By\ Doha Rasheedy Aly

Epilepsy:
 is a chronic condition defined by
repeated and intermittent seizures,
caused by abnormal electrical activity
within the brain.
 Of all the nervous system disorders,
epilepsy is the largest cause of
hospitalizations
 What is an epileptic seizure?

 A transient occurrence of signs and/or

symptoms due to abnormal excessive
or synchronous neuronal activity in
the brain.
 Commonly generated in cortex and
hippocampus, may also be
subcortical
Status epilepticus:
 This is defined as a condition in which
epileptic seizures continue, or are
repeated without recovery, for a period
of 30 minutes or more.
 Idiopathic, symptomatic and
cryptogenic epilepsy
 Epilepsy can have many causes. Where
the cause is clearly identified, the
epilepsy is categorized as
‘symptomatic’(i.e. of known cause).
 Where no cause is known, the epilepsy
is known as ‘cryptogenic’ (i.e. hidden
cause).
 Where the epilepsy is part of the genetic
syndrome of ‘idiopathic generalized
epilepsy’ it is known as idiopathic.
Provoked seizures (acute symptomatic seizures)
 have an obvious and immediate preceding cause
(for instance an acute systemic or metabolic
disturbance or exposure to toxins or drugs), or
which are the direct result of recent acute cerebral
damage (for instance stroke, trauma, infection).
 often do not recur when the cause is removed.
 The use of the term to include seizures after acute
cerebral damage, however, is rather
unsatisfactory as the damage is not reversible and
the propensity for seizure recurrence is higher
 Provoked seizures: causes
1.the most common cause of provoked seizures in
elderly people is acute stroke.
 Systemic disorders precipitating acute seizures can
involve metabolic or electrolyte disturbances,
including:
○ hypoglycaemia
○ hyperglycaemia,
○ uraemia,
○ Hyponatraemia
○ hypocalcaemia,
○ Hypothyroidism
○ pneumonia,
○ urosepsis,
○ hepatic failure.

 Seizures secondary to acute central nervous system

infections occur more commonly in developing
countries than in developed countries.
Provoked seizures: causes- continued

 Drugs: including :
○ Antipsychotics
○ Antidepressants
○ Antibiotics
○ Theophylline
○ Levodopa
○ Thiazide diuretics,
○ The herbal remedy ginkgo biloba.
 Alcohol withdrawal seizures are not
uncommon in this population.
Stroke and epilepsy
 Approximately 7% of ischaemic and15% of
haemorrhagic cortical strokes are complicated
by acute or early seizures (within 2 weeks of
stroke onset),and approximately one-third of
these patients develop late epilepsy.
Predictors of seizures with ischemic
stroke include:
 severity (initial and persistent)
 large size
 embolic cause
 involvement of the cortex, hippocampus or
multiple brain areas.
 Seizures may be less likely to occur with
occlusions related to cervical dissection than
with atherosclerotic occlusions
Pathophysiology of early
seizures and late seizures
 Early seizures may be related to acute
changes such as metabolic derangements
(increased penumbral sodium and intracellular
calcium), excessive glutamate, downregulation
of gamma aminobutyric acid (GABA)ergic
inhibition, hypoxia, hypoperfusion, and
irritation by blood products.
 Late seizures likely result from chronic
abnormalities such as scarring, changes in
neuronal excitability, and hemosiderin
deposition.
 First unprovoked seizure and
epilepsy
 Older people who present with a first unprovoked seizure are
more likely to develop seizure recurrence than are younger
adults. Epilepsy is usually diagnosed after the occurrence of two
or more unprovoked seizures.
 Previous stroke is the most common underlying problem,
accounting for 30-40% of all cases of epilepsy.
 Asymptomatic cerebral infarction can also lead to epilepsy, and,
paradoxically, seizures may be a marker of increased risk for
subsequent stroke. Alzheimer's disease and other dementias are
associated with a fivefold to 10-fold increase in the risk of
epilepsy, which usually develops in the advanced stage.
 Brain tumors and head trauma are relatively uncommon causes
of epilepsy in elderly people..
EPILEPSY IN THE ELDERLY
epidemiology:
 Epileptic seizures are the third most
frequently identified neurological condition
identified in the elderly, with only
cerebrovascular disease and dementias
being more common.

 When plotted against age, the incidence of

epilepsy has a distinctly U-shaped
distribution, with children under 5 years
and people over 60 years of age having an
elevated risk of epilepsy.
 in the older age group the incidence of partial
(focal) onset epilepsy outstrips that of
generalized epilepsy.

 Status epilepticus, which may be convulsive or

non-convulsive, accounts for approximately 6%
of all seizures in the aged, which is twice that
found in the general population.
 Etiology:
 stroke : the most common etiology in elderly
patients

 degenerative disorders such as Alzheimer’s
disease, approximately16% of all patients with
Alzheimer’s disease will go on to develop
seizures
 head trauma, tumour
 toxic/metabolic factors and drug induced
seizures
Conditions that provoke seizures
 Metabolic abnormalities
 Hypoglycemia
 Hypo and hypernatremia
 Hypo and hypercalcemia
 Hypomagnesemia
 Uremic encephalopathy
 Hepatic encephalopathy
 Systemic infection
 Sleep deprivation
 Drugs
 Intoxication with stimulants
○ Amphetamines
○ Cocaine
 Withdrawal from sedatives
○ Alcohol
○ BZD
○ Barbiturate

 An unprovoked seizure has no clear

underlying cause, and increases the risk
of further seizures
 Drug induced seizures
 Theophylline is a potent convulsant which can
result in seizures or status epilepticus, possibly due
to the antiadenosine action.
 β-blockers and other antiarrhythmic agents have
been reported to precipitate seizures, particularly in
overdose.
 Cimetidine, levodopa, insulin, thiazide diuretics,
lidocaine, salicylates, chemotherapeutic agents, L-
asparaginase and baclofen have been reported to
cause seizures.
 The non-steroidal analgesics also predispose to
seizures (for example NSAIDs, tramadol pethidine).
Presentation
 the presentation of epilepsy in old age is
often less specific.
 Up to 70% of seizures are of focal onset,
with or without secondary generalization.
 Complex partial (focal) seizures may present
with atypical features such as memory
lapses, episodes of confusion, periods of
inattention, or apparent syncope.
Differential diagnoses of seizures
in elderly people
 Neurological
• Transient ischemic attack
• Transient global amnesia
• Migraine
• Narcolepsy
• Restless legs syndrome
 Cardiovascular
• Vasovagal syncope
• Orthostatic hypotension
• Cardiac arrhythmias
• Structural heart disease
• Carotid sinus syndrome
 Endocrine/metabolic
• Hypoglycaemia
• Hyponatraemia
• Hypokalaemia
 Sleep disorders
• Obstructive sleep apnoea
• Hypnic jerks
• Rapid eye movement sleep
disorders
 Psychological
 • Non-epileptic
psychogenic seizures
 Characters of epilepsy in elderly
 Focal seizures are more common than generalized seizures in the
elderly.
 An aura is less common and, if present, tends to be non-specific
(such as dizziness).
 Automatisms are usually not present and seizures may manifest only
with a blank stare and impairment of consciousness.
 Postictal confusion tends to be prolonged in the elderly, lasting for
hours and sometimes days to weeks, and may lead to an erroneous
diagnosis of dementia.
 secondarily generalized tonic-clonic seizures were found to occur in
only 26% of elderly patients, as opposed to 65% of younger adults.
 anatomical origin of seizures, which is more likely to be mesial
temporal in younger patients and extratemporal, especially frontal, in
the elderly.
 Idiopathic generalized epilepsy beginning in the elderly is
much less common.
 Work up new onset seizure
 Routine investigations should include:
○ full blood count
○ renal function testing
○ serum electrolytes
○ and random blood glucose.
○ An electrocardiogram
○ a chest radiograph
○ Brain imaging: Magnetic resonance imaging is more sensitive than
computed tomography in detecting relevant anatomical abnormalities
 The need for more specialized investigations, including ambulatory
prolonged electrocardiography and tilt table testing, should be guided by
the clinical scenario.
 When the diagnosis is in doubt, the patient can be referred to a specialist
centre for videoelectroencephalographic monitoring.
Classification of epilepsy:
DIAGNOSIS OF EPILEPSY IN
ELDERLY IS DIFFICULT:
 Due to:
 great imitators :syncope, episodic vertigo,
hypoglycaemia, metabolic disorders, transient
ischemic attacks, non-specific episodes of
dizziness, confusional states, transient global
amnesia or psychiatric illness.

 On the other hand, focal seizures may remain

ignored and be a cause of underdiagnosis of
epilepsy. Symptoms as confusional states,
hallucinations or automatisms are misleading and
frequently considered as manifestations of
neurodegenerative or psychiatric disorders
 There is a different distribution of seizure
types and epilepsy syndromes in the elderly
compared to younger patients.

 1- Primary generalised epilepsy rarely occur

 2- The majority of seizures are partial, either
simple, complex or secondarily generalised.
 3-Status epilepticus, both convulsive and
non-convulsive, is relatively common in the
aged,
 the diagnosis becomes challenging
because the symptomatology of simple and
complex partial seizures can be subtle.
elderly patients do not exhibit automatisms;
consequently, a disturbance of
consciousness with a blank stare or brief
gaps in conversation or periods of
confusion may be the only manifestation of
a complex partial seizure.
 One of the most striking differences
between older and younger adults is the
length of the postictal confusional state,
which may last for hours, days, or even l to
2 weeks in older patients compared with
minutes in younger adults.
 Electroencephalograms (EEGs) often are
nonspecific, showing focal or generalized
slowing in this population, or are even
normal (31%).

 Interictal epileptiform activity is present in

only 26% to 38% of initial EEGs of patients
ultimately diagnosed with seizures

 Few seizures after stroke (only 10% to

20%) and few cerebral tumors (10% to
20%) have interictal epileptiform activity on
EEG
Common differential diagnoses of seizures

 Neurological
 TIA
 Migraine
 Cardiac
 Vasovagal syncope
 Arrhythmias
 Metabolic
 Hypoglycemia
 Psychiatric
 Non-epileptic seizures
Diagnostic evaluation

 A thorough history, examination,

neuroimaging, and EEG are indicated in
the diagnostic evaluation. If collectively
the results are inconclusive, then
prolonged inpatient EEG video
monitoring is recommended.
History:
 from the patient and observers
 Seizures are, paroxysmal, unpredictable, and
usually stereotyped from patient to patient.
 Focal paroxysmal transient deficits in
language, memory,motor, or sensory testing
can occur not only with TIAs and such
syndromes as transient global amnesia but
also as the first manifestation of partial
seizures (aura) or more commonly after a
seizure (postictal Todd paralysis).
 By history, the description can help with seizure
recognition and localizationof the potential
focus, which may be further supported by
examination andimaging findings.
 Before the event
 Provoking factors
 Preceding symptoms (aura)
 Duration of symptoms
 During the event
 Motor symptoms
 Level of consciousness
 Injury
 Incontinence
 Duration
 After the event
 Confusion
 Focal neurologic signs
 Duration
Physical examination
 General examination
 Injury or Signs of infection
 Neurological examination
 Assess mental status
○ Post-ictal state
 Look for focality, may be indicative of an
underlying lesion or a Todd’s paralysis
 Cardiological examination (to exclude)
 arrhythmia or orthostatic hypotension
 A tilt table test can be helpful diagnostically in this population,
particularly if it reproduces exactly the reported stereotyped
symptoms
Neuroimaging:
 Neuroimaging is essential in the evaluation,
particularly in older patients whose seizures
are often attributable to structural
abnormalities.
 Magnetic resonance imaging (MRI) is the
imaging of choice in patients with epilepsy
and is particularly useful in those:
 who have suggestions of a focal seizure onset
from history, examination or EEG.
 in whom seizures continue in spite of first line
medication
 Computed tomography (CT) scan has a
role in the urgent assessment of seizures or
when MRI is contraindicated
 EEG
 Routine recording is 30 minutes
 Looking for:
 Background rhythm. May be generally slow in
dementia. Focally slow with tumor or stroke
 “Epileptogenic” features, like sharp waves or
spikes
 May be normal or non-specific in ~50% of seizure patients,
Rare to capture a seizure, normal EEG doesn’t exclude
epilepsy
 interictal epileptiform activities were recorded less often (26-
37%)
 specific indication for EEG recording in elderly patients, even
in emergency conditions, is the suspicion of non convulsive
status epilepticus when the patient is confused without known
aetiology as metabolic disorder.
Inpatient electroencephalogram
video monitoring
 Long-term video or ambulatory EEG
may be used in the assessment of
individuals who present diagnostic
difficulties after clinical assessment and
standard EEG
Other required investigations
 Routine blood studies are indicated to
identify common metabolic causes of
seizure such as abnormalities in
electrolytes, glucose, calcium, magnesium,
hepatic and renal diseases.
 Screening for toxins is sometimes done.
 Lumbar puncture is necessary when
meningitis or encephalitis is suspected
 Electrocardiogram (ECG) should be
performed in the assessment of all elderly
patients with altered consciousness, when
cardiac arrhythmias can simulate epilepsy
When to start treatment
 After one unprovoked seizure?
 Recurrence in elderly: 34% in 5 years
 Higher risk of recurrence if:
○ Underlying structural brain lesion
○ Abnormal EEG
○ in patients with Todd’s paralysis
 After more than one?
 The risk of seizure recurrence after 2
unprovoked seizures is 73%.Antiepileptic
drugs therefore should be offered to the
patient after explaining the risks and benefits
and after assessing his/her preferences
Withdrawal of treatment
 Whether treatment can be safely
withdrawn after a period of seizure
freedom has not been determined, so
most older patients will remain on
antiepileptic drugs for life.
Classification of Anticonvulsants
 Classical  Newer
 Lamotrigine
 Phenytoin
 Felbamate
 Phenobarbital  Topiramate
 Primidone  Gabapentin
 Carbamazepine  Tiagabine
 Vigabatrin
 Ethosuximide
 Oxycarbazepine
 Valproic Acid  Levetiracetam
 Trimethadione  Fosphenytoin
  Others
Action on Ion Enhance GABA Inhibit EAA
Channels Transmission Transmission

Na+: Benzodiazepines Felbamate

Phenytoin, (diazepam, Topiramate
Carbamazepine, clonazepam)
Lamotrigine Barbiturates
Topiramate (phenobarbital)
Valproic acid Valproic acid
Ca++: Gabapentin
Ethosuximide Vigabatrin
Valproic acid Topiramate
Felbamate
Special considerations in the elderly

 Decreasing renal and hepatic function

 Decreased ratio of muscle to fat
 Decreased binding of drugs to albumin
 Higher susceptibility to toxicity
 Polypharmacy
Antiepileptic Choice:
 Matches epilepsy seizure type:
 Partial seizure, 2ry generalization:
carbamazepine, valproate
,lamotrigine, oxycarbazepine

 generalized seizure
valproate ,lamotrigine

 Uncertain type:
valproate ,lamotrigine
 Consider side effects profile, cost of the drug
 Start with low dose of 1st line antiepileptic drugs (AEDs)
is often necessary due to age-related changes in renal
and hepatic function (monotherapy)

 Increase dosage gradually till least effective dose to

minimize side effects.

 Monitor drug response by:

 Reduction in seizure frequency

 Reduction in seizure severity

 Onset of side effects

 Not by drug therapeutic level

 When initiating therapy, increase doses
slowly, until seizure control is achieved
or side effects occur. If seizures are
controlled, obtain a serum concentration
at that time. This will identify the patient’s
‘therapeutic optimal level’.
 Routine checking of antiepileptic drug
levels without a clear clinical indication is
not required, and is not cost-effective
Pt not controlled:
Change to another drug (1st line therapy) with tapering
the 1st drug gradually after 2nd drug become
therapeutic. (add on therapy)
 In patients resistant to monotherapy:
1- review diagnosis of epilepsy, adherence to
medication.
2-Combination of 2 of 1st line drugs the first is the drug
produced well tolerated improvement in seizures
control but fail to produce seizure freedom at
maximal dose
3- the 2 drugs better to have different mechanisms of
action, but both matches epilepsy type. Maximal 3
drugs.
Monitor antiepileptic drug
 Antiepileptic drug levels may help clinical
management under the following clinical
indications:
 (1) Baseline therapeutic optimal level ?!
 (2)assessment of compliance to drug
treatment for patients with refractory
epilepsy compared to
 (3)assessment of symptoms due to
possible antiepileptic drug toxicity
 (4) titration of phenytoin dose.
Serum therapeutic level
Carbamazepine (Tegretol) 4 - 12
Ethosuximide Zarontin 40 - 100
Phenobarbital 20 - 40
Phenytoin Epanutin 5 - 25
Fosphenytoin
(Cerebyx)
Valproic acid Depakene) 50 -
100
Primidone 5 - 12
Gabapentin Neurontin) 4 -16
Lamotrigine Lamictal 2 - 20
Levetiracetam Keppra 20 - 60
Oxcarbazepine Trileptal 5 - 50 (MHD
Pregabalin Lyrica 5 - 10
Tiagabine Gabitril 5 - 70
Topiramate Topamax 2 - 25
Zonisamide Zonegran 10 -
40
Felbamate Felbatol 40 - 100
Monitor side effects
 According to antiepileptic drug :
 Types of adverse effect
 Idiosyncracy
 Dose dependent: mostly appear within
6 months of treatment (not followed after
6 m)
Decision to Stop Treatment
 If the patient has been seizure free for at
least three years(3-5), particularly if
epileptiform activity has disappeared from
the EEG risk factors for recurrence include
slowing or spikes (maximum risk with both
present) on EEG (not mandatory), the
possibility of ceasing antiepileptic drug
therapy could be considered.
 If the patient has had multiple seizures prior
to commencing treatment, or the epilepsy
has been difficult to control, a more
conservative approach is recommended,
and medication should be continued longer
term.
 If medication is to be withdrawn, this should
be done gradually over (6 weeks ) several
months and even more slowly for
barbiturates.
 Recurrence of seizures with medication
withdrawal, prior medication should be
reinstituted at the previously effective
levels.
Phenytoin gingival hypertophy
withdrowal
Other treatment options:
 Vagus nerve stimulation is indicated for
adjunctive therapy and has been shown
to reduce frequency of seizures in
patients refractory to antiepileptic
medication who are not suitable for
epilepsy surgery. This includes adults
whose epileptic disorder is dominated by
partial seizures (with or without
secondary generalisation) or
generalised seizures
Resective Surgery for Epilepsy in
Older Adults
 In younger adults, temporal lobectomy, the most
common surgical procedure for epilepsy, is readily
performed in most settings and its efficacy and
safety have been well documented.
 the risk of complications is somewhat higher
compared with that in a younger control group. The
finding of lower post-operative neuropsychological
performance is a cause for concern. The debate
will probably continue as to whether epilepsy
surgery should be performed in older adults.
Clearly, more care must be taken with epilepsy
surgery evaluations before any decision is made to
proceed with a resective procedure. Nevertheless,
some individuals can benefit from surgery.
Status epilepticus
 Status epilepticus is defined as a condition
in which epileptic activity persists for 30
minutes or more. The seizures can take the
form of prolonged seizures or repetitive
attacks without recovery in between.
 Non conulsive status epilepticus: NCSE
 The diagnosis of NCSE is critically
dependent on EEG. In patients with a
previous diagnosis of epilepsy, any
prolonged change in personality, prolonged
postictal confusion (greater than 30 min) or
recent-onset psychosis should be
investigated with EEG as these can all be
presentations of NCSE
Status epilepticus types
Causes of Status epilepticus
 Anticonvulsant non compliance
 Infection
 Pre-existing epilepsy
 Metabolic
 Acute stroke
 Tumor related
 Alcohol or other drug withdrawal
 Drug intoxication
 Acute hypoxic–ischemic encephalopathy
 Acute trauma
 Miscellaneous or undetermined
 Treatment of Status Epilepticus in Older People

 Status epilepticus is treated in a manner

similar to younger patients.
 Initial management:
 Assessment and control of airways and ventilation
 Arterial blood gas monitoring
 Electrocardiogram (ECG)
 Blood pressure monitoring
 Intravenous (i.v.) glucose and thiamine
 Emergency measurement of antiepileptic drug levels
 Emergency measurement of electrolytes and magnesium
 Full haematological screen
 Measurement of hepatic and renal function
 Phenobarbital, phenytoin, and carbamazepine can produce idiosyncratic reactions, in
particular skin rashes, and complex drug-drug interactions, as they are all substrates
for and inducers of hepatic monooxygenase enzymes. They can interact with a wide
range of lipid soluble drugs commonly used in elderly people, including warfarin,
cardiac antiarrhythmics, theophylline, corticosteroids, antidepressants, cytotoxics,
macrolide antibiotics, and St John's wort.17
 Enzyme induction also accelerates the catabolism of vitamin D, leading to decreased
calcium absorption, secondary hyperparathyroidism, and increased bone loss.18 Some
authorities recommend calcium and vitamin D supplements and regular bone density
measurements for elderly patients at particular risk of osteoporosis—for example,
because of prolonged treatment, multiple drugs, or non-ambulatory lifestyle.w26
 Sodium valproate has a broad spectrum of activity and is the drug of choice for the
unusual idiopathic generalised epilepsy syndrome presenting late in life. It may have a
slightly better cognitive and behavioural profile than the other established antiepileptic
drugs.16 In addition, valproate does not induce hepatic drug metabolising enzymes. It
can reduce bone mineral density, however, possibly by interfering with osteoblastic
function.w27 Valproate can also produce dose dependent tremor and reversible
parkinsonism.w28
 For adult patients with severe traumatic brain
injury (TBI) (typically with prolonged loss of
consciousness or amnesia, intracranial
hematoma or brain contusion on computed
tomography [CT] scan, and/or depressed skull
fracture):
 Prophylactic treatment with phenytoin,
beginning with an intravenous (IV) loading
dose, should be initiated as soon as possible
after injury to decrease the risk of post-
traumatic seizures occurring within the first 7
days (Level A).
 Prophylactic treatment with phenytoin,
carbamazepine, or valproate should not
routinely be used beyond the first 7 days after
injury to decrease the risk of post-traumatic
seizures occurring beyond that time (Level B).
 The 30-day risk of seizures after ICH is about 8%.
Seizures most commonly occur at the onset of
hemorrhage and may even be the presenting symptom.
Lobar location is an independent predictor of early
seizures.

 Although, no randomised trial has addressed the

efficacy of prophylactic antiepileptic in ICH patients, the
Stroke Council of the American Heart Association
suggest prophylactic antiepileptic treatment may be
considered for 1 month in patients with intracerebral
hemorrhage and discontinued if no seizures are noted.

 Acute management of seizures entail administering

intravenous lorazepam (0.05–0.10 mg/kg) followed by an
intravenous loading dose of phenytoin or fosphenytoin
(15–20 mg/kg), valproic acid (15–45 mg/kg), or
phenobarbital (15–20 mg/kg).
 Patients who develop recurrent early or late
postischemic stroke seizures generally require
pharmacological treatment.

 An observational hospital-based study and a

prospective cohort study showed that 54% and
67% of patients with cerebral infarction and
epilepsy were seizure-free for at least 1 year
with the majority of patients being treated with a
single drug
 phenytoin benzodiazepines lamotrigine,
topiramate, levetiracetam and zonisamide have
neuroprotective properties and might, therefore,
have beneficial effects when used to treat
seizures in the setting of hyperacute stroke
 However, there remain no clinical data that
administration of anticonvulsant drugs after
stroke, or other acute brain injuries, prevents
the later development of epilepsy

 Based on experimental studies, there is some

concern that the use of phenytoin,
phenobarbital, and benzodiazepines may
impair poststroke recovery
 The relationship between stroke and
seizures may be bidirectional in the
elderly, as some studies have shown
that the risk of stroke is increased by
nearly three-fold in patients with late-
onset seizures.
 It is therefore advisable to investigate
patients with late-onset seizures for
stroke risk factors and treat them
appropriately.
 In patients with newly diagnosed brain tumors,
anticonvulsant medications are not effective in
preventing first seizures. Because of their lack
of efficacy and their potential side effects,
prophylactic anticonvulsants should not be
used routinely in patients with newly
diagnosed brain tumors

 in patients with brain tumors who have not had

a seizure, tapering and discontinuing
anticonvulsants after the first postoperative
week is appropriate, particularly in those
patients who are medically stable and who are
experiencing anticonvulsant-related side
effects