A review of epilepsy in the elderly, the etiopathogenesis, clinical challenges, diagnosis, use of antiseizure drugs and outcomes. Also the various special considerations in managing elderly patients with epilepsy.

1. Epilepsy in the Elderly
Dr Pramod Krishnan
Consultant Neurologist and Epileptologist
Manipal Institute of Neurological Disorders
Manipal Hospital, Bangalore

2. Introduction
• Seizures and epilepsy are 3rd most common neurological disorder
affecting older adults, after stroke and dementia.
EPILEPSY IS NOT A DISEASE LIMITED TO YOUNG PEOPLE

3. Bacellar A et al. Open Neurology J 2018: 12; 1-11.
Elderly patients admitted with neurological disorders

4. Challenging aspects in the Elderly
• Age related physiological changes.
• Altered pharmacokinetics.
• Altered pharmacodynamics.
• Comorbidities and comedications.
• Safety issues, falls, cognitive aspects.
• Bone health.
• Seizures may be symptomatic of other systemic illness.

5. Epilepsy in the elderly population requires coordination with
primary care physicians as well as specialty care physicians.

6. The incidence of new-
onset epileptic seizures
as a function of age
Olafsson E, et al. Lancet Neurol 2005; 4: 627–34

7. Incidence
• Incidence of seizures (symptomatic, unprovoked) and epilepsy are
highest in people >65 years of age.
• Incidence is highest in those >75 years of age (5 times that of
young adults).
• Overall incidence in elderly is 2.4/1000 per year.
• Approximately 24% of new-onset epilepsy occurs after age 60.
Faught E, et al. Neurology. 2012;78:448-453.

8. Incidence of epilepsy
(per 100,000/years) in
various countries,
overall and in selected
age groups in the
elderly.
Giussani G, et al. Neuroepidemiology 2018;51:216–223

9. Prevalence
• Prevalence of unprovoked seizures is 1% in those >60 years of age.
• In those > 75 years of age it is 1.2-1.5% (twice that of young
people).
• In a study of 1 million US citizens aged >65 years, 1.8% had
epilepsy.
• Overall prevalence of epilepsy in the elderly is 10.8/ 1000.
Sander JW, et al. Lancet. 1990;336:1267-1271.

10. Prevalence of
epilepsy (per 1,000)
in various countries,
overall and in
selected age groups
in the elderly.
Giussani G, et al. Neuroepidemiology 2018;51:216–223

11. ETIOLOGY

12. Hauser WA, et al. Epilepsia 1993; 34: 453–68.

13. Etiology of Epilepsy is different
in elderly compared to young
patients, with a predominance
of acquired causes.
Fujimoto A, et al. Neuropsychiatric Disease and Treatment 2018:14 2879–2887

14. Etiological prevalence of epilepsy in hospitalised
patients aged 60 years or more in a tertiary care
centre in Brazil.
Nascimento M, et al. Arq Neuropsiquiatr 2015;73(2):83-89

15. Etiological prevalence of epilepsy in the subgroup
of hospitalised patients aged at least 75 years old
(median age) in a tertiary care centre in Brazil.
Nascimento M, et al. Arq Neuropsiquiatr 2015;73(2):83-89

16. Cerebrovascular disease
• It is the leading identified
cause of new-onset epilepsy in
the elderly.
• It accounts for up to half of
new cases of epilepsy.
• Patients have a 11.5%
probability of seizures within 5
years of stroke onset.

17. Bi-directional interface between cerebrovascular disease (CVD) and epilepsy
Gibson LM, et al. Journal of Cerebral Blood Flow & Metabolism (2014), 564 – 570

18. Possible interrelationships in the pathophysiology of epileptogenesis associated with
occult cerebrovascular disease (CVD).
Gibson LM, et al. Journal of Cerebral Blood Flow & Metabolism (2014), 564 – 570

19. Dementia and Epilepsy
• High seizure frequency increase risk of cognitive decline.
• Upregulation of APP, increase in senile plaques, premature
accumulation of corpora amylacea.
• Presence of apoE-e4 allele in TLE accelerates cognitive decline.
• Epilepsy patients aged 50-75 yrs have increased risk of dementia.
• Upto 10-20% of people with Alzhiemers disease have epilepsy. The
risk of epilepsy is 6 fold.
• In non-Alzheimers dementia: the risk is 8 fold.

20. Etiology
• Brain tumors (primary, metastatic): 10% to 30% of new cases.
• Traumatic brain injury and extraparenchymal hemorrhages (eg,
SDH, SAH), a frequent sequelae of falls, are also seen.
• Paraneoplastic and autoimmune causes of epilepsy.
• Psychiatric illness (BPAD, depression, schizophrenia, substance
abuse) have a higher risk of seizures.

21. DIAGNOSIS
“The most powerful diagnostic tool is an accurate history
of the onset, evolution of and recovery from the episode”.

22. Diagnosis
Veteran Affairs Cooperative Study of seizures in >60 year olds.
• Epilepsy was a diagnostic consideration in only 73% of patients,
all of whom had epilepsy.
• Only 37% were correctly diagnosed on initial evaluation.
• Mean time to correct diagnosis was 2.3 years.
Rowan AJ, et al. Neurology 2005; 64: 1868-1873
“The greatest challenge to a correct diagnosis is the
differentiation of seizures from syncope”.

23. Feature Syncope Seizure
Pre-ictal
Trigger (position, emotion, Valsalva) Common Rare
Sweating, nausea Common Rare
Aura Rare Common
Ictal
Unilateral symptoms Rare Common
Pallor Common Rare
Cyanosis Rare Common
Duration of LOC <30 sec >60 sec
Movements Few clonic, myoclonic jerks <15sec. GTCS, focal seizures, myoclonic.
Automatism Rare In CPS.
Tongue bite Rare, may be anterior tongue injury Lateral. Occasional.
Frothing Rare Common
Ictal EEG Non-specific slowing Ictal EEG pattern
Post-ictal
Confusion Rare. If present, it is brief (<30 sec). Common. Several minutes
Diffuse myalgia Rare, brief, upper body Hours to days.
CK elevation Rare. Common (after 12-24 hrs)
Inter-ictal EEG Normal Epileptiform discharges.

24. Common Diffferential
diagnosis.
Brodie MJ, et al. Lancet Neurol 2009; 8:1019–1130

25. Clinical presentation
• 70% of seizures are partial onset.
• However, even apparently generalised seizures in elderly should be
considered as partial onset unless proven otherwise.
• In a small VEEG study, 75% of seizures were of temporal origin.

26. Feature Young patients Elderly
Onset Focal, generalised Usually focal.
Location Temporal is relatively
common
Extratemporal is more common
Aura More common Less common
Ictus Focal onset, generalised Can be subtle, like memory lapses, altered
mental state, confusion.
Post-ictal state Less prolonged Prolonged confusion, drowsiness likely,
especially in those with pre-existing
cerebral dysfunction.
Etiology Acquired, genetic Usually acquired
Subclinical seizures Less common More common, especially in dementia pts
GCSE, NCSE Less common More common, especially NCSE
How are seizures in the elderly different from those in the young?

27. 1. EEG, especially
longer recordings
2. VEEG
Cardiac evaluation:
1. ECG
2. Holter, ELR
3. Tilt table testing
4. 2D ECHO
PSG
Blood investigations:
1. CBC
2. Na, K, Cl, Ca, Mg.
3. Renal parameters
4. LFT, Ammonia
1. MRI brain
2. Intracranial and
neck vessel
angiography
3. PET CT/MRI brain
1. LP CSF
2. Autoimmune
encephalitis panel.
3. Paraneoplastic
antibody panel.
4. Vasculitic and
CTD work up
New onset seizures in Elderly

28. TREATMENT

29. Risk of recurrence
• In all patients with new onset seizure, risk of recurrence over 2
years is 38%.
• Factors that increase recurrence risk:
1. IEDs on EEG
2. Epileptogenic lesion on MRI
3. Underlying identified cause
4. Seizures in sleep.
• If a cause is identified, risk of recurrence is double that of
cryptogenic first seizure.

30. Treatment of
Seizures/ Epilepsy
Acute
symptomatic
seizures
Unprovoked single
seizures
1. >1 Unprovoked seizure
2. Single Unprovoked
seizure with:
IEDs on EEG and /or
Epileptogenic lesion on
MRI
• Correct
underlying
cause.
• Short duration
of AEDs may be
required.
Normal EEG,
MRI
Start AED
AED therapy is
preferable
Status epilepticus
Yes
No
Levetiracetam
Sodium Valproate
Levetiracetam
Lamotrigine
Gabapentin
Sodium Valproate
Eslicarbazepine
Oxcarbazepine

31. Challenges in
therapy
Cognitive and
behavioural
issues
Hypo-
albuminemia
Bone health
Poor gastric
absorption
Reduced
renal
clearance
Reduced liver
mass and
blood flow
Presence of
Comorbid
illness
Co-
medications

32. Drug-Drug interactions
Phenobarbitone
Phenytoin
Sodium Valproate
Carbamazepine
Oxcarbazepine
Eslicarbazepine (mild)
Topiramate (high doses)
Dose adjustment in
renal disease
Levetiracetam
Lacosamide
Topiramate
Zonisamide
Gabapentin
Pregabalin
Cognitive side effects
Benzodiazepines
Phenobarbitone
Sodium Valproate
Carbamazepine
Oxcarbazepine
Topiramate
Steven Johnson
Lamotrigine
Phenytoin
Carbamazepine
Oxcarbazepine
Eslicarbazepine
AED Adverse effects
Sodium Valproate Hepatotoxicity, hyperammonemic encephalopathy, platelet
dysfunction, pancreatitis, parkinsonism.
Phenobarbital Dupuytrens contracture
Phenytoin Gingival hyperplasia, cerebellar atrophy, peripheral
neuropathy, zero order kinetics.
Topiramate Nephrolithiasis, Secondary angle closure glaucoma
Zonisamide
CBZ, OXC,
Eslicarbazepine
Hyponatremia, aplastic anemia. Least with Eslicarbazepine.

33. 12 month retention rate in older adults with epilepsy. Arif H, et al. Arch Neurol. 2010;67(4):408-415

34. Comorbidity Beneficial AED Harmful AED
Osteoporosis - Phenobarbitone, Phenytoin
Obesity Topiramate, Zonisamide Valproate, Gabapentin, Pregabalin
Depression Lamotrigine Levetiracetam, Phenobarbitone
Anxiety Gabapentin, Pregabalin Levetiracetam
BPAD Carbamazepine, Lamotrigine,
Valproate
-
Cognitive problems - Topiramate, Phenobarbitone
Migraine Valproate, Topiramate -
RLS/ PLMS Gabapentin, Pregabalin -
Renal Stones - Topiramate, Zonisamide
Hyponatremia - Oxcarbazeine, Carbamazepine
Prior h/o skin allergy - OXC, CBZ, PHT, LTG, PB, ZSN
Choosing AEDs based on comorbidities.

35. Perucca E, Br J Clin Pharmacol, 2005

36. Perucca E, Br J Clin Pharmacol, 2005

37. Treatment
• Epilepsy may be more easily controlled in the elderly (?).
• Choice of AED is based of tolerability and safety than efficacy.
• Monotherapy is preferred.
• Start low and increase dose slowly.
• Monitor for adverse effects with drug levels and metabolic
parameters.
• Adherence must be ensured (cognitive issues, bedridden pts).
• Therapeutic window is narrower than in younger patients.

38. Peri-procedural advice
• All AEDs to be continued peri-procedurally.
• Change to IV formulation if oral intake is restricted or in case of
colonoscopy etc.
• Avoid medications that reduce seizure threshold: antipsychotics
(chlorpromazine, clozapine), diphenhydramine, atropine,
buproprion, imipenem, meperidine, or tramadol.
• Manage peri-procedural electrolyte disturbances, sleep issues.
• Dose adjustments may be necessary.

39. Refractory Epilepsy
• Video EEG
• MRI brain, PET, SPECT.
• Neuropsychological assessment.
• Seizure freedom after epilepsy surgery in TLE in patients > 60
years of age is similar to those of younger patients.
• However, post surgery benefit in attentional performance was
greater in younger patients, declined in older patients.
• Therefore older patients with intractable epilepsy should not be
denied surgery because of age.

40. Bone health.
• In patients >65 years of age, those taking AEDs are 75% more
likely to experience a fall than those not taking AEDs.
• Patients with epilepsy have double the fracture risk compared to
controls.
• Risk of falls and fractures is more with polytherapy.
• Potent inducers of cytochrome P450 have worst effect on BMD:
PHT, PB, CBZ.
• Even 1 year of PHT monotherapy reduced BMD significantly.
• VPA has mild negative effects on bone health.

41. Conclusion
• Elderly have highest incidence and prevalence of seizures/epilepsy.
• Acquired causes are most likely.
• All seizures are to be treated as focal onset seizures+/- generalisation.
• Epilepsy in elderly requires detailed evaluation.
• Cryptogenic or remote symptomatic seizures require therapy.
• Levetiracetam, Lamotrigine are the most suitable AEDs.
• Patients should be monitored, especially for bone health.
• Epilepsy surgery is an option in selected patients.

42. THANK YOU