Epilepsy: clinical presentation and management

Overview

Epilepsy:
Clinical presentation and management

Is it epilepsy?
Common attack disorders
How to differentiate between them

Markus Reuber
Professor of Clinical Neurology

Medical treatment of patients with epilepsy

Choosing appropriate treatment for focal or generalised epilepsy
Management strategies
What to do when medical treatments for epilepsy fail
Academic Neurology Unit
University of Sheffield,
Royal Hallamshire Hospital.

Epilepsy surgery
Vagus nerve stimulation
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Epilepsy: clinical presentation and management

Epilepsy: clinical presentation and management

Differential diagnosis

Differential diagnosis

Is it epilepsy?

Postural
syncope

Is it epilepsy?

Benign
Migraine
paroxysmal
Hypoglycaemia Positional vertigo

Dystonia

Epilepsy

T.I.A.

Parasomnia
Cardiogenic syncope

Blackouts
Problem with
blood circulation
(Syncope)

Cataplexy
Hyperventilation

Nonepileptic
seizure

Related to the
heart

Disturbance of
brain function

Low blood
pressure

Epileptic
seizures

Stress-related (nonepileptic seizures)

Unclassifiable
epilepsy

Idiopathic generalised
epilepsy

Focal
epilepsy

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Epilepsy: clinical presentation and management

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Epilepsy: clinical presentation and management

Definition

Characteristics

Epileptic Seizure

Epileptic Seizures
Duration: 30 120 seconds

Paroxysmal event in which changes of

behaviour, sensation or cognitive processes are
caused by excessive, hypersynchronous
neuronal discharges in the brain.

Positive ictal symptoms

Postictal symptoms
Stereotypical seizures / syndromal seizure types
May occur from sleep
May be associated with other brain dysfunction
Typical seizure phenomena: lateral tongue bite, dj vu etc.

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Epilepsy: clinical presentation and management

Epilepsy: clinical presentation and management

Definition

Characteristics

Syncope

Syncope
Situational

Paroxysmal event in which changes in

behaviour, sensation and cognitive processes
are caused by an insufficient blood or oxygen
supply to the brain.

Typically from sitting or standing

Rarely from sleep
Presyncopal symptoms
Duration 5-30 seconds
Recovery within 30 seconds
Cardiogenic syncope: less warning, history of heart disease

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Epilepsy: clinical presentation and management

Epilepsy: clinical presentation and management

Definition

Characteristics

Nonepileptic seizure

Nonepileptic seizures (NES)

Situational
Duration 1-20 minutes

Paroxysmal event in which changes in

behaviour, sensation and cognitive function
caused by mental processes associated with
psychosocial distress.

Dramatic motor phenomena or prolonged atonia

Eyes closed
Ictal crying and speaking
Surprisingly rapid or slow postictal recovery
History of psychiatric illness, other somatoform disorders
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Epilepsy: clinical presentation and management

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Epilepsy: clinical presentation and management

History taking: value of factual information

History taking: value of factual information

Epilepsy versus syncope: Factors suggestive of epilepsy

Epilepsy versus syncope: Factors suggestive of syncope

Hoefnagels 1991

Sheldon 2002

Sens

Spec

OR

Sens

Spec

OR

Tongue biting

0.41

0.94

7.3

0.45

0.97

16.5

Head turning

NR

NR

NR

0.43

0.97

13.5

Muscle pain

0.39

0.85

2.6

0.16

0.95

3.4

Loss of consciousness >5min

0.68

0.55

1.5

NR

NR

NR

Cyanosis

0.29

0.98

16.9

0.33

0.94

5.8

Postictal confusion

0.85

0.83

5.0

0.94

0.69

3.0

Colman N et al. Diagnostic value of history taking in reflex syncope. Clin Auton Res 2004:14 (suppl.1):I/37-44
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Hoefnagels 1991

Sheldon 2002

Sens

Spec

OR

Sens

Spec

OR

Prolonged upright position

NR

NR

NR

0.40

0.98

20.4

Sweating prior to LOC

0.36

0.98

18

0.35

0.94

5.9

Nausea

0.28

0.98

14

0.28

0.94

4.7

Presyncopal symptoms

NR

NR

NR

0.73

0.73

2.6

Pallor

0.81

0.66

2.8

NR

NR

NR

Colman N et al. Diagnostic value of history taking in reflex syncope. Clin Auton Res 2004:14 (suppl.1):I/37-44
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Epilepsy: clinical presentation and management

History taking: value of factual information

Epilepsy: clinical presentation and management

Common diagnostic mistakes

Epilepsy vs. NES

D. Smith et al., Q J Med 1999; 92: 15-23

Limitation

Feature in the history suggesting NES

Little differentiating value

Pelvic thrusting, no ictal injury, no seizures from

sleep, no incontinence or tongue biting.

Differentiate but not noticed /

described reliably

Long duration, closed eyes / mouth during tonicclonic movements, no cyanosis

Differentiate but not

commonly reported

Pre-ictal anxiety symptoms, ictal crying, ictal

weeping, vocalisation during tonic-clonic phase

Differentiate but require

expert observation

Unusually rapid or slow recovery, change in amplitude but not frequency of motor activity, reactivity

Depend on observations of a seizure witness

26.1% of patients referred to an epilepsy clinic for specialist

management of refractory seizures did not have epilepsy
Most commonly made mistakes:
- Incomplete history, lack of witness account
- Misinterpretation syncopal, myoclonic jerks
- Misinterpretation of EEG-changes
Consequences of misdiagnoses:
- 100% treated with anticonvulsants
- 39% unemployed
- 41% barred from driving

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Epilepsy: clinical presentation and management

Common diagnostic mistakes
M. Reuber et al., Neurology 2002;58:493-495
Diagnostic delay in patients with nonepileptic seizures
120

Mean delay:

100

Part 2

7,2 years

80

Medical treatment of patients with epilepsy

Manifestation
Diagnosis

60
40
20

69

>7
0

59

60
-

49

50
-

39

29

40
-

30
-

19

20
-

10
-

09

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Epilepsy: clinical presentation and management

Medical treatment of epilepsy

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Epilepsy: clinical presentation and management

Seizure classification and prevalence
How common are the different seizure syndromes?

Starting treatment for patients with epilepsy

Is it epilepsy?

Focal

Is treatment indicated?

Generalised
Unclassifiable

What type of epilepsy is it ?

Provoked / Acute

What is the most appropriate drug of first choice?

From: Loiseau et al. Epilepsia 1990; 31: 391-396
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Epilepsy: clinical presentation and management

Epilepsy: clinical presentation and management

Epilepsy syndromes

Focal epilepsy

Focal epilepsy

Hippocampal sclerosis (mesial temporal sclerosis)

Associated with focal brain abnormality, may start at any age

Seizure types:
- Partial seizures without impairment of consciousness.
(e.g.: Jacksonian seizures, Dj vu)

- Partial seizures with impairment of consciousness

(e.g.: Psychomotor seizures)
- Secondary generalised seizures
First line treatment: Carbamazepine or lamotrigine
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Epilepsy: clinical presentation and management

Epilepsy: clinical presentation and management

Focal epilepsy

Focal epilepsy

EEG during a right temporomesial seizure (1)

EEG during a right temporomesial seizure (2)

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Epilepsy: clinical presentation and management

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Epilepsy: clinical presentation and management

Focal epilepsy

Epilepsy syndromes

EEG during a right temporomesial seizure (3)

Idiopathic (primary) generalised epilepsy

No associated brain abnormality, manifestation usually <30 years
Seizure types:
- Absence seizures
(e.g.: childhood absence epilepsy, juvenile absence epilepsy)
- Myoclonic seizures
(e.g.: in juvenile myoclonic epilepsy)

- Primary generalised tonic clonic seizures

(e.g.: Grand mal on awakening)

First line treatment: Valproate or lamotrigine

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Epilepsy: clinical presentation and management

Epilepsy: clinical presentation and management

Generalised epilepsy

Medical treatment of epilepsy

Genetic (primary) generalised epilepsy

Focal seizures
Carbamazepine
Oxcarbazepine
Eslicarbazepine
Phenytoin
Vigabatrin
Gabapentin
Tiagabine
Pregabalin
Perampanel

Focal & generalised

Generalised seizures

Valproate
Lamotrigine
Topiramate
Levetiracetam
Zonisamide
Felbamate
Phenobarbitone
Primidone
Lacosamide
Retigabine?

Ethosuximide
(absence only)
Rufinamide

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Epilepsy: clinical presentation and management

Epilepsy: clinical presentation and management

Medical treatment of epilepsy

General principles

Using antiepileptic drugs

Using antiepileptic drugs

Monotherapy: increase to lowest possible effective dose

Monotherapy: increase to fully effective / maximum tolerated dose
Consider alternative monotherapy / combination therapy
Consider epilepsy surgery (vagal nerve stimulator)

Treatment scenario

% of patients seizure-free

All patients (N=525)

63%

First AED monotherapy

47%

Second / third AED monotherapy

14%

Combination therapy

3%

Consider reduction to monotherapy in very refractory epilepsy

From: Kwan P, Brodie JM, NEJM 2000, 342:314-319
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Epilepsy: clinical presentation and management

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Epilepsy: clinical presentation and management

Medical treatment of epilepsy

Medical treatment of epilepsy

Drawbacks of conventional AEDs

Side-effects and idiosyncratic reactions of new AEDs

Drawback

Drugs

Drug

Side-effects

CBZ, PB, PRM, PHT, (VPA)

Lamotrigine (LTG)

Allergic-toxic reactions

Significant longterm side-effects

VPA, PHT, CBZ, PB, PRM

Vigabatrin (VGB)

Irreversible, concentric visual field defect,

weight gain

High teratogenic potential

VPA

Gabapentin (GBP), Pregabalin (PGB)

Weight gain

Hepatic enzyme induction / (inhibition)

CBZ, PHT, PB, PRM / (VPA)

Topiramate (TPM)

Non-linear pharmacokinetics

CBZ, PHT, VPA

Cognitive dysfunction, renal stones, acute

ocular syndrome, weight loss, paraesthesia

Oxcarbazepine (OXC)

Hyponatraemia

Common cause of drug interaction

CBZ, VPA, PHT, PB, PRM

Levetiracetam (LEV)

Behavioural change

Significant cognitive side-effects

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Epilepsy: clinical presentation and management

What to do if medical treatments for epilepsy fail
Available procedures for the treatment of refractory epilepsy
Curative intent

Part 3

Palliative intent

Resective Sx Hemispherectomy

What to do if medical treatments for epilepsy fail

Tractotomy

Electrostimulation

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Epilepsy: clinical presentation and management

Epilepsy: clinical presentation and management

What to do if medical treatments for epilepsy fail

What to do if medical treatments for epilepsy fail

Basic conditions for epilepsy surgery with curative intent

Outcomes of epilepsy surgery

Tonini et al. 1997, meta-analysis, focal epilepsy, 1987-1996:
- Engel Class I:
59%
- Engel Class II:
15%
- Engel Class III:
12%
- Engel Class IV:
12%
- Frontal lobe (EC I):
40%

Movement

Memory

Vision

Wiebe et al. 2000, randomised, ant. temporal lobectomy vs. AED,

complete seizure remission at one year:
- Epilepsy surgery:
38% (ITT analysis, otherwise 64%)
- AEDs:
8%
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Epilepsy: clinical presentation and management

Epilepsy: clinical presentation and management

What to do if medical treatments for epilepsy fail

Summary

Vagal nerve stimulation

Diagnosis

Medical treatment

Misdiagnosis is
70% of patients
common
should become
Epilepsy is
seizure-free with
overdiagnosed
AEDs
Patient and witness New AEDs are no
history are
more effective
essential
than conventional
Consider syncope
AEDs but have
and NES
fewer side-effects

Stimulates 30 sec every 5 minutes

Evidence:
- 28% mean seizure reduction
- 1/3 of patients >50% reduction
- Very few patients seizure-free

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Other treatments
Epilepsy surgery is
very effective if
feasible
Vagus nerve
stimulation
is a palliative
treatment option for
refractory epilepsy

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The End

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