, dizziness,

Carbamazepine sleepiness, weakness,
headache, gastric
discomfort, SJS, leukopenia,
hyponatremia

WHAT DRUG TO CHOOSE: Epival/Depakene Transient loss of appetite,
alopecia, nausea, vomiting,
EFFICACY ESTABLISHED AED AGAINST COMMON weight gain
SEIZURE D RUGS:
Rivotril Clonazepam Sleepiness, weakness, in
SEIZURE TYPE FIRST LINE SECOND LINE chidren increase bronchial
TONIC CLONIC Valproate Lamotrigine secretions

Trileptal Headache, dizziness,

Carbamazepine
Oxcarbazepine sleepiness, nausea and
Phenytoin hyponatremia

ABSENCE Valproate Ethosuximide

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 Neurontin Gabapentin Sleepiness, fatigue,
dizziness, weakness and 6-9 ABCs, Establish Fosphenytoin
IV, Blood work, (20 m g/kg PE)
rashes Give Thiamine
and glucose
Lamictal Lamotrigine Allergic rash, drowsiness

Topamax Weight loss, mood changes, 10-20 Lorazepam (0.1

sleepiness, dizziness and mg/kg) or
kidney stones Diazepam (0.2
mg/kg)

21-40 Phenytoin (15- Add phenytoind
- start at the lowest computed appropriate dose and 20 m g/kg) (5 gm/kg) /
increase slowly until seizure control is achieved or fosphenytoin (5
side effects develop mg/kg) followed
- Titrate slowly to allow tolerance to CNS side effects by Phenobarbital
- Keep the regimen simple wth OD- BID dosing, if (20 m g/kg) or go
possible to anesthesia

SURGICAL TREATMENT 41-60 Add

phenobarbital
- temporal lobectomy- 50% improvement in 5 years (5-10 m g/kg)
in complex partial seizures
- Corpus callostomy recommended for cotnrol of
Greater than 60 Add phenytoin Anesthesia with
intractable partial and secondary generalized
(5 mg.kg) x 2 Midazolam or
seizures especially atonic drop attacks
followed by Propofol
- Hemispherectomy recommended for severe and
phenobarbital
extensive unilateral cerebral disease with
(20 mg/kg)
intractable m otor seizures and hemiplegia
followed by
o Rasmussens encephalitis, Sturge-Weber
pentobarbital
syndrome and Large porencephalic Cysts
ROLE OF KETOGENIC AND MEDIUM CHAIN
FACTORS RELATED TO SUCCESSFUL WIDTHRAWAL OF
TRIGLYCERIDE DIET:
AEDs
- exact m echanism U NKNOWN
- Single type of lesion
- chronic ketosis induced by a diet high in fat results
- Normal neurologic examination
in improvement of cerebral energetics and
- Normal IQ
augmentation of G ABA effects (?)
- Normal E EG following treatment
- used m ainly in children (1-10 years old)
COMPLICATIONS OF THE DISEASE: - 2/3 reduction in seizure frequency and reduction
of A ED usage
- STATUS EPILEPTICUS - Effective in refractory epilepsy
o Recurrent generalized convulsions at a - CHARACTERISTICS:
frequency that prevents regaining of o Consists of daily regimen of 1g.kg p rotein
conciousness in the interval between seizures o Enough fat to make up desired caloric
o Prolonged convulsive status (longer than 30 requirements
mins.) carries high risk for serious neurologic o Very small amount of carbs
sequelae (epileptic encephalopathy o Ketogenic : antiketogenic potential ratio 3:1
o MANAGEMENT - Caloric D istribution:
o Ketogenic 87% fat, 6 % CHO and 7% CHON
o MCT 60% MCT, 11% fat, 19% CHO and 10%
Time in M inutes Standard Proposed CHON
Treatment Treatment o Thus m ore palatable and no increase in plasma
cholesterol
0-5 Diagnosis and Lorazepam (1.0
assessment mg/kg)

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