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Seizures & Epilepsy
Prof.Mohammad Salah Abduljabbar
Outline
Definitions Pathophysiology Aetiology Classification Diagnostic approach Treatment Quiz
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.
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
Definition
Provoked seizures is a seizures induced by somatic disorders originating outside the brain
E.g. fever, infection, syncope, head trauma, hypoxia, toxins, cardiac arrhythmias
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 SESeizure develops in the absence of an underlying CNS lesion/insult
Symptomatic SESeizure occurs as a result of an underlying neurological disorder or a metabolic abnormality
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
Aetiology of seizures
Non-epileptic Febrile convulsions Metabolic
Hypoglycemia HypoCa, HypoMg, HyperNa, HypoNa
Head trauma Meningitis Encephalitis Poisons/toxins
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
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)
Pathophysiology
Still unknownSome proposals:
Excitatory glutamatergic synapses Excitatory amino acid neurotransmitter
(glutamate, aspartate) Abnormal tissues — tumor, AVM, dead
area Genetic factors Role of substantia nigra and GABA
Pathophysiology
Excitatory glutamatageric synapsesAnd, 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
Pathophysiology
Abnormal tissues — tumor, AVM, dead area These regions of the brain may promote
development of novel hyperexcitable synapses that can cause seizures
Pathophysiology
Genetic factors At least 20 % Some examples
Benign neonatal convulsions. Juvenile myoclonic epilepsy. Progressive myoclonic epilepsy.
Classification of seizures
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.
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
Simple Complex
Partial Seizures
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
Secondary generalized
1. simple partial --> generalized
2. complex partial--> generalized
3. simple partial --> complex partial--> generalized
Focal (partial) seizures Simple partial seizures
Motor, sensory, vegetative or psychic symptomato- logy
Typically consciousness is preserved
Simple partial seizureswith motor signs
Focal motor w/o march Focal motor w/ march Versive Postural Phonatory
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
Simple partial seizures with sensory symptoms
Somato-sensoryVisualAuditoryOlfactoryGustatoryVertiginous
Simple partial seizures with sensory symptoms
Vertiginous symptoms“Sudden sensation of
falling forward as in empty space”
No LOC Duration: 5 mins
Simple partial seizures with autonomic symptoms
VomitingPallorFlushingSweatingPupil dilatationPiloerection Incontinence
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
Simple partial seizures with psychic symptoms
DysphasiaDysmnesicCognitiveAffective IllusionsStructured hallucinations
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
Complex Partial SeizuresSimple partial onset followed by
impaired consciousness with or without automatism
With impairment of consciousness at onset with impairment of consciousness only with automatisms
Partial Seizures evolving to Secondarily Generalized
Seizures
Simple Partial Seizures to Generalised Seizures
Complex Partial Seizures to Generalised Seizures
Simple Partial Seizures to Complex Partial Seizures to Generalised Seizures
Generalized seizures
AbsenceMyoclonicClonicTonicTonic-clonicAtonic
Generalized seizures(convulsive or non-convulsive)
Absences Myoclonic seizures Clonic seizures Tonic seizures Atonic seizures
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
Absence seizures Stops
hyperventilating Mild eyelid clonus Slight loss of neck
muscle tone Oral automatisms
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)
Myoclonic seizures
Symmetrical myoclonic jerks
Clonic seizures
Repetitive biphasic jerky movements
Repetitive vocalisation synchronous with clonic movements of the chest (mechanical)
Venous injection of diazepam
Passes urine
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
Tonic seizures
Elevates both hands Extreme forward
bending posture Keeps walking
without faling Passes urine
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
Tonic-clonic seizures
Tonic stretching of arms and legs
Twitches in his face and body
Purses his lips and growls
Clonic phase
Atonic seizures
Sudden reduction in muscle tone
Atonic head drop
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
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)
Table 1. Modified ILAE Classification of Epilepsy Syndromes
Special syndromes Febrile convulsionsSeizures occurring only with toxic or metabolic provoking factorsNeonatal seizures of any etiologyAcquired epileptic aphasia (Landau-Kleffner syndrome)
Table 1. Modified ILAE Classification of Epilepsy Syndromes
(cond’)
Three most common epilepsy syndromes:1. Benign childhood epilepsy2. Childhood absence epilepsy3. Juvenile myoclonic epilepsy
Three devastating catastrophic epileptic syndromes:1. West syndrome 2. Lennox-Gastaut syndrome 3. Landau Kleffner Syndrome
Benign childhood epilepsy with centrotemporal spike
(Benign Rolandic Epilepsy)
1. Typical seizure affects mouth, face, +/- arm. Speech arrest if dominant hemisphere, consciousness often preserved, may generalize especially when nocturnal, infrequent and easily controlled
2. Onset is around 3-13 years old, good respond to medication, always remits by mid-adolescence
Childhood absence epilepsy1. School age ( 4-10 years ) with a peak age of onset at 6-7
years2. Brief seizures, lasting between 4 and 20 seconds3. 3Hz Spike and wave complexes is the typical EEG abnorm
ality
4. Sudden onset and interruption of ongoing activity, often with a blank stare.
5. Precipitated by a number of factors i.e. fear, embarrassment, anger and surprise. Hyperventilation will also bring on attacks.
Juvenile myoclonic seizure 1. Around time of puberty2. Myoclonic ( sudden spasm of muscles ) jerks →
generalized tonic clonic seizure without loss of consciousness
3. Precipitated by sleep deprivation
West’s syndrome (infantile spasms)Triad: 1. infantile spasms2. arrest of psychomotor development3. 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:1. tonic2. atonic3. atypical absence
Landau- Kleffner syndrome ( acquired aphasia )
Diagnosis in epilepsyAims:
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
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
Diagnosis in epilepsyApproach:
History (from patient and witness) Physical examination Investigations
History Event
Localization Temporal relationship Factors Nature Associated features
Past medical history Developmental history Drug and immunization history Family history Social history
Physical ExaminationGeneral
esp. syndromal or non-syndromal dysmorphic features, neurocutaneous features
NeurologicalOther system as indicated
E.g. Febrile convulsion, infantile spasm
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)
Investigations I. Exclusion of differentials:
Bedside: urinalysis Hematological:CBP Biochemical: U&Es, Calcium, glucose, ABGs Radiological: CXR, CT head Toxicological: screen Microbiological: LP (Always used with justification)
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
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
International 10-20 System of Electrode Placement in EEG
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
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 <2.5 Hz
Electroencephalography (EEG)
E.g. Brief absence seizure in an 18-year-old patient with primary generalized epilepsy
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
NeuroimagingStructural neuroimagingFunctional neuroimaging
Structural NeuroimagingWho 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
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)
Functional NeuroimagingPrinciples 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
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
Venn Diagram
Seizure Therapy
Anticonvulsant Surgery
Specific Treatments
Reassurance and Education
General Treatment
Seizure
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
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…
Treatment 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.
Anticonvulsants
Suppress repetitive action potentials in epileptic foci in the brain Sodium channel blockade GABA-related targets Calcium channel blockade Others: neuronal membrane
hyperpolarisation
Anticonvulsants
CabamazepinePhenytoin
Valproic acid
Tonic-clonic and partial
EthosuximideValproic acidClonazepam
Absence seizures
Valproic acidClonazepam
Myoclonic seizures
DiazepamLorazepam
Short term control
PhenytoinPhenobarbital
Prolonged therapy
Status Epilepticus
CorticotropinCorticosteroids
Infantile Spasms
Drugs used in seizure disorders
Adverse EffectsTeratogenicity
Neural tube defects Fetal hydantoin syndrome
Overdosage toxicityLife-threatening toxicity
Hepatotoxicity Stevens-Johnson syndrome
Abrupt withdrawal
Medical Intractability
No known universal definition Risk factors
High seizure frequency Early seizure onset Organic brain damage
Established after adequate drug trials
Operability
SurgeryCurative
Catastrophic unilateral or secondary generalised epilepsies of infants and young children
Sturge-Weber syndrome Large unilateral developmental
abnormalities
Palliative Vagal nerve stimulation
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 amygdalohippocampectomy, extensive lesionectomy, cortical resection, hemispherectomy.
Palliative procedures: Corpus callosotomy and Vagal nerve stimulation (VNS).
Surgical Outcome
Medical IntractabilityA well-localised epileptogenic zone
EEG, MRILow risk of new post-operative
deficits
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.
References
1. Stedman’s Medical Dictionary.2. MDConsult: Nelson’s 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.