• Example: Coming from the Temporal Lobe à Temporal Lobe Epilepsy
DEFINITION OF TERMS • SEIZURE
ü Transient & reversible alteration of behavior caused by a paroxysmal, abnormal & excessive neuronal discharge
ü Symptom or sign
• EPILEPSY
ü 2 or more seizures not directly provoked by intracranial infection, drug withdrawal, acute metabolic changes or fever
ü OLD DEFINITION – “Due to an excessive and disorderly discharge of cerebral nervous tissue on muscles”
ü Diagnosis
• CONVULSION
ü Intense paroxysm of involuntary repetitive muscular contractions
ü Motor component of seizure
INCIDENCE OF EPILEPSY • Prevalence: 5-‐10 per 1000
• 44 cases per 100,000 persons each year (US data) • 10% will experience a seizure by age 80
• Bimodal Distribution: ü 1st year of life
ü Over 60 years old
• 2/3 of all epileptic seizures begin in childhood • 75% unclear etiology à Idiopathic
CLASSIFICATION OF SEIZURES
SEIZURES HAVE BEEN GROUPED IN SEVERAL WAYS:
ACCORDING TO… • Presumed Etiology
ü Idiopathic (Primary)
ü Symptomatic (Secondary)
• Site of Origin
• Clinical Form ü Generalized ü Focal • Frequency ü Isolated ü Cyclic ü Repetitive
ü Closely spaced sequence (Status Epilepticus) • Special Electrophysiologic Correlates
DISTINCTION IS MADE BETWEEN:
• Classification of Seizures (clinical manifestations of epilepsy; grand mal, petit mal, etc.) AND
• Classification of Epilepsies or Epileptic Syndromes which are disease constellations
NEUROLOGY
SEIZURES AND EPILEPSY DR DAYRIT AND DRA DE GUZMAN2 1 7
• Seizure à Actual attack• CEREBRAL PROBLEM à Not spinal cord or muscle problem
• IF YOU HAVE RECURRENT SEIZURES – YOU HAVE EPILEPSY
• SEIZURE DISORDERS – SYNONYMOUS WITH EPILEPSY [the term epilepsy is usually not used because it brings stigma]
• Epilepsy à Disorder/Disease
• When you write the diagnosis, you put EPILEPSY • MANIFESTED BY SEIZURES
• TAKE NOTE: Not all seizures are convulsions!
• Pediatric and geriatric population
• Most common etiology à IDIOPATHIC
• International League Against Epilepsy (ILAE) • Philippine Version: Philippine League Against
Epilepsy (PLAE)
• Usually childhood onset or with family history
• Secondary to a tumor, an old stroke, previous infection (meningitis)
CLASSIFICATION BASED ON THE INTERNATIONAL CLASSIFICATION OF EPILEPTIC SEIZURES:
• PARTIAL/FOCAL: occur within discrete regions of the brain [one side of the brain]
ü Simple Partial – MOST COMMON
- Begin with MOTOR, SENSORY or AUTONOMIC phenomena depending on the cortical region affected
o MOTOR – MOST COMMON (Jacksnonian March)
o SOMATOSENSORY or Special Sensory
o AUTONOMIC o p
o PSYCHIC – COGNITIVE
ü COMPLEX PARTIAL -‐ with impaired consciousness o AURA followed by impaired consciousness o Patient may appear awake but lost contact with
the environemtn and do not respond to instructions or questions for few minutes o Usually stare or remain motionless or engage
in repetitive semi-‐purposeful motor behaviours called AUTOMATISMS – chewing, grimacing, gesturing, lip smacking, snapping of fingers
o May become hostile or aggressive if restrained o Seizure discharge arise form temporal lobe or
medial frontal lobe
o Symptoms take many forms but usually sterotyped
o Epigastric symptoms are common
o Affective (fear), Cognitive (déjà vu), sensory (olfactory hallucinations)
• GENERALIZED
ü Rise from both cerebral hemispheres simultaneously ü Bilaterally symmetrical and without local onset ü Types:
- Absence – common in chilren
- Myoclonic – seen in patients in the ICU
- Tonic - Clonic
- Atonic – common in children
- Tonic-‐Clonic
• Intact level consciousness
• Can occur when the patient is awake or asleep • As compared to tremors à Only seen when the
patient is awake
• (+) Todd’s Paralysis – transient hemiparesis after an attack
• Patient sometimes feel numb or “goosebumps”
• Vomiting • Diaphoretic • Cold clammy skin
• MOST COMMON: Generalized Tonic-‐Clonic Seizures (GTC) à Also called Grand Mal Seizures J
• Also called Petit Mal Seizure
• Suddenly falls down due to loss of muscle tone • “Sleep jerks”
MECHANISM OF SEIZURE INITIATION AND PROPAGATION:
1. high frequency of action potentials 2. hypersynchronization
EPILIPTOGENESIS – transformation of a normal neuronal netweok that becomes chronically hyperexcitable,
“KINDLING PHENOMENON” – a result of repeated stimulation of subconvulsive electrical pulses form an established focus elsewhere; controversial in humans
• TONIC PHASE – initial manifestations are unconsiousness and tonic contractions of limb muscles (10-‐30 seconds)
o Expiration induces vocalizations (cry or moan)
o Cyanosis
o Contractions of masticatory muscles o Patient falls to the ground
• CLONIC PHASE – alternating muscle contraction and relaxation of symmetric limb jerking (30-‐60 secs or longer)
o Ventilatory efforts return immediately after cessation of tonic phase and cyanosis clears
o Mouth may froth with saliva o Muscles may become flaccid
o Sphincter relaxation may produce urinary incontinence
o May remain unconscious for variable period of time
o If >2 mins – STATUS EPILEPTICUS • RECOVERY PHASE – regaining consciousness
maybe followed by post-‐ictal confusion and or headache
o Full orienation in 10-‐30 minutes (longer with status or pre-‐existing structural or metabolic brain disorders)
• SPECIAL EPILEPTIC DISORDERS – seen in children
o Myoclonus and myoclonic seizures o Reflex epilepsy
o Acquired aphasia with convulsive disorder o Febrile and other seizures of infancy and
childhood
o Hysterical seizures – “psychogenic”
INTERNATIONAL CLASSIFICATION OF EPILEPSIES AND EPILEPTIC SYNDROMES
I. Localization-‐related
ü Idiopathicà IDIOPATHIC EPILEPSY or “PRIMAY EPILEPSY”
o There is no underlying cause indetifies other than an heriditary predisposition
o Presumed to be GENETIC of origin o Ofthen with a (+) family history
o As a rule, begins early in life – 20 years old and below
o Not associated with evidence of structural or nervous or mental disorders
o Normal interictal EEG background and MRI
o Favorable response to antiepileptic therapy o Benign prognosis with spontaneous resolution in
time
ü Symptomatic à Secondary Epilepsy
o Seizures have an identifiable and acquired structural cause
o There is evidence for focal or generalized neurological disease
o Mental retardation or deterioration may occur
o Epilepsy may evolve with increase in frequency, duration or spread of the seizures
o Interictal EEG background is abnormally slow o Spontaneous resolution of epilepsy is unusual o Prognosis depends on the underlying neurologic
condition
II. Generalized Epilepsies and Syndromes
ü Idiopathic, with age-‐related onset or Primary Generalized (BNFC, absence, JME, etc.)
ü Symptomatic or Secondary Generalized (West syndrome, Lennox-‐Gastaut syndrome)
ü IDIOPATHIC EPILEPSY
ABSENCE or PETIT MAL SEIZURES ü Pyknoepilepsy – “Pykno” – compact or dense” ü Features. brevity, frequency, paucity of motor activity ü "A moment of absentmindedness or day dreaming"
o Without a warning.... sudden interruption of consciousness.... stares and briefly stops talking or ceases to respond
o 10 percent are completely motionless; the rest have fine clonic (myoclonic) movements of eyelids, facial muscles or fingers, at a rate of 3 per second EEG pattern of generalized 3-‐per-‐second spike-‐ and-‐wave pattern
ü After 2 to 10 seconds, or longer, patient reestablishes full contact with the environment and resumes pre-‐seizure activity.
ü Hyperventilation may induce an attack
ü As many as several hundred may occure in a day ü Rarely begins before 4 years or after puberty ü Attacks tend to diminish during adolescence and
then disappear, to be raplaced by other forms of generalized seizure
ü "SECONDARY" epilepsy
o Seizures have an identifiable and acquired structural cause
o There is evidence for focal or generalized neurological disease
o mental retardation or deterioration may occur o Rarely begins before 4 years, or after puberty • NATURE OF THE DISCHARGING LESION IN
EPILEPSY:
-‐ SEIZURES GENERATION REQUIRE THREE CONDITION
o Population of pathologically excitable neurons
o An increase in excitatory glutaminergic activity through recurrent connetions to spread the discharge -‐
↑
GLUTAMATEo A reduction in the activity of the normally inhibitory gabanergic
projections -‐
↓ GABA
• IDIOPATHIC EPILEPSY:o as a rule, begin early in life
o not associated with evidence of structural, nervous, or mental disorders
o normal interictal EEG background o favorable response to anti-‐epileptic
therapy
o benign prognosis with spontaneous resolution in time
• Difficult to control, treat, and manage • Inter-‐ictal à Period in between episodes of
seizures (Time wherein the patient is not undergoing seizure)
o Attacks tend to diminish during adolescence and then disappear, to be replaced by other forms of generalized seizures
MESIAL TEMPORAL LOBE EPILEPSY ü Hippocampal sclerosis:
o there is selective loss of neurons in the dentate hilus and the hippocampal pyramidal-‐cell layer
o relative preservation of dentate granule cells and a small zone of pyramidal cells (in the cornu ammonis, field 2, of the hippocampus)
o the dense gliosis that accompanies the loss of neurons causes shrinkage and hardening of tissue
o the term "mesial temporal sclerosis" has also been used for this lesion, because often there is neuronal loss in the neighboring entorhinal cortex and amygdaladebate about whether hippocampal sclerosis is a cause or an effect of seizures
o it has been seen in a wide variety of epileptic conditions, including cryptogenic temporal-‐lobe epilepsy and epilepsy that follows febrile seizures or other brain insults early in life, as well as in animal models of head injury and seizures induced by chemicals
o Hypotheses about the mechanism of epileptogenesis § structural reorganization
§ selective neuronal loss § neurogenesis
§ molecular alterations, such as changes in neurotransmitter receptors
o Some investigators have suggested that the selective vulnerability of certain neurons may be a mechanism of epileptogenesis in hippocampal sclerosis
o In animal models, excitatory interneurons located within the dentate gyrus, which normally activate inhibitory interneurons, appear to be selectively lost
o Loss of these excitatory cells would be expected to impair the inhibitory feedback and feed-‐forward mechanisms that act on dentate granule cells, resulting in hyperexcitability
o An intriguing hypothesis lies in the phenomenon of neurogenesis
§ Almost all neurons in the brain are postmitotic and do not divide in adults, but progenitor cells in the dentate gyrus of the hippocampus are known to divide
§ Postnatal neurogenesis in the hippocampus can occur throughout life
§ The potential clearly exists for an imbalance between excitation and inhibition as new neurons differentiate and form synaptic connections
§ changes at the molecular level -‐ the most prominent of these are alterations in the composition and expression of GABAA receptors on the surface of hippocampal dentate granule cells § normally, GABAA receptors in adults, which consist
of five subunits, serve as inhibitors, hyperpolarizing the neuron by allowing passage of chloride ions when activated
PATHOLOGY OF EPILEPSY
ü Primary generalized epilepsies: majority are grossly and microscopically normal
ü Symptomatic epilepsies: neuronal loss and gliosis,
porencephaly, hamartoma, heterotopia, dysgenetic cortex, vascular malformations, and tumor
ü Focal epilepsies: gliosis, fibrosis, vascularization, meningocerebral cicatrix, hippocampal sclerosis
SEIZURE IN ADULTS
ü Secondary to medical diseases
o Withdrawal seizures — AED withdrawal o Infections — CNS, or systemic infections o Metabolic encephalopathies — hypoglycemia,
hyponatremia, uremia, hepatic encephalopathy o Medications as a cause of seizures — antibiotics
(carbapenem), tricyclic antidepressants o Global arrest of circulation and cerebrovascular
diseases — hypoxic encephalopathy o Acute head injury
SEIZURE IN ADULTS ü Sodium Channels
o Familial generalized seizures
o Benign Familial neonatal convulsions ü Potassium Channels
o Benign infantile epilepsy o Episodic ataxia type 1 ü Ligand-‐gated Channels
o Autosomal dominant nocturnal frontal seizures o Familial generalized and febrile seizures o Juvenile myoclonic epilepsy
ü Calcium Channel o Episodic ataxia type 2
DIAGNOSTICS ü EEG
o Indications:
§ To confirm the diagnosis of epilepsy
§ An adequate EEG should include a sleep and awake recording
§ To classify the seizure type
§ To make a diagnosis of non-‐convulsive status epilepticus
o Role of Interictal EEG in Epilepsy
§ Confirms clinical diagnosis of epilepsy § Classification of seizure types § Definition of Epileptic syndromes
• Monitoring of response to AED treatment • Evaluation of patients with single
seizures
§ Guide in the decision to discontinue AED treatment
ü BRAIN IMAGING (MRI or CT) o Indications:
§ Partial onset seizures at any age § Adult onset seizure of any type
§ Presence of focal neurologic deficit CT and MRI allow identification of structural lesions
• MRI higher specificity and sensitivity in diagnosing congenital brain anomalies, hippocampal sclerosis, AV malformations, tumors
• CT scan : if MRI is not available or in those with pacemakers. aneurysm clips, severe claustrophobia ü DIFFERENTIAL DIAGNOSES o Syncope/Faints o TIA o Drop attacks o Complicated migraine o Hypertensive emergency o Psychiatric disorders TREATMENT
ü CRITERIA FOR STARTING ANTIEPILEPTIC DRUG (AED)
o The diagnosis of epilepsy must be firm and definite o Risk of seizure recurrence must be sufficient
o Seizure type or epilepsy syndrome The AIM of Treatment with AEDs is to prevent seizures for the following reasons:
§ Prevent injury
§ Avoid disruption to employment or education § Minimize the social consequences of the
condition
§ Try to prevent status epilepticus WHEN TO REFER TO A SPECIALIST
o Need to confirm diagnosis o Poor seizure control o Severe/toxic side effects o Patients planning a pregnancy
o Seizure free patient considering drug withdrawal CAUSES OF RECURRENT SEIZURES IN DIFFERENT AGE
GROUPS (Adams, 19th Edition) • Neonates ü Congenital Maldevelopment ü Birth Injury ü Anoxia ü Metabolic Disorder - Hypocalcemia - Hypoglycemia - Vitamin B6 Deficiency - Biotinidase Deficiency - Phenylketonuria - Others • Infancy (1-‐6 months) ü As above
ü Infantile Spasms (West Syndrome)
• Early Childhood (6 months – 3 years) ü Infantile Spasms
ü Febrile Convulsions ü Birth Injury and Anoxia ü Infections
ü Trauma
ü Metabolic Disorders ü Cortical Dysgenesis ü Accidental Drug Poisoning
• Childhood (3—10 years) ü Perinatal Anoxia ü Injury at birth or later ü Infections
ü Thrombosis of Cerebral Arteries or Veins ü Metabolic Disorders
ü Cortical Malformations ü Lennox-‐Gastaut Syndrome ü “Idiopathic” (Probably Inherited) ü Rolandic Epilepsy
• Adolescence (10-‐18 years)
ü Idiopathic Epilepsy (Including genetically transmitted types)
ü Juvenile Myoclonic Epilepsy ü Trauma
• Early Adulthood (18-‐25 years) ü Idiopathic Epilepsy
ü Trauma ü Neoplasm
ü Withdrawal from alcohol or other sedative drugs
• Middle Age (35-‐60 years) ü Trauma
ü Neoplasm ü Vascular Disease
ü Alcohol or other drug withdrawal
• Late Life (Older than 60)
ü Vascular Disease (usually postinfarction) ü Tumor ü Abscess ü Degenerative Disease ü Trauma WHAT DRUG TO CHOOSE:
EFFICACY ESTABLISHED AED AGAINST COMMON SEIZURE DRUGS:
SEIZURE TYPE FIRST LINE SECOND LINE TONIC CLONIC Valproate
Carbamazepine Phenytoin
Lamotrigine
ABSENCE Valproate Ethosuximide
Lamotrigine
MYOCLONIC Valproate Topiramate Levetiracetam Zonisamide Partial Carbamazepine Phenytoin Valproate Lamotriging Oxcarbazepine Levetiracetam Drug Partia l Generaliz ed secondary Toni c Clon ic Absenc e Myoclon us Mixe d Carbamazep ine + + + x x o Clonazepam + + + ? ? + Phenobarbit al + + + o ? + ? Phenytoin + + + x x o Valproate + + + + + +
MEDICATION SIDE EFFECTS
Phenobarbital Sedation, sleepiness, hyperactivity, weakness
Dilantin –
Phenyhydantoin, Phenytoin
Dizziness, poor balance, weakness, thick gums, excessive hair growth, allergic rash, SJS
Tegretol – Carbamazepine
Allergic rash, dizziness, sleepiness, weakness, headache, gastric
discomfort, SJS, leukopenia, hyponatremia
Epival/Depakene Transient loss of appetite, alopecia, nausea, vomiting, weight gain
Rivotril – Clonazepam Sleepiness, weakness, in chidren – increase bronchial secretions
Trileptal – Oxcarbazepine
Headache, dizziness, sleepiness, nausea and hyponatremia
Neurontin – Gabapentin Sleepiness, fatigue, dizziness, weakness and rashes
Lamictal – Lamotrigine Allergic rash, drowsiness
Topamax Weight loss, mood changes, sleepiness, dizziness and kidney stones
-‐ start at the lowest computed appropriate dose and increase slowly until seizure control is achieved or side effects develop
-‐ Titrate slowly to allow tolerance to CNS side effects -‐ Keep the regimen simple wth OD-‐ BID dosing, if
possible
SURGICAL TREATMENT
-‐ temporal lobectomy-‐ 50% improvement in 5 years in complex partial seizures
-‐ Corpus callostomy – recommended for cotnrol of intractable partial and secondary generalized seizures – especially atonic drop attacks
-‐ Hemispherectomy – recommended for severe and extensive unilateral cerebral disease with intractable motor seizures and hemiplegia
o Rasmussens encephalitis, Sturge-‐Weber syndrome and Large porencephalic Cysts FACTORS RELATED TO SUCCESSFUL WIDTHRAWAL OF
AEDs -‐ Single type of lesion
-‐ Normal neurologic examination -‐ Normal IQ
-‐ Normal EEG following treatment COMPLICATIONS OF THE DISEASE:
-‐ STATUS EPILEPTICUS
o Recurrent generalized convulsions at a frequency that prevents regaining of conciousness in the interval between seizures o Prolonged convulsive status (longer than 30
mins.) carries high risk for serious neurologic sequelae (“epileptic encephalopathy”
o MANAGEMENT
Time in Minutes Standard
Treatment Proposed Treatment
0-‐5 Diagnosis and
assessment Lorazepam (1.0 mg/kg)
6-‐9 ABCs, Establish IV, Blood work, Give Thiamine and glucose Fosphenytoin (20 mg/kg PE) 10-‐20 Lorazepam (0.1 mg/kg) or Diazepam (0.2 mg/kg) 21-‐40 Phenytoin (15-‐ 20 mg/kg) Add phenytoind (5 gm/kg) / fosphenytoin (5 mg/kg) followed by Phenobarbital (20 mg/kg) or go to anesthesia 41-‐60 Add phenobarbital (5-‐10 mg/kg)
Greater than 60 Add phenytoin (5 mg.kg) x 2 followed by phenobarbital (20 mg/kg) followed by pentobarbital Anesthesia with Midazolam or Propofol
ROLE OF KETOGENIC AND MEDIUM CHAIN TRIGLYCERIDE DIET:
-‐ exact mechanism – UNKNOWN
-‐ chronic ketosis induced by a diet high in fat results in improvement of cerebral energetics and augmentation of GABA effects (?)
-‐ used mainly in children (1-‐10 years old)
-‐ 2/3 reduction in seizure frequency and reduction of AED usage
-‐ Effective in refractory epilepsy -‐ CHARACTERISTICS:
o Consists of daily regimen of 1g.kg protein o Enough fat to make up desired caloric
requirements
o Very small amount of carbs
o Ketogenic : antiketogenic potential ratio – 3:1 -‐ Caloric Distribution:
o Ketogenic – 87% fat, 6 % CHO and 7% CHON o MCT – 60% MCT, 11% fat, 19% CHO and 10%
CHON
o Thus more palatable and no increase in plasma cholesterol
