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Seizures & Epilepsy. MBBS IV Group C Tutor: Prof. V. Wong 16 th Feb 2004. Outline. Definitions Pathophysiology Aetiology Classification Video demonstration Diagnostic approach Treatment Quiz . Definition. Seizure (Convulsion)

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Seizures & Epilepsy

MBBS IV Group C

Tutor: Prof. V. Wong

16th Feb 2004


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Outline

  • Definitions

  • Pathophysiology

  • Aetiology

  • Classification

  • Video demonstration

  • Diagnostic approach

  • Treatment

  • Quiz


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Definition

  • Seizure (Convulsion)

    • Clinical manifestation of synchronised electrical discharges of neurons

  • Epilepsy

    • Present when 2 or more unprovoked seizures occur at an interval greater than 24 hours apart


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Definition

  • Provoked seizures

    • Seizures induced by somatic disorders originating outside the brain

      • E.g. fever, infection, syncope, head trauma, hypoxia, toxins, cardiac arrhythmias


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Definition

  • Status epilepticus (SE)

    • Continuous convulsion lasting longer than 30 minutes OR occurrence of serial convulsions between which there is no return of consciousness

  • Idiopathic SE

    • Seizure develops in the absence of an underlying CNS lesion/insult

  • Symptomatic SE

    • Seizure occurs as a result of an underlying neurological disorder or a metabolic abnormality


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Aetiology of seizures

  • Epileptic

    • Idiopathic (70-80%)

    • Cerebral tumor

    • Neurodegenerative disorders

    • Neurocutaneous syndromes

    • Secondary to

      • Cerebral damage: e.g. congenital infections, HIE, intraventricular hemorrhage

      • Cerebral dysgenesis/malformation: e.g. hydrocephalus


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Aetiology of seizures

  • Non-epileptic

    • Febrile convulsions

    • Metabolic

      • Hypoglycemia

      • HypoCa, HypoMg, HyperNa, HypoNa

    • Head trauma

    • Meningitis

    • Encephalitis

    • Poisons/toxins


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Aetiology of Status Epilepticus

  • Prolonged febrile seizure

    • Most common cause

  • Idiopathic status epilepticus

    • Non-compliance to anti-convulsants

    • Sudden withdrawal of anticonvulsants

    • Sleep deprivation

    • Intercurrent infection

  • Symptomatic status epilepticus

    • Anoxic encephalopathy

    • Encephalitis, meningitis

    • Congenital malformations of the brain

    • Electrolyte disturbances, drug/lead intoxication, extreme hyperpyrexia, brain tumor


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Pathophysiology

  • Still unknown

  • Some proposals:

    • Excitatory glutamatergic synapses

    • Excitatory amino acid neurotransmitter (glutamate, aspartate)

    • Abnormal tissues — tumor, AVM, dead area

    • Genetic factors

    • Role of substantia nigra and GABA


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Pathophysiology

  • Excitatory glutamatageric synapses

  • And, excitatory amino acid neurotransmitter (glutamate, aspartate)

    • These are for the neuronal excitation

    • In rodent models of acquired epilepsy and in human temporal lobe epilepsy, there is evidence for enhanced functional efficacy of ionotropic N-methyl-D-aspartate (NMDA) and metabotropic (Group I) receptors

      Chapman AG. Glutatmate and Epilepsy. J Nutr. 2000 Apr; 130(4S Suppl): 1043S-5S


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Pathophysiology

  • Abnormal tissues — tumor, AVM, dead area

    • These regions of the brain may promote development of novel hyperexcitable synapses that can cause seizures


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Pathophysiology

  • Genetic factors

    • At least 20 %

    • Some examples

      • Benign neonatal convulsions--20q and 8q

      • Juvenile myoclonic epilepsy--6p

      • Progressive myoclonic epilepsy--21q22.3


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Pathophysiology

  • Role of substantia nigra

    • Studies with 2-deoxyglucose indicate that a marked increase in metabolic activity in SN is a common feature of several types of generalized seizures; it is possible that some of this increased activity is associated with GABAergic nerve terminals that become activated in an attempt to suppress seizure spread.

    • Because GABA has been shown to inhibit nigral efferents, it is likely that GABA terminals inhibit nigral projections that are permissive or facilitative to seizure propagation

      From Gale K. Role of the substantia nigra in GABA-mediated anticonvulsant actions. Adv Neurol.1986;44:343-364


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Pathophysiology

  • Premature brain

    • It is more susceptible to specific seizures than is the brain in older children and adults

  • Kindling

    • Repeated subconvulsive stimulation (e.g. to the amygdala) will lead to generalized convulsion

    • This may explain the development of epilepsy after injury to the brain

    • One temporal lobe seizure -> contralateral lobe



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Seizures

  • Partial

    • Electrical discharges in a relatively small group of dysfunctional neurones in one cerebral hemisphere

    • Aura may reflect site of origin

    • + / - LOC

Generalized

  • Diffuse abnormal electrical discharges from both hemispheres

  • Symmetrically involved

  • No warning

  • Always LOC


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Partial Seizures

Simple

Secondary generalized

Complex

1. w/ motor signs

2. w/ somato-sensory symptoms

3. w/ autonomic symptoms

4. w/ psychic symptoms

1. simple partial --> loss of consciousness

2. w/ loss of consciousness at onset

1. simple partial

--> generalized

2. complex partial

--> generalized

3. simple partial

--> complex partial

--> generalized


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Simple partial seizureswith motor signs

  • Focal motor w/o march

  • Focal motor w/ march

  • Versive

  • Postural

  • Phonatory


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Simple partial seizures with motor signs

  • Sudden onset from sleep

  • Version of trunk

  • Postural

    • Left arm bent

    • Forcefully stretched fingers

  • Looks at watch

  • Note seizure


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Simple partial seizures with sensory symptoms

  • Somato-sensory

  • Visual

  • Auditory

  • Olfactory

  • Gustatory

  • Vertiginous


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Simple partial seizures with sensory symptoms

  • Vertiginous symptoms

    “Sudden sensation of falling forward as in empty space”

  • No LOC

  • Duration: 5 mins


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Simple partial seizures with autonomic symptoms

  • Vomiting

  • Pallor

  • Flushing

  • Sweating

  • Pupil dilatation

  • Piloerection

  • Incontinence


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Simple partial seizures with autonomic symptoms

  • Stiffness in L cheek

  • Difficulty in articulating

  • R side of mouth is dry

  • Salivating on the L side

  • Progresses to tongue and back of throat


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Simple partial seizures with psychicsymptoms

  • Dysphasia

  • Dysmnesic

  • Cognitive

  • Affective

  • Illusions

  • Structured hallucinations


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Simple partial seizure with pyschic symptoms

  • Dysmnesic symptoms

    • “déjà-vu”

  • Affective symptoms

    • fear and panic

  • Cognitive

  • Structured hallucination

    • living through a scene of her former life again


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Complex Partial Seizures

  • Simple partial onset followed by impaired consciousness

    • with or without automatism

  • With impairment of consciousness at onset

    • with impairment of consciousness only

    • with automatisms


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Simple Partial Seizures followed by Complex Partial Seizures

  • Seizure starts from awake state

  • Impairment of consciousness

  • Automatisms

    • lip-smacking

    • right leg


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Complex Partial Seizures with impairment of consciousness at onset

  • Suddenly sit up

  • Roll about with vehement movement


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Partial Seizures evolving to Secondarily Generalised Seizures

  • Simple Partial Seizures to Generalised Seizures

  • Complex Partial Seizures to Generalised Seizures

  • Simple Partial Seizures to Complex Partial Seizures to Generalised Seizures


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Simple Partial Seizures to Generalised Seizures Seizures

  • Turns to his R with upper body and bends his L arm

  • Stretches body

  • LOC

  • Tonic-clonic seizure

  • Relaxation phase

  • Postictal sleep


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Simple Partial Seizures to Complex Partial Seizures to Generalised Seizures

  • Initially unable to communicate but understands

  • Automatism

    • Smacking

    • Hand-rubbing

  • Abolished communication

  • Generalised tonic-clonic seizure


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Generalized seizures Generalised Seizures

  • Absence

  • Myoclonic

  • Clonic

  • Tonic

  • Tonic-clonic

  • Atonic


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Absence seizures Generalised Seizures

  • Sudden onset

  • Interruption of ongoing activities

  • Blank stare

  • Brief upward rotation of eyes

  • Duration: a few seconds to 1/2 minute

  • Evaporates as rapidly as it started


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Absence seizures Generalised Seizures

  • Stops hyperventilating

  • Mild eyelid clonus

  • Slight loss of neck muscle tone

  • Oral automatisms


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Myoclonic seizures Generalised Seizures

  • Sudden, brief, shock-like

  • Predominantly around the hours of going to or awakening from sleep

  • May be exacerbated by volitional movement (action myoclonus)


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Myoclonic seizures Generalised Seizures

  • Symmetrical myoclonic jerks


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Clonic seizures Generalised Seizures

  • Repetitive biphasic jerky movements

  • Repetitive vocalisation synchronous with clonic movements of the chest (mechanical)

  • Venous injection of diazepam

  • Passes urine


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Tonic seizures Generalised Seizures

  • Rigid violent muscle contraction

  • Limbs are fixed in strained position

    • patient stands in one place

    • bends forward with abducted arms

    • deep red face

    • noises - pressing air through a closed mouth


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Tonic seizures Generalised Seizures

  • Elevates both hands

  • Extreme forward bending posture

  • Keeps walking without faling

  • Passes urine


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Tonic Phase Generalised Seizures

Sudden sharp tonic contraction of respiratory muscle: stridor / moan

Falls

Respiratory inhibition cyanosis

Tongue biting

Urinary incontinence

Clonic Phase

Small gusts of grunting respiration

Frothing of saliva

Deep respiration

Muscle relaxation

Remains unconscious

Goes into deep sleep

Awakens feeling sore, headaches

Tonic-clonic seizures(grand mal)


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Tonic-clonic seizures Generalised Seizures

  • Tonic stretching of arms and legs

  • Twitches in his face and body

  • Purses his lips and growls

  • Clonic phase


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Atonic seizures Generalised Seizures

  • Sudden reduction in muscle tone

  • Atonic head drop


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Epilepsy syndrome Generalised Seizures

  • Epilepsy syndromes may be classified according to:

    • Whether the associated seizures are partial or generalized

    • Whether the etiology is idiopathic or symptomatic/ cryptogenic

    • Several important pediatric syndromes can further be grouped according to age of onset and prognosis

  • EEG is helpful in making the diagnosis

  • Children with particular syndromes show signs of slow development and learning difficulties from an early age




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Three most common epilepsy syndromes:

  • Benign childhood epilepsy

  • Childhood absence epilepsy

  • Juvenile myoclonic epilepsy

    Three devastating catastrophic epileptic

    syndromes:

  • West syndrome

  • Lennox-Gastaut syndrome

  • Landau Kleffner Syndrome


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Benign childhood epilepsy with centrotemporal spike

(Benign Rolandic Epilepsy)

  • Typical seizure affects mouth, face, +/- arm. Speech arrest if dominant hemisphere, consciousness often preserved, may generalize especially when nocturnal, infrequent and easily controlled

  • Onset is around 3-13 years old, good respond to medication, always remits by mid-adolescence


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Childhood absence epilepsy

  • School age ( 4-10 years ) with a peak age of onset at 6-7 years

  • Brief seizures, lasting between 4 and 20 seconds

  • 3Hz Spike and wave complexes is the typical EEG abnormality

  • Sudden onset and interruption of ongoing activity, often with a blank stare.

  • Precipitated by a number of factors i.e. fear, embarrassment, anger and surprise. Hyperventilation will also bring on attacks.

    Juvenile myoclonic seizure

  • Around time of puberty

  • Myoclonic ( sudden spasm of muscles ) jerks → generalized tonic clonic seizure without loss of consciousness

  • Precipitated by sleep deprivation


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West’s syndrome (infantile spasms)

Triad:

  • infantile spasms

  • arrest of psychomotor development

  • hypsarrhythmia

  • Spasms may be flexor, extensor, lightning, nods, usually mixed. Peak onset 4-7 months, always before 1 year.

    Lennox-Gastaut syndrome

    Characterized by seizure, mental retardation and psychomotor slowing

    Three main type:

  • tonic

  • atonic

  • atypical absence

    Landau- Kleffner syndrome ( acquired aphasia )


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Diagnosis in epilepsy

  • Aims:

    • Differentiate between events mimicking epileptic seizures

      • E.g. syncope, vertigo, migraine, psychogenic non-epileptic seizures (PNES)

    • Confirm the diagnosis of seizure (or possibly associated syndrome) and the underlying etiology


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Diagnosis in epilepsy

  • Approach:

    • History (from patient and witness)

    • Physical examination

    • Investigations


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History

  • Event

    • Localization

    • Temporal relationship

    • Factors

    • Nature

    • Associated features

  • Past medical history

  • Developmental history

  • Drug and immunization history

  • Family history

  • Social history


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Physical Examination

  • General

    • esp. syndromal or non-syndromal dysmorphic features, neurocutaneous features

  • Neurological

  • Other system as indicated

    • E.g. Febrile convulsion, infantile spasm


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Investigations

  • I. Exclusion of differentials:

    • Bedside: urinalysis

    • Haematological: CBP

    • Biochemical: U&Es, Calcium, glucose, ABGs

    • Radiological: CXR, CT head

    • Toxicological: screen

    • Microbiological: LP

      (Always used with justification)


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Investigations

  • II. Confirmation of epilepsy:

    • Dynamic investigations : result changes with attacks

      • E.g. EEG

    • Static investigations : result same between and during attacks

      • E.g. Brain scan


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Electroencephalography (EEG)

  • EEG indicated whenever epilepsy suspected

  • Uses of EEG in epilepsy

    • Diagnostic: support diagnosis, classify seizure, localize focus, quantify

    • Prognostic: adjust anti-epileptic treatment



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Electroencephalography (EEG)

  • EEG interpretation in epilepsy

    • Hemispheric or lobar asymmetries

    • Periodic (regular, recurring)

    • Background activity:

      • Slow or fast

      • Focal or generalized

    • Paroxysmal activity:

      • Epileptiform features – spikes, sharp waves

      • Interictal or ictal

      • Spontaneous or triggered


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Electroencephalography (EEG)

  • Certain epilepsy syndromes have characteristic or suggestive features

  • E.g.


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Electroencephalography (EEG)

  • E.g. Brief absence seizure in an 18-year-old patient with primary generalized epilepsy


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Electroencephalography (EEG)

  • Note:

    • Normal in 10-20% of epileptic patients

    • Background slowed by:

      • AED, diffuse cerebral process, postictal state

    • Artifact from:

      • Eye rolling, tremor, other movement, electrodes

  • Interpreted in the light of proximity to seizure


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Neuroimaging

  • Structural neuroimaging

  • Functional neuroimaging


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Structural Neuroimaging

  • Who should have a structural neuroimaging?

    • Status epilepticus or acute, severe epilepsy

    • Develop seizures when > 20 years old

    • Focal epilepsy (unless typical of benign focal epilepsy syndrome)

    • Refractory epilepsy

    • Evidence of neurocutaneous syndrome


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Structural Neuroimaging

  • Modalities available:

    • Magnetic Resonance Imaging (MRI)

    • Computerized Tomography (CT)

  • What sort of structural scan?

    • MRI better than CT

    • CT usually adequate if to exclude large tumor

    • MRI not involve ionizing radiation

      • I.e. not affect fetus in pregnant women (but nevertheless avoided if possible)


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Functional Neuroimaging

  • Principles in diagnosis of epilepsy:

    • When a region of brain generates seizure, its regional blood flow, metabolic rate and glucose utilization increase

    • After seizure, there is a decline to below the level of other brain regions throughout the interictal period


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Functional Neuroimaging

  • Modalities available:

    • Positron Emission Tomography (PET)

    • Single Photon Emission Computerized Tomography (SPECT)

    • Functional Magnetic Resonance Imaging (fMRI)

  • Mostly used in:

    • Planning epilepsy surgery

    • Identifying epileptogenic region

    • Localizing brain function



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Seizure Therapy

Seizure

Specific Treatments

General Treatment

Reassurance and Education

Anticonvulsant

Surgery


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Education & Support

  • Information leaflets and information about support group

  • Avoidance of hazardous physical activities

  • Management of prolonged fits

    • Recovery position

    • Rectal diazepam

  • Side effects of anticonvulsants


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Anticonvulsants

  • Suppress repetitive action potentials in epileptic foci in the brain

    • Sodium channel blockade

    • GABA-related targets

    • Calcium channel blockade

    • Others: neuronal membrane hyperpolarisation


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Anticonvulsants

Drugs used in seizure disorders

Tonic-clonic and partial

Absence seizures

Myoclonic seizures

Status Epilepticus

Infantile Spasms

Cabamazepine

Ethosuximide

Corticotropin

Valproic acid

Short term control

Prolonged

therapy

Phenytoin

Valproic acid

Corticosteroids

Clonazepam

Valproic acid

Clonazepam

Diazepam

Phenytoin

Lorazepam

Phenobarbital


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Adverse Effects

  • Teratogenicity

    • Neural tube defects

    • Fetal hydantoin syndrome

  • Overdosage toxicity

  • Life-threatening toxicity

    • Hepatotoxicity

    • Stevens-Johnson syndrome

  • Abrupt withdrawal


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Medical Intractability

  • No known universal definition

  • Risk factors

    • High seizure frequency

    • Early seizure onset

    • Organic brain damage

  • Established after adequate drug trials

  • Operability


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Surgery

  • Curative

    • Catastrophic unilateral or secondary generalised epilepsies of infants and young children

      • Sturge-Weber syndrome

      • Large unilateral developmental abnormalities

  • Palliative

    • Vagal nerve stimulation


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Surgical Outcome

  • Medical Intractability

  • A well-localised epileptogenic zone

    • EEG, MRI

  • Low risk of new post-operative deficits


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References

  • Stedman’s Medical Dictionary.

  • MDConsult: Nelson’s textbook.

  • Illustrated Textbook of Pediatrics.

  • Video atlas of epileptic seizures – Classical examples, International League against epilepsy.

  • Guberman AH, Bruni J, 1999, Essentials of Clinical Epilepsy, 2nd edn. Butterworth Heinemann.

  • Manford M, 2003, Practical Guide to Epilepsy, Butterworth Heinemann.


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