Seizures

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Seizures Epilepsy

• Prof.Mohammad Salah Abduljabbar

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Outline

• Definitions
• Pathophysiology
• Aetiology
• Classification
• Diagnostic approach
• Treatment
• Quiz

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Definition

• A chronic neurologic disorder manifesting by
  repeated epileptic seizures (attacks or fits)
  which result from paroxysmal uncontrolled
  discharges of neurons within the central nervous
  system (grey matter disease).
• The clinical manifestations range from a major
  motor convulsion to a brief period of lack of
  awareness. The stereotyped and uncontrollable
  nature of the attacks is characteristic of
  epilepsy.

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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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Pathogenesis

• The 19th century neurologist Hughlings Jackson
  suggested a sudden excessive disorderly
  discharge of cerebral neurons as the causation
  of epileptic seizures.
• Recent studies in animal models of focal epilepsy
  suggest a central role for the excitatory
  neurotransmiter glutamate (increased) and
  inhibitory gamma amino butyric acid (GABA)
  (decreased)

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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.
• Juvenile myoclonic epilepsy.
• Progressive myoclonic epilepsy.

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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.198644343-364

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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 -gt contralateral lobe

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Classification of seizures
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Epilepsy - Classification

• The modern classification of the epilepsies is
  based upon the nature of the seizures rather than
  the presence or absence of an underlying cause.
• Seizures which begin focally from a single
  location within one hemisphere are thus
  distinguished from those of a generalised nature
  which probably commence in a deeper structures
  (brainstem? thalami) and project to both
  hemispheres simultaneously.

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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 --gt loss of consciousness 2.
w/ loss of consciousness at onset
1. simple partial --gt generalized 2. complex
partial --gt generalized 3. simple partial --gt
complex partial --gt generalized
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Focal (partial) seizures

• Simple partial seizures
• Motor, sensory, vegetative or psychic
  symptomato- logy
• Typically consciousness is preserved

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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 psychic symptoms

• 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

• 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

• Absence
• Myoclonic
• Clonic
• Tonic
• Tonic-clonic
• Atonic

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Generalized seizures(convulsive or
non-convulsive)

• Absences
• Myoclonic seizures
• Clonic seizures
• Tonic seizures
• Atonic seizures

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Absence 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

• Stops hyperventilating
• Mild eyelid clonus
• Slight loss of neck muscle tone
• Oral automatisms

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Myoclonic 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

• Symmetrical myoclonic jerks

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Clonic 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

• 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

• Elevates both hands
• Extreme forward bending posture
• Keeps walking without faling
• Passes urine

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Tonic-clonic seizures(grand mal)

• Tonic Phase
• 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

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Tonic-clonic 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

• Sudden reduction in muscle tone
• Atonic head drop

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Epilepsy syndrome

• 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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Table 1. Modified ILAE Classification of Epilepsy
Syndromes
Category Localization-related Generalized
Idiopathic Benign epilepsy of childhood with centrotemporal spikes(benign rolandic epilepsy)Benign occipital epilepsy Benign myoclonic epilepsy in infancyChildhood absence epilepsyJuvenile absence epilepsyJuvenile myoclonic epilepsy
Symptomatic (of underlying structural disease) Temporal lobeFrontal lobeParietal lobeOccipital lobe Early myoclonic encephalopathyCortical dysgenesisMetabolic abnormalitiesWest syndromeLennox-Gastaut syndrome
Cryptogenic Any occurrence of partial seizures without obvious pathology Epilepsy with myoclonic absencesWest syndrome (with unidentified pathology)Lennox-Gastaut syndrome (with unidentified pathology)
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Table 1. Modified ILAE Classification of Epilepsy
Syndromes (cond)
Special syndromes Febrile convulsionsSeizures occurring only with toxic or metabolic provoking factorsNeonatal seizures of any etiologyAcquired epileptic aphasia (Landau-Kleffner syndrome)
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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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• Wests 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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Epilepsy Differential Diagnosis

• The following should be considered in the diff.
  dg. of epilepsy
• Syncope attacks (when pt. is standing results
  from global reduction of cerebral blood flow
  prodromal pallor, nausea, sweating jerks!)
• Cardiac arrythmias (e.g. Adams-Stokes attacks).
  Prolonged arrest of cardiac rate will
  progressively lead to loss of consciousness
  jerks!
• Migraine (the slow evolution of focal hemisensory
  or hemimotor symptomas in complicated migraine
  contrasts with more rapid spread of such
  manifestation in SPS. Basilar migraine may lead
  to loss of consciousness!
• Hypoglycemia seizures or intermittent
  behavioral disturbances may occur.
• Narcolepsy inappropriate sudden sleep episodes
• Panic attacks
• PSEUDOSEIZURES psychosomatic and personality
  disorders

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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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Epilepsy Investigation

• The concern of the clinician is that epilepsy may
  be symptomatic of a treatable cerebral lesion.
• Routine investigation Haematology, biochemistry
  (electrolytes, urea and calcium), chest X-ray,
  electroencephalogram (EEG).
• Neuroimaging (CT/MRI) should be performed in all
  persons aged 25 or more presenting with first
  seizure and in those pts. with focal epilepsy
  irrespective of age.
• Specialised neurophysiological investigations
  Sleep deprived EEG, video-EEG monitoring.
• Advanced investigations (in pts. with intractable
  focal epilepsy where surgery is considered)
  Neuropsychology, Semiinvasive or invasive EEG
  recordings, MR Spectroscopy, Positron emission
  tomography (PET) and ictal Single photon emission
  computed tomography (SPECT)

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Investigations

• I. Exclusion of differentials
• Bedside urinalysis
• Haematological CBP
• Biochemical UEs, 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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International 10-20 System of Electrode Placement
in EEG
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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.

Infantile spasms Hypsarrhythmia
Childhood absence epilepsy Generalized 3-Hz spike-wave
Juvenile myoclonic epilepsy Generalized/ multifocal 4-5 Hz spike-wave and polyphasic-wave
Benign occipital epilepsy Unilateral/ bilateral occipital sharp/ sharp-slow activity that attenuates on eye opening
Lennox-Gastaut syndrome Generalized/ bianterior spike-wave activity at lt2.5 Hz
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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 gt 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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Venn Diagram
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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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Epilepsy - Treatment

• The majority of pts respond to drug therapy
  (anticonvulsants). In intractable cases surgery
  may be necessary. The treatment target is
  seizure-freedom and improvement in quality of
  life!
• The commonest drugs used in clinical practice
  are Carbamazepine, Sodium valproate, Lamotrigine
  (first line drugs) Levetiracetam, Topiramate,
  Pregabaline (second line drugs) Zonisamide,
  Eslicarbazepine, Retigabine (new AEDs)
• Basic rules for drug treatment Drug treatment
  should be simple, preferably using one
  anticonvulsant (monotherapy). Start low,
  increase slow. Add-on therapy is
  necessary in some patients

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Epilepsy Treatment (cont.)

• If pt is seizure-free for three years, withdrawal
  of pharmacotherapy should be considered.
  Withdrawal should be carried out only if pt is
  satisfied that a further attack would not ruin
  employment etc. (e.g. driving licence). It should
  be performed very carefully and slowly! 20 of
  pts will suffer a further sz within 2 yrs.
• The risk of teratogenicity is well known (5),
  especially with valproates, but withdrawing drug
  therapy in pregnancy is more risky than
  continuation. Epileptic females must be aware of
  this problem and thorough family planning should
  be recommended. Over 90 of pregnant women with
  epilepsy will deliver a normal child.

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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

83
Surgery

• Curative
• Catastrophic unilateral or secondary generalised
  epilepsies of infants and young children
• Sturge-Weber syndrome
• Large unilateral developmental abnormalities
• Palliative
• Vagal nerve stimulation

84
Epilepsy Surgical Treatment

• A proportion of the pts with intractable epilepsy
  will benefit from surgery.
• Epilepsy surgery procedures Curative (removal of
  epileptic focus) and palliative (seizure-related
  risk decrease and improvement of the QOL)
• Curative (resective) procedures Anteromesial
  temporal resection, selective amygdalohippocampect
  omy, extensive lesionectomy, cortical resection,
  hemispherectomy.
• Palliative procedures Corpus callosotomy and
  Vagal nerve stimulation (VNS).

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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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Status Epilepticus

• A condition when consciousness does not return
  between seizures for more than 30 min. This state
  may be life-threatening with the development of
  pyrexia, deepening coma and circullatory
  collapse. Death occurs in 5-10.
• Status epilepticus may occur with frontal lobe
  lesions (incl. strokes), following head injury,
  on reducing drug therapy, with alcohol
  withdrawal, drug intoxication, metabolic
  disturbances or pregnancy.
• Treatment AEDs intravenously ASAP, event.
  general anesthesia with propofol or thipentone
  should be commenced immediately.

87
References

1. Stedmans Medical Dictionary.
2. MDConsult Nelsons textbook.
3. Illustrated Textbook of Pediatrics.
4. Video atlas of epileptic seizures Classical
   examples, International League against epilepsy.
5. Guberman AH, Bruni J, 1999, Essentials of
   Clinical Epilepsy, 2nd edn. Butterworth
   Heinemann.
6. Manford M, 2003, Practical Guide to Epilepsy,
   Butterworth Heinemann.