Transcript Epilepsy - Welcome to Selam Higher Clinic

Epilepsy
Subspecialty seminar
Oct 25, 2006
defn
Two or more unprovoked seizures.
 seizure is an abnormal electrical
activity of the brain due to hyper
synchronous firing of aggregates of
neurons.
CON
• Normally there are highly differentiated electrical
•
•
•
signals with in the brain that sustain the normal
life
“Electrical rebellion” that results in to
monotonous discharge firing in synchrony
across the brain
‘Sacire’ to take possession of
Most prevalent of the neurological disorders
Magnitude of the problem
• World wide incidence 0.3-.0.5%
prevalence 5-10/1000
• Ethiopia
prevalence 5.2/1000
GTC
81%
Partial complex 13.9
simple partial
5.7
The commonest of all neurological problems
Classification
• Partial and Generalized
• Partial when the seizure arises from discreet
area of the cortex
• Generalized when there is clinical or EEG
Manifestation of simultaneous i/v of both
hemispheres .
• Partial sz are common ones in adults
– Temporal lobe epilepsy commonest of the partials szs
Classification of Seizures
1. Partial seizures
a. Simple partial seizures (with motor,
sensory, autonomic, or psychic signs)
b. Complex partial seizures
c. Partial seizures with secondary
generalization
2. Primarily generalized seizures
a. Absence (petit mal)
b. Tonic-clonic (grand mal)
c. Tonic
d. Atonic
e. Myoclonic
3. Unclassified seizures
a. Neonatal seizures
b. Infantile spasms
Partial szs
• Simple partial no loss of consciousness
area involved →type of sz
Motor → convulsive
temporal →Auditory halln
→behavioral abn
limbic → Psychic
Post ictal paralysis 13.5%
Epilepsia partialis continua
JACKSONIAN march
•
Complex partial sz
•
•
•
•
•
•
•
Ass with alteration in consciousness
Stereotypical aura
Automatism
Post ictal confusion
Amnesia
Protean range of manifestations
Consider as DDx in any pt with paroxysmal
abnormal behavior esp if the pt seems not to be
fully aware of it
con
• Partial sz with sec generalizn
Aura sterotyped clear
Generalized szs
-Absence sz
Common in children
difficult to dx
easy to treat
transient lapses of consciousness
Subtle motor manifestations
70% remission rate
classic EEG findings
..con
Tonic clonic
the sterotype sz in the public mind
• the commonest sz of metabolic abnormalities
• 10% of the general popn at one time during their life
• Cx by: Loss of consciousness
tonic stiffning
clonic phase
Post ictal confusion
Headache/muscle pain
usually lasts for a minute
con
Tonic /Clonic szs
Atonic sudden loss of postural tone
predisposes to trauma
Consciousness briefly impaired
Myoclonic
brief reigonal or generalized contraction of the muscles
due to metabolic disturbance
Part of syndromes
Epilepsy syndromes
Juvenile myoclonic epilepsy
adolescents
benign
ass with other sz
Lennox Gastaut syd.
multiple sz
Cognitive abn
characterstic EEG
MTLE hippocampal sclerosis
partial complex sz
most studied
Mechanism
• Imbalance b/n excitation and inhibition of
the neuron
endogenous factor
Epileptogenic
PPting
…contd
• Epileptogenic HI,stroke,malignancies
infections,drugs..
• Endogenous family Hx
Genetic abnormalities
• PP factors sleep deprivation
photo
menses
Epileptogenesis refers to transformation of the
normal neuronal network in to that of chronically
hyperexcitable one
..con
Structural abnormalities
selective loss of neurones
(inhibitory or excitatory )
sprouting and reorganization
chronic hyperexcitable network
Con Partial
• Inhibitory neuronal loss
•
•
•
exicitatory neurons that stimulate the inhibitory
pathways are also lost
Abnormal integration of neurons with
reorganization
New neuron differentiation with formation of
new synapses
Alteration in the composition and expression of
GABA receptors
MTLE
…con
• Neuronal loss
• Reorganization
• Neurogenesis
gradually lowers
sz threshold
Mechanism
Absence
 Alteration in the circuitry b/n the thalamus
and the cortex
Normally the rhythm of cortical stimulation is
influenced by thalamus
The thalamocortical circuit underlies the
physiological cortical excitation including sleep
Either fires in a burst form or in a tonic manner
In turn it is influenced by the RAS
Thalamo cortical circuit
Mechanism
•
•
Developmental influences
Cortical malformations
proliferation
migration
cortical organization
Being identified using high resoln neuroimaging
• Change in the neuronal microenvironment
key buffering function
• Channelopathies
con
Focal Discreet lisions with disruption of
the balance
Generalized Network abnormalities
Intrinsic neuronal abnormalities
Evaluation
Is it a seizure?
 DDx for Sz
Does it have any reversible cause?
Is medication worth initiating?
HX preictal, ictal post ,ictal ,frequency
•
family hx
drugs
systemic illnesses
…Con
• pptin factors
• P/E look for atherosclerotic Markers
signs of trauma
skin abnormalities
neurological abn
LAB CBC,U/A, OFTs
electrolytes
LP
EEG
…CON
• Neuroimaging MRI/CT
•
functional studies
evaluation
Treatment
• Treat the underlying cause
• Treat the ppting factor
• Prevent recurrence
• Address psychosocial issues
General principles
•
•
•
•
•
•
•
•
The lower possible dose
Single drug
Appropraite for the type
Start low and go slow
depends on the frequency of the sz
Side effect profile
Drug interaction
Clinical monitoring
…con
• Serum drug levels
• Switch to another class of drug if not
controlled by one
• Use two drugs if single therapy of two
different classes fail
• Follow up acc the control of sz
• Issue of discontinuation
Antiepileptic drugs
 mode of action ion
channels/N.transmitters
 act on Na channels phenytoin,carbama
lamotrigine,topiramate
 Ca channel phenytoin
 GABA potentiation Barbiturates
 Glutamate uptake Lamotrigine
Primary
generalize
d
Partial
Absence
Atypical
absence,
myoclonic,
atonic
First line
Valproic acid
Lamotrigine
Carbamazepine
Phenytoin
Lamotrigine
Valproic acid
Valproic acid
Ethosuxamide
Valproic acid
Alternativ
e
Phenytoin
Carbamazepine
Topiramate
Zonisamide
Felbamate
Primidone
Phenobarbital
Topiramate
Levitracetam
Tiagabine
Zonisamide
Gabapentine
Primidone
Phenobarbital
Lamotrigine
Clonazepam
Lamotrigine
Topiramate
Clonazepam
Felbamate
New vs old drugs
• The new ones are found to be

as effective as those of the old

expensive

not time tested
Side effects of AEDS
Current recommendation
(American Academy Of Neurology)
Patients with newly diagnosed epilepsy
Who require treatment can be initiated on
standard AEDs such as carbamazepine,
valproic acid,phenobarbital
OR
The new AEDs
lamotrigine,gabapentin,oxcarbazine,or
topiramate
(evidence level A/B)
Status epilepticus
• Continues or repititive discreet szs without
regaining consciousness in between which
lasts 5 or more minutes
• Medical emergency
• As many statuses as epilepsies
• Ass with mortality rate of 20%
• The mechanism which normally aborts a
sz is lost
Etiology
• Drug discontinuation or incompliance
• Acute structural injuries
• Remote >>
abnormalities
• Metabolic abnormalities
• Drugs intoxications
…con
• Status is Cx by
1.
self sustenance
2.
Pharmaco-resistance
3.
Neuronal damage
Which tends to worsen as time passes without
Being controlled
Pathophysiology
• Milliseconds to secs
ionchannel opening/closing
Neurotransmitter modulation
• Secs to minutes
Receptor trafficing
• Minutes to Hrs
Plastic changes in neuropeptide modulators
• Hrs to days change in gene expression
partly explains how sz becomes self sustaining and
Pharmaco resistant
complications
• Hyperthermia
• Aspiration
• Rahbdomyolysis
• Lactic acidosis
• Brain injury
• Pulmonary edema
Treatment
• Supportive
Airways
BP
Fast neurological examn
Draw blood/secure iv line
• Ideal situations this should take <4’
• INITIATE Rx as fast as possible
Rx
…con
Diazepam/Lorazepm
IV stat
Repeat another dose
Secure 2nd iv line
Phenytoin 20mg/kg 50mg/min
10mg/kg
..cont.
Phenobarb 20mg/kg 50mg/min
Repeat 10mg/kg
If controlled taper for 24 hrs but maintain
higher serum levels
G/A Propofol
When the bp is low consider midazolam drip
.
References
Harrisons 16th edt
Uptudate 14.1
Lancet (vol 5 march 2006)
Nejm(349;13 sep 25,2003)
Nejm(2005,Tales of temporal lobe
www.neurology.com