1. EPILEPSY IN THE ELDERLY WOMEN
CONF. DR. CHIRILEANU RUXANDA DANA¹ ²
DR.JURCA PATRICIA²
1.UNIVERSITATEA DE MEDICINĂ ŞI FARMACIE ”VICTOR BABEŞ” TIMIŞOARA
2.SPITALUL CLINIC JUDEŢEAN DE URGENŢĂ ”PIUS BRÎNZEU” TIMIŞOARA

2. EPIDEMIOLOGY
It is the most common serious chronic neurological disorder in the elderly after stroke and dementia
Epilepsy incidence has a peak in the newborn and after 60 years of age
Epilepsy commonly manifests for the first time in older individuals
Epilepsy in the elderly is potentially life threatening
Geriatric epilepsy includes
pre-elderly (<60 years old) epilepsy continuing to
old age stage, and
new-onset epilepsy in the elderly.
Epilepsy, especially late-onset epilepsy, significantly impacts the quality of life of older people and increases the health care resource burden on society.

3. EPIDEMIOLOGY
Studies suggest that the increased incidence of seizures in elderly patients to the frequency of various insults to the brain rather than an increase in susceptibility to epileptogenisis.
Most seizures in the elderly are caused by a focal area of damage to the brain, the most common seizure types are localization related.
Complex partial seizures are the most common seizure type, accounting for nearly 40% of all seizures in the elderly population.
Both simple and complex seizures may spread and develop into generalized tonic-clonic seizures.

4. CAUSES
It is reported that an underlying etiology can be found in nearly 50% of elderly patients
Younger patients with epilepsy often show a genetic cause.
New-onset epilepsy in the elderly is mainly the consequence of accumulated injuries to the brain and other secondary factors.
The most common acquired etiologies of new-onset epilepsy and seizures in the elderly include cerebrovascular diseases, primary neuron degenerative disorders associated with cognitive impairment, intracerebral tumors, and traumatic head injury

5. CAUSES CEREBROVASCULAR DISEASE
Stroke is the leading cause of new-onset epilepsy beyond aged 65 years of age
Post-stroke epilepsy usually develops within 3– 12 months
Epilepsy and seizures are more likely after hemorrhagic than ischemic strokes-lesions involving the cerebral cortex , lesions with venous injury that may influence the cortex
A pragmatic approach for elderly patients developing new-onset seizures should include a thorough assessment for cerebrovascular risk factors.

6. CAUSES CEREBROVASCULAR DISEASE
In general, epilepsy can occur at the time or after stroke, or can be an early clinical manifestation of cerebrovascular diseases. Studies have reported that the risk of developing epilepsy in the first year after a stroke increases by 20 times.
A 12-year follow-up study shows that visual neglect, dysphasia, and stroke subtype (particularly total anterior circulation infarcts), are predictors of poststroke epilepsy.
Epilepsy is mainly due to mechanical stimulation of a stroke lesion, nerve cell degeneration, gliosis around the lesion, and glial scar formation.
Ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage are common risk factors of poststroke epilepsy.

7. Small vessel and microvascular diseases of the CNS are also causes of epilepsy
One confusing factor is that a transient ischemic attack (TIA) will sometimes lead to simple partial seizures whose pattern is similar to the deficit of the TIA.
This may create a diagnostic dilemma and concern that another TIA is occurring.
The major clinical differential feature between a TIA and a simple partial seizure is that of the length of the event. Simple partial seizures rarely last more than a few minutes whereas TIAs last longer

8. CAUSES NEURODEGENERATIVE DISORDERS
Neurodegenerative disorders, such as Alzheimer's disease, increase the risk
Those with Alzheimer's disease onset at a younger age who appeared at highest risk
It is reported that patients with all types of dementias are at a fivefold to tenfold increased risk of epilepsy
Specific epileptogenic mechanism is still uncertain in patients with neurodegeneration; there are several reasons that might be associated with secondary epilepsy in dementia, including β-amyloid deposition, neuronal loss and gliosis, chemical changes, antidementia drugs, and comorbidities

9. CAUSES OF ACUTE SYMPTOMATIC SEIZURES
An acute symptomatic seizure is defined as the first seizure attack in people without epilepsy, occurring in close temporal relationship with an acute CNS insult, including metabolic, toxic, structural, infectious, and inflammation
Sleep deprivation, alcohol consumption, and feeling stressed are the most common factors of provocative seizure.
Acute symptomatic (provoked) seizures are common in the elderly, and often have a reversible cause - acute alcohol withdrawal, metabolic and electrolyte disturbances, such as hyponatremia, hypocalcemia and hypomagnesemia, and infections, either systemic or CNS.
By definition, these are not epilepsy.

10. Certain drugs commonly prescribed to elderly people, such as tramadol, also reduce seizure threshold, and are best avoided.
Older people seem to be more susceptible to the epileptogenic effects of some other drugs, such as antipsychotics,
antidepressants (particularly tricyclics), antibiotics, theophylline, levodopa, thiazide diuretics and even the herbal remedy, ginkgo biloba

11. Acute symptomatic seizure is one of the clinical manifestations of uremic encephalopathy, which is currently considered to be associated with a variety of factors, including toxin metabolites, water and salt electrolyte disorders, acid-base balance disorders, and accumulation of dialysis metabolites
Hyperglycemia and hypoglycemia are commonly seen in elderly patients, and both can result in seizures. Older people using an inappropriate dose of insulin are prone to hyperglycemia or hypoglycemia, resulting in seizures. Blood glucose is the main energy source of brain cells, abnormal glucose leads to a lack of energy supply with reduced oxygen supply to brain cells, resulting in local or diffuse cerebral ischemia

12. Potential unknown causes of new-onset epilepsy in the elderly
Although some of new-onset epilepsies in the elderly show identified etiology, one- third to one-half of geriatric epilepsies still have undetected causes, to date, despite the current advances in technology

13. DIAGNOSIS A clear distinction must be made between
epileptic seizures - those arising from brain pathology - and
non-epileptic seizures (provoked seizures) - those arising within a normal brain due to an alteration in physiology, such as hypoxia.
It is imperative that provoked seizures be ruled out before concluding that the seizure was epileptic.
A thorough history must be obtained, focusing on events of the previous day or days, in order identify any precipitating or predisposing factors that may have led to the onset.

14. An EKG should be utilized in order to rule out possible cardiac conditions.
Laboratory tests for metabolic disorders should be done, as well as a review of prescription drugs, over the counter agents, and natural products being used by the patient.
Unfortunately, many natural products designed to simulate weight loss or improve memory may have pro-convulsant properties.
Further, withdrawal from CNS depressants such as benzodiazepines or alcohol may provoke seizures. Stimulants such as methamphetamine and cocaine may cause convulsions.
Unfortunately, abuse of drugs is not absent in the elderly and a drug screen should be considered.

15. DIAGNOSIS
Seizures in the elderly can be more subtle than in younger people. Complex partial seizures are the most common presentation, although may initially evade diagnosis.
Older patients are more likely to have an extratemporal epileptic focus and so less commonly report the typical olfactory/déjà vu auras or automatisms typical of younger patients. Should an aura be reported, it may be described only as 'dizziness‘.
Atypical presentations may also include altered mental status, periods of staring, unresponsiveness, brief losses of consciousness, inattention, memory lapses or confusion.
Should major seizures occur, their characteristics are similar to those in younger people – important markers being lateral tongue biting, waking in an ambulance or in hospital, or significant injuries, for example, vertebral fractures or shoulder dislocation.
Post-ictal periods may be more prolonged, sometimes for several days.

16. DIAGNOSIS
The diagnosis of epilepsy in the elderly is difficult and too often it is incorrect.
Some common clinical scenarios - may mask or mimic epilepsy.
These include mechanical falls, syncope (especially orthostatic hypotension, but also cardiac arrhythmogenic syncope), confusional states, memory problems and sleep disorders
The main differential diagnoses are syncope (reflex, cardiogenic or orthostatic) and psychogenic attacks.
The clinical history, and if possible an eye- witnessed account of the event is very important.

17. The important items in the history are the circumstances and description of warning features of the event (including aura), of the event itself (including impaired consciousness, the presence or absence of pallor, cyanosis, abnormal movements, tongue biting, urinary incontinence) and of the post-event features (e.g., confusion, headache, drowsiness and Todd's paresis).
A history of trauma, including physical abrasions, such as cuts, bruises and burns, may also be of help.
The history should also include a full list of medications (both prescribed and 'over the counter') and a
detailed medical history, including cardiovascular risk factors (diabetes mellitus, hypertension and smoking) and any other
potential epilepsy causes, such as a previous significant head injury, meningitis, encephalitis and, even in the elderly, a history of an abnormal birth or of febrile convulsions.
A detailed family history may also be relevant.

18. DIAGNOSIS
BLOOD TESTS
ECG
EEG
NEUROIMAGING

19. WOMEN WITH EPILEPSY(WWE)
face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health.
experience changes in seizure frequency and severity in relation to different phases in the reproductive cycle: during puberty, over the menstrual cycle, and during pregnancy and the menopause.
- catamenial epilepsy refers to exacerbation of
seizures during different phases of the menstrual
cycle in women with pre-existing epilepsy

20. WOMEN WITH EPILEPSY
Any changes in endogenous or exogenous hormone levels can affect the occurrence of seizures, either directly or via pharmacokinetic interactions that modify the plasma levels of AEDs
- It is reported that in the menopause,
-40% of WWE can experience a worsening of seizure frequency, where as up to
-27% may go into remission as a result of hormonal changes,
-the frequency of catamenial seizures may increase in the perimenopause and decrease at menopause.
Hormone replacement therapy is significantly associated with increased frequency of seizures in menopausal women.

21. Cytochrome-inducing AEDs are known to affect bone mineral density and are associated with bone disorders such as osteoporosis and fractures during and after menopause. Phenytoin has been found to be associated with decreased levels of bone-specific alkaline phosphatase, as well as increased bone turnover, which can predispose to fractures, especially to the neck of femur .
Topiramate use is associated with low parathyroid hormone levels and increased bone turnover in premenopausal women

22. WOMEN WITH EPILEPSY
Oestrogen is known to have a pro-convulsant (seizure causing) effect for some women, but the amount of oestrogen in hormone replacement therapy (HRT) is small and usually not enough to cause seizures to happen.
However if you take HRT and you do have more seizures than usual, this could be related to the oestrogen in HRT.
Osteoporosis it is more common in women, especially after the menopause when levels of oestrogen start to decrease.

23. WOMEN WITH EPILEPSY
Age of menopause may be reduced with 3 to 4 years in women with uncontrolled epilepsy , due to a possible effect of seizures on hypothalamic function (abnormal gonadotropin secretion ) combined with primary ovarian dysfunction . During perimenopause there is gradual decrease of estrogen and progesterone production, resulting in an elevation of the estrogen-to- progesterone ratio who may lead to exacerbation of seizures .

24. During menopause, about
40% of women report worsening of epilepsy,
27% improve,and
33% have no change
WWE who had a catamenial seizure pattern during their fertile years may have significant seizure worsening during perimenopause and improvement during menopause, implying disappearance of proconvulsant influence of reproductive hormones.
AEDs adjustment may be necessary.

25. WOMEN WITH EPILEPSY
Bone disease and influence on vitamin D metabolism was described with enzyme-inducing drugs (phenytoin, primidone, phenobarbital and carbamazepine) but also with chronic use of valproate, suggesting different mechanisms
The effect of long-term administration of the new AEDs (lamotrigine, gabapentin or levetiracetam) is unknown .
WWE have a 2-6 times greater risk of fractures than in the general population due to:
-natural risk of osteoporosis with ageing and postmenopausal status,
-AED use, particularly EIAEDs,
-frequent falls produced by seizures or  unsteadiness as adverse effect of some AEDs .

26. WWE should have a bone health screen and proper advice Physicians are insufficiently aware of the association AEDs – bone disease. Physicians should investigate: The biochemical markers of bone remodeling (parathormone, serum calcium, 25 OH D); - subclinical AEDs impact may show increased parathormone, decreased serum calcium and decreased 25 OH D. Bone mineral density

27. WOMEN WITH EPILEPSY
Calcium intake of mg/day and vitamin D supplementation at doses up to 2000 IU/day is recommended for all patients on initiation of anticonvulsant therapy. -Treatment with IU/day vitamin D is recommended in osteopenic/osteoporotic patients - HRT is associated with an increase in seizure frequency during menopause, more likely in women with a history of catamenial epilepsy. - A combination of 17-β-estradiol with natural progesterone could be considered in these patients

28. WOMEN WITH EPILEPSY
The interactions between hormones, epilepsy, and the medications used to treat epilepsy are complex, with tridirectional interactions which affect both men and women in various ways.
Abnormalities of baseline endocrine status occur more commonly in people with epilepsy, and are most often described for the sex steroid hormone axis

29. WOMEN WITH EPILEPSY
Premature menopause is characterized by amenorrha, cessation of ovarian function and elevated gonadotropin levels.
This premature ovarian failure occurs more commonly in women with epilepsy
association of lifetime number of seizures with the timing of cessation of reproductive cycling may occur due to disruption of hypothalamic and pituitary function directly by the seizures

30. WOMEN WITH EPILEPSY
Alterations in seizure patterns can occur with other major hormonal shifts, such as during puberty, pregnancy, and perimenopause. Some epilepsy syndromes are first expressed or worsen during puberty . Perimenopause is marked by erratic and frequently high estrogen levels, while

31. Postmenopause is characterized by stable, low estrogen levels
Postmenopause is characterized by stable, low estrogen levels. A retrospective questionnaire study suggested that seizure frequency can increase with perimenopause and can improve once the menopausal transition is complete . This alteration in seizure pattern was more likely to occur in women who experienced a catamenial pattern during their reproductive years.

32. Management
Expertise and clinical acumen are needed to exclude the epilepsy mimics and to take account of the multiple comorbidities and polypharmacy of old age.
Epilepsy management should aim for seizure freedom with minimal side effects and with maintenance of a normal lifestyle
The key to minimizing side effects of AEDs is to start at a low dose and titrate gradually to an effective dose.
AED side effects, such as cognitive disturbance, dizziness, somnolence and osteoporosis, have greater implications to the elderly than to younger patients. Somnolence and cognitive disturbance are common AED side effects and these can contribute to falls and injuries, even if not caused by seizures.

33. Osteoporosis is important in elderly patients and certain AEDs, such as phenytoin, phenobarbital and carbamazepine, may reduce vitamin D by enzyme induction and so can substantially increase an elderly patient's risk of fracture
prophylactic vitamin D and calcium.
Aspects important to the patient, such as associated comorbidities, quality of life issues, medication side effects, driving eligibility, social stigmas, taboos and discrimination.
For these reasons, a multidisciplinary team approach to epilepsy management in the elderly may offer the best health outcomes.

34. MANAGEMENT
it is reasonable to consider prescribing an AED to an elderly patient after one unprovoked seizure, especially if there is a structural lesion on neuroimaging (with a consequent high risk of recurrence) or a high risk of injury from a further seizure.
antiepileptic drug-dose alterations may be required in patients with renal failure, and
bone protection should be considered in elderly people receiving enzyme-inducing drugs

35. given the close association of stroke with epilepsy in the elderly, addressing cardiovascular risk factors in elderly patients presenting with new-onset seizures might include an additional prescription of aspirin and a statin; dose adjustments or an alternative cholesterol-lowering agent may be required if the patient is prescribed an enzyme-inducing antiepileptic drugs
Epilepsy can substantially disrupt quality of life in the elderly, as at any age.
Epilepsy in the elderly undoubtedly contributes to social isolation, withdrawal, anxiety and depression.
treatment of epilepsy in the elderly is about far more than simply controlling seizures and must also focus upon quality of life.

36. ANTIEPILEPTIC DRUGS
Particular care is needed in choosing an AED for someone already taking warfarin: older AEDs, such as phenobarbital, phenytoin and carbamazepine, induce the P450 enzyme pathway and so increase warfarin metabolism.
plasma levels of antiarrhythmic drugs, such as amiodarone, can be decreased by enzyme-inducing AEDs
interaction of amiodarone with phenytoin gives increased plasma concentrations of phenytoin.
Plasma concentrations of digoxin can also be decreased due to concurrent administration of phenytoin
enzyme-inducing AEDs increase the metabolic clearance of β-adrenoreceptor blocking agents, calcium antagonists and verapamil

37. PROGNOSIS
Although there are few published results on epilepsy prognosis in the elderly, the outlook on AEDs is (surprisingly) generally considered good, perhaps better than in younger patients.
One review of patients with epilepsy aged over 65 years demonstrated that 64% were seizure-free at 1 year on their first AED and 84% following further drug manipulations

38. Conclusions
Changes in endogenous or exogenous hormone levels can affect the occurrence of seizures directly as well as indirectly through pharmacokinetic effects that alter the concentrations of antiepileptic drugs.
The underlying structural and physiological brain abnormalities of epilepsy and the metabolic activity of antiepileptic drugs can adversely affect hypothalamic and gonadal functioning
women with epilepsy are at risk of early onset of the menopausal transition.
The mechanism is likely related to hypothalamic- pituitary-gonadal axis dysfunction, producing dysregulation of maturation of ovarian follicles and early loss of follicles available for ovulation
decrease in seizures at menopause

39. Conclusions Difficult diagnosis due to epilepsy mimics
Management is complex due to
Comorbidities in the elderly
Focus upon quality of life
Drug interactions

40. Conclusions
Epilepsy in the elderly is typically associated with anxiety, depression and a low quality of life, and physical comorbidities,
Many older people cope relatively well with epilepsy and other chronic illnesses.
This apparent acceptance may simply reflect a population who has already begun coping and adapting to other illnesses

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