Seizure new onset

New onset seizure in adults
-A review article
Jay R. Gavvala.MD, Stephan U.Schule .MD.Journal of american medical association , volume 316, number 24, page 2657

• Jay R. Gavvala.MD, Stephan U.Schule .MD.
• Journal of american medical association , volume 316, number 24, page 2657
• JAMA. 2016;316:2657-2668.DOI10.1001/JAMA .2016.18625
• Impact factor Journal Of American Medical Association 37.684
• Impact factor of The Lancet journal 44.006
• Impact factor The British Medical Journal 19.974
.Journal of American Medical Association , volume 316, number 24, page 2657
2

Methods
• Review aricles , primary literature, metaanalysis were included
in this study
• 1976 to 2016
• And the articles were rated using oxford centre for evidence
based medicine 2009
• Grade A- best level of evidence
• Grade D – poor level of evidence
.Journal of American Medical Association , volume 316,
number 24, page 2657
3

Aim of the Article….
• To clear the doubts regarding definition of epilepsy
• Systematic Approach to new onset seizures
• Order of the investigations to be done as well as the sensitivity
and specificity of those investigations .
• Beginnining of therapy.
• Continuation or cessation of therapy.
• Response rates to the individual drugs, specific considerations,
comparative trials.
4

EPIDEMIOLOGY
5

Article index
• Introduction –Definitions & Distinguish
• Methods
• Results
 Clinical presentation
 Epidemiology
 Risk factors for epilepsy
 Assessment and diagnosis – histiory,imaging,eeg,chemistry,prolactin, lumbarpuncture
• Risk of seizure recurrence – unprowoked / prowoked
• Treatment – choice of antiepileptic
• Response rates
• Patient counselling
• Prognosis and duration of therapy
• Discussion
• Conclusion .Journal of American Medical Association , volume 316,
6

Introduction
• Seizure – a transient occurance of signs and symptoms due to abnormal excessive or
synchronus neuronal activity in brain
• Unprowokwed seizure
• Acute symptamatic seizure – in close temporal association with a transient central
nervous system or systemic insult presumed to be an acute manifestation of the insult
• Focal seizure – one part of cerebral hemisphere
• Generalised seizure – rapidly engaging networks distributing in bilateral hemispheres
7

Epilepsy..
Disorder of the brain characterised by an enduring predisposition to generarate
epileptic seizures i.e.
2 or more un provoked seizures occuring more than 24 hours apart
or
One un provoked seizure and a high risk ( at least 60 % ) of recurrent un
provoked seizures over the next 10 years
8

Patient with ……
9

• Rapid onset of negative symptoms such as numbness,weakness,aphasia
• Typically not a/w stiffening/ jerking
• Resulting from temporary interruption of bllod supply in the
distrriibution of certebral vessel
Transient Ischaemic Attack
10

• Unilateral pulsating head ache , aura , nausea . vomitting
• Some times isolated, neurological symptoms without head ache .
• Duration of sisease typically lasting hours to days with a slow progression of
aura and neurological deficit.
Typical or atypical migraine
11

• A transient loc with complete return to preexisting neuroogical function
• Some times triggered by, fear, pain, medical procedures, coughing, micturition,
defecation or valsalva maneuver
• Some tomes due to orthostasis – in case of hypovolemia and underlying sructural
heart disease
Syncope / vasovagal syncope
12

• Abnormal body movements
• Trigger being emotional events or stressors
• Lasting longer than epileptic seizure with waxing and wanindg
quality
• Eye closure , pelvic thrusting , vocal stuttering . partial awareness
Psychogenic non epileptic seizure
13

• Start with aura
• Loss of awareness
• Unilateral sensations
• Unilateral Motor activity
• Faster than migraine symptoms
Focal seizure
14

• No warning
• Sudden generalised tonic – clonic activity
• Some tomes brief staring looks
• Myoclonic jerks
Generalised seizure
15

CLINICAL PRESENTATION
• Always think that event was epileptic and rule out then proceed
• Clinical history- recollection , awareness and experience
• Any witnesses, if so , enquire seperately.
• Age of onset / family history
• Excessive sleep deprivation
• Alcohol / illicit drugs
• Certain medication that dicrease the seizure threshold- Clozapine ,
Cephalosporins, Fluoroquinolones , Bupropion, Tramadol.
• Metabolic derangement abg
• Toxin exposure
• Head injury / prior neurological disease or surgeries.
16

• Description of all relevant physical examination findings and
classification is beyond the scope
• Lateral tongue bite - 22% of patients with all types of epileptic
seizures.
• Bruces , back pain , compression fractures
• Nuchal rigidity or asterexis – s/o underlying systemic disorder that may
have caused the acute symtmatic seizure
• Skin – signs of Neurofibromatosis , Tuberous Sclerosis, Sturge Weber
Syndrome
17

BRAIN IMAGING
• First seizure – Neuroimaging is must
• Uncertainity remains regarding appropriate timing and type of
imaging ( grade b )
• Earier studies – CT Was The Modality – 10% of new onset
seizure had abnormality in CT
• Mri – abnormality detection increased to 30%
18

• New neuro deficit
• persistent alterd mental status
• recent trauma and prolonged head ache
 Urgent Imaging
19

• CT is the usual first imaging modality.
• Lesions which are missed on CT
Low grade glioma
Hippocampal sclerosis
Cavernous malformation
Cortical dysplasia
Periventricular heterotopias
20

AN EPILEPSY PROTOCOL- SPECIFIC BRAIN
MRI
• 1 -3 mm slices
• Coronal fluid attenuated inversion recovery sequences
• Best for focal cortical dysplasias , hippocampal sclerosis
• Presence of abnormalities
risk recurrence becomes 60 %
 defines epilepsy
21

Electro encephalography
• New onset seizure , but not returning to base line within 30 to 60 minutes after end of the
seizure or waxing and waning level of conciousness or have a focal dysfunction un explained
by a structural lesion
 CONTINUOUS EEG .
• Subclinical seizures or acute brain inury or altred mental status persisting
 LESS THAN 50 % ARE DETECTED BY 30 MIN OF EEG(GRADE B)
22

• But 90 % are detected by 24 to 36 hours of continuous eeg
monitoring
• New onset seizure = 29% will epileptiform changes on first eeg
• Detection rate is better in opd pateints than in ipd.
23

CHEMISTRY PANEL
• ROUTINE SCREENING IS PROPOSED IN NEW ONSET SEIZURES FOR
Hypoglycemia
Uremia
drug intoxication
Hyponatremia
Grade d
Harldly 4 % have these abnormalities
24

PROLACTIN LEVEL
• It is actually comparison of the prolactin after seizure and base line
prolactin at least before 6 hours of the seizure event
• If already pretest probability of developing seizure is 50 % then
only proactin shows 93% sensitivity
25

• To differentiaate from psychogenic seizures can be used .
(Gradeb )
• Impracical due to base line measurmemnts not possible
• Cannot differentiate btw sycope and seizure
• Low sensitivity and low negative predictive value ( grade a )
26

Lumbar puncture
• In view of
• Meningitis
• Encephalitis
• SAH
• Lp in new onset sz has (grade d)
• 8 % of patients had a clinically significant findings
27

POSSIBLE NEW ONSET SZR
28
IS THE EVENT DECRIPTION AND
WITNESS S/O SZR ??
Is yes , take history and
perform a physical
examination
If no, look for ,
migrain , tia , syncope
Fever , focal deficit or mental
status change ??

29
If no fever / altered mental status , look for
evidence provoking factors (sleep deprivation ,
alcohol use , drugs ) ?
If yes , urgent evaluation for acute symptamatic seizure
Lab testing
Urgent CT
And or MRI
Urgent EEG / continuos EEG
Manage as in patient admission

30
If presence of provoking factors , non urgennt evaluation for acute symptamatic
seizure , work up,
Lab testing
Brain CT
Out patient EEG
Management
life style modification ,
defer anti epileptic medication
If no, then its unprovoked seizure
Do, EEG
Epilepsy protocol MRI

Risk of seizure recurrence
Un provoked seizures
35 % chance of recurrence within 5 years following new onset
seizures
Second seizure occurance = 75 % in 5 years
Higher risk of recurrence in patients with
 Abnormal brain imaging (grade b )
 Eeg positive ( grade a )
 Nocturnal seizure ( grade b )
 Seizures attributed to prior brain injury ( grade a)
31

32

Acute symptamatic seizures( provoked seizures)
• Lower risk of subsequent un provoked seizures
• In acute brain insults 10-20% risk of recurrence
• Acute brain insults – closed head injury , acute hemorrhagic ir
ischemic stroke , sah , brain surgery , cns infections.
• Eeg with abormality increases risk of recurrence , but cannot
predict the future risk of unprovoked seizure
33

TREATMENT
• Points to considered
 Risk of recurrence
 Seizure type
 Etiology
 Suitable choice of antiepileptic with limitted adverse effects
 Anticipated duration of medication
 Consider the time to therapeutic onset of antiepileptic drug , to eliminate the frequent
seizure and to decide the dose before discharge from hospital.Journal of American Medical Association , volume 316,
34

TREATMENT ALGORITHM IN PATIENTS
WITH NEW ONSET EPILEPSY
35

Individuals with new onset epilepsy
one seizure + abnormal eeg / mri or
two seizure
36
FOCAL EPILEPSY - BEGIN ANTI EPILEPTIC
Narrow spectrum – carbamazepine , oxcarbamazepine , phenytoin , lacosamide or
Broad spectrum –lamotrigine , levitiracetam , topiramate , valproate , zonisamide

• GENERALISED EPILEPSY OR UNKNOWN EPILEPSY TYPE
BEGIN BROAD SPECTRUM ANTIEPILEPTIC MEDICATION ( CHOICE
DEPENDS ON SEIZURE TYPE )
lamotrigine , levitiracetam , topiramate , valproate , zonisamide
37

Titrate to therapeutic dose
38
Is the patient still having seizures?
If no, continue curent treatment untill seizure free for atleast 2 years
If yes , add a second medication ( dual therapy ) or taper then
discontinue first medication while adding a second medication

Do the seizure persists ?
• If yes , revisit diagnosis for seizure that persists for > 1 year ,
consider epilepsy monitiring unit admission
39
If no, continue treatment , either as mono therapy or dual
therapy untill seizure free atleast for 2 years

• In case of insufficient evidence to prove focal seizures , use
broad spectrum drugs
40
QUICK ONSET OF ACTION
Lacosamide
Phenytoin
Levitiracetam
valproate

CAUTION
• Phenytoin and carnamazepine cyp 450 inducers
• Valproate – enzyme inhibitor
• Patients with muliple co morbodities , like taking warfarin or
chemotherapeutic agents use – lamotrigine, levitiracetam,
lacosamide
• Rft , lft must before prescribing the anti epileptics
41

GENERIC FORMULATIONS
• Seizure control and adrs effects vary with various generic
formulations
• But recent studies shows very less variation at plasm drug
concentartion level and one can switch over the generic and
brand names
42

COMPARATIVE TRIALS
• Older drugs like phenytoin and carbamazepine have higher success
ratesin treatment but side effects are more with phenytoin( grade a)
• Carbamazepine = valproate in treatment of focal seizures evolving
into bilateral convulsive seizures.
• Carbamazepine has fewer side effects
43

• Lamotrigine = Oxcarbamazepine= Carbamazepine In Efficacy
In Focal Szr Treatment
• Tolerance Wise Lamotrigine >Oxcarbamazepine=
Carbamazepine ( Grade A ) In Focal Szr Treatment
44

• In generalised epilepsies , valproate Is more efficaccious than
lamotrigine and better tolerated than topiramate ( grade a )
• Recent studies , levitiracetam and zonisamide to be both
efficacious and well tolerated in both focal and generalised
epilepsy
45

Adverse effects
• Individuals with first time anti epileptic drugs , side effects
were seen in 7 to 31 % of all patients
• Poly therapy = 88 % cance of developing adrs
• Adrs – somnoloscence , dizziness, blurry vision , difficulties
with cincentration and memory
46

• Adrs are dose dependent and are prominent during first few
days of therapy
• Dose should be slowly escalated and minimum dose with
frequent administration
47

• All antiepileptics can cause , rash raning from maculopapular variety
to TEN and SJ syndrome( 1 -10 / 10000)
• Most common are – phenytoin , carbamazepine, lamotrigine
• Risk of TEN OR SJ more commonly seen in first 60 days of initiation
of therapy
• HLA B 15.02ALLELES are more prone for SJ OR TEN – in asians
om CBZ and phenytoin  FDA says , madatory screning before CBZ
48

49

ANTIEPILEPTICS IN FEMALES
• Teratogenicity and intreraction with cintraception should be
considered.
• Enzyme inducers  failure of contraceptives
• OC pills dicrease the plasma concentration of lamotrigine
• IUD are best for contraception
50

• Valproate is teratogenic – 10 % risk of major congenital anomalies.
Also lower iq in born child
• Congenital malformation also seen with –phenobarbital , topiramate
, phenytoin and carbamazepine , levitiracetam and lamotrigine also
exhibit the risk
• Lacosamide and oxcarbamazepine showse limited teratogenecity
51

Antiepileptics in older patients
• Lamotrigine and gabapentin = good efficacy , less side effects (
limitted literature )
• Levitiracetam > cbz or valproic acid
52

Response rates
• Early initiatiation of therapy in new onset szr , only delayes the 2nd
episode of seizure but long term prognosis remains the same .( grade a)
• Diagnosed epilepsy after two or more un provoked seizures ,
50 % will become seizure with single apprppriate drug
13 % will be seizure free with second drug addition
4 % with 3 rd drug
• Declining prognosis with additon as severity increasing
53

Counselling
• Known fact
• 15 – 19 times risk of death by drowning compared to general
population.
• Non commercial driving can be allowed 6 months after un
provoked seizure and 3 months after acute symptamatic seizure.
• Commercial driving only after 2 to 5 years of seizure free interval.
54

DURATION OF THERAPY
• Free of seizure for 2 years with antiepileptics and normal
neurological examination then after withdrawl of drug 59 %
remained seizure free for next 2 years ( grade a )
55

• Seizure free period of less than 4 years before withdrawl ang
longer duration of active epilepsy that is not started treatment
are independent risk factors for relapse.
• Highest risk of relapse = within 2 yrs of withdrawl
• < 1 % risk after 5 years of withdrawl.
56

• Cautiously wean patients with persistent abnormal eeg / structural
lesion
• Patients with relatively treatable and self limitted derangements ( or
metabolic abnormalities ) = use for 7 days
• In acute brain insult – prophylactically, sometimes extend from one
month to 6 months
57

58
Thank You…..

Seizure new onset

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