Epilepsy
Conditions
Keywords
epilepsy, Alzheimer, biomarkers, predictive value
Brief summary
Beyond 60 years, the prevalence of epilepsy is estimated at approximately 1% and increases with age. In these patients, the etiology of epilepsy is unknown in 25% of cases, even up to 55% after 65 years. Although new-onset epilepsy in the elderly is associated with a vascular disease in 50% of cases, the hypothesis of an ongoing neurodegenerative process, including an Alzheimer's disease (AD), is also common. However, investigators do not have any marker that might help to identify the patients who develop epilepsy after 60 years and who might be, despite a normal cognitive functioning, already engaged in the pathophysiological process of AD. A number of data suggest a link between the pathophysiological process of AD and epileptogenesis: (i) a third of patients with epilepsy develops MA, (ii) the occurrence of epilepsy in AD is an aggravating factor for cognition, (iii) in animal models of AD, the relationship between neuronal hyperexcitability and amyloid deposits is bidirectional, the amyloid protein has a pro-seizure effect and the presence of epilepsy increases the amyloid deposits, (iv) in these models, the administration of an antiepileptic drug protects from deterioration of cognition, (v) the close relationship between amyloid and neuronal hyperexcitability might be mediated by the inflammatory processes associated with AD, and particularly the microglial activation which role in epileptogenesis has been shown elsewhere. Investigators hypothesize that in a subgroup of patients who develop epilepsy after 60 years, the occurrence of epilepsy might reflect the presence of an ongoing amyloid pathology. Our goal is to identify through biomarkers of AD in the cerebrospinal fluid of patients who develop an epilepsy after 60 years with normal MRI and normal cognition those at high risk of later developing clinically defined AD. Identifying patients with amyloid pathology which would be expressed through epilepsy before the onset of cognitive dysfunction might help to adapt both the management of seizures and of the cognitive dysfunction.
Interventions
BIOLOGICALprofile of CSF biomarkers of AD
dosage of biomarker of AD
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 60 years * Patients with newly diagnosed epilepsy according to the latest criteria of the International League against Epilepsy. * MMSE ≥ 28/30. * Patients with or without cognitive complaints. * Patients whose brain MRI did not reveal significant abnormalities outside slight cortical atrophy. * Patients in whom the lumbar puncture did not revealed abnormalities suggestive of an infectious disease or a limbic encephalitis. * Patient with adequate visual and auditory skills, an oral and written language in French available to clinical and neuropsychological assessment. * Patient who have given its written consent.
Exclusion criteria
* Previous history of epilepsy before age 60 years. * Patient with against-indication to MRI (pacemaker, ferromagnetic clips, mechanical heart valves, intra-cochlear implants, intraocular foreign body, skin or other) or refusing MRI. * Presence of an abnormality in brain MRI. * Patients with diagnostic criteria for dementia of Alzheimer's disease, vascular dementia, mixed dementia or frontotemporal lobar degeneration. * Patients with autoimmune encephalitis. * Patients under legal protection measure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint was the number of patients in a population of subjects older than 60 years with new-onset epilepsy but without cognitive impairment whose profile of the CSF biomarkers of the AD is suggestive of an AD. | 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| changes in visual recognition memory at 2 years | 2 years | Evolution of DMS 48 score between inclusion and 2 years of follow-up |
| Evolution of DO 80 score | 2 years | Evolution of semantic memory at 2 years: Evolution of DO 80 score between inclusion and 2 years follow-up |
| changes in episodic verbal memory at 2 years | 2 years | Evolution of RL/RI-16 score between inclusion and 2 years of follow-up |
| Evolution of TOP 10 score | 2 years | Evolution of semantic memory at 2 years: Evolution of TOP 10 score between inclusion and 2 years follow-up |
| Changes in monthly frequency of seizures at 2 years | 2 years | Evolution of monthly frequency of seizures between inclusion and 2 years of follow-up |
| Evolution of categorical influences | 2 years | Evolution of semantic memory at 2 years: Evolution of categorical influences between inclusion and 2 years follow-up |
Countries
France
Outcome results
None listed