Cognitive Impairment in Drug-resistant and Drug-responsive Focal Cryptogenic Epilepsy

NCT06210022 | Recruiting

• 1 other identifier: FCECOG
• Study Type: observational
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

This is a national monocentric (San Raffaele Hospital - OSR, Via Olgettina, 60, 20132 Milan, Italy) observational low-risk-intervention study, prospective and multiparametric (clinical, EEG, neuropsychological evaluations) study. Patients with a diagnosis of DRE and DSE will be screened to evaluate their eligibility. They will undergo clinical and cognitive assessments in addition to 32channel EEG at baseline (T0). DRE patients will also undergo clinical and cognitive assessments, and 32-channel EEG at 6 months (T1), and 12 months (T2). Patients newly diagnosed with focal cryptogenic epilepsy (NDE) will undergo clinical and cognitive assessments, and 32-channel EEG at baseline (T0), at 6 months (T1), and 12 months (T2). High-definition EEG will be performed to investigate patterns of cortical sources and functional connectivity alteration specific to DRE and DSE and to explore their prognostic value. Longitudinal EEGs will be acquired to explore the evolution of EEG patterns. Cognitive evaluation will be performed by an experienced neuropsychologist. At baseline, DRE, DSE, and NDE patients will undergo a screening and a comprehensive cognitive battery in order to define performance differences among groups. The DRE and NDE group only will perform the same neuropsychological assessment at month 6 and 12 for monitoring the potential progression of cognitive and/or behavioural disturbances in these patients.

Conditions

Epilepsy; Focal Epilepsy

Keywords

epilepsy; focal cryptogenic epilepsy; drug resistant epilepsy

Outcome Measures

Primary Outcomes (7)

• To evaluate the prevalence of cognitive impairment in a population of focal cryptogenic epilepsy patients, comparing subjects diagnosed with DRE (drug resistant epilepsy) and subjects diagnosed with DSE (drug sensitive epilepsy);

  At baseline, DRE and DSE patients will undergo a screening and comprehensive cognitive battery. We will adopt the following scales: EpiTrack screening battery; Rey Auditory Verbal Learning Test and with the Rey's figure recall; Token Test; Paced Auditory Serial Addition Test; Modified Card Sorting Test; Cognitive Estimation Task; Rey's figure copy, Beck Depression Inventory, Dimensional Apathy Scale, 12-item Short Form Survey. The suspect of cognitive impairment (CI) will be defined with EpiTrack screening battery (score \< 32 points indicates CI). This will be confirmed by the comprehensive battery (Level II): Impairment should be present on at least 2 tests. For each test, impairment will be demonstrated with performances below appropriate normative values. Since the classification for CI is not yet defined for epilepsy we will adopt the classification for Parkinson's disease which, as patients with epilepsy, mainly have disturbances in executive, attentive and memory functioning.

  2024-2027

• To monitor the evolution of cognitive performance in DRE patients over a period of one year;

  we evaluate the cognitive state of the patients with the measures and scales listed in "Outcome 1" at 12 months and compare the results to the baseline results.

  2024-2027

• To evaluate whether seizure frequency constitute the main determinant of cognitive impairment;

  We evaluate if patients who reduced the seizure frequence over a period of 12 months showed an improvement in the cognitive assesment, comparing baseline assesment and the follow up assesment at 12 months.

  2024-2027

• To explore EEG-markers of DRE and DSE

  High-density EEGs, with a duration of 20 minutes, will be acquired in resting awake conditions on a computer-based system (Micromed System PLUS, Micromed S.p.A., Mogliano Veneto, Italy) from 32 surface electrodes, placed on an EEG cap according to the international 10/20 system, with linked-ear or mesial prefrontal reference. Vigilance will be continuously monitored in order to avoid drowsiness. EEG will be performed to investigate patterns of cortical sources and functional connectivity alteration in the two different groups od DRE and DSE.

  2024-2027

• To evaluate the entity of cognitive impairment in a population of focal cryptogenic epilepsy patients, comparing subjects diagnosed with DRE (drug resistant epilepsy) and subjects diagnosed with DSE (drug sensitive epilepsy);

  To evaluate the entity of cognitive impairment in DSE with the measures and methods specified in "Outcome 1".

  2024-2027

• To evaluate whether ASM therapy constitute the main determinant of cognitive impairment;

  We evaluate if patients who reduced the number of ASMs medications over a period of 12 months showed an improvement in the cognitive assesment, comparing baseline assesment and the follow up assesment at 12 months.

  2024-2027

• To explore a possible relationship between EEG-markers of DRE and DSE and cognitive impairment

  To explore a possible relationship between EEG-markers of DRE and DSE found as specified in "Outcome 4" and cognitive impairment (evaluated as specified in "Outcome 1").

  2024-2027

Secondary Outcomes (2)

• To evaluate longitudinal evolution of cognitive performances in patients newly diagnosed with focal cryptogenic epilepsy (NDE)

  2024-2027

• To evaluate longitudinal evolution of drug responsiveness in patients newly diagnosed with focal cryptogenic epilepsy (NDE)

  2024-2027

Study Arms (1)

130

Patients with diagnosis of DRE and DSE will be recruited among patients who are regularly followed at our Epilepsy Outpatients Service (OSR). The diagnosis of DRE and DSE focal cryptogenic epilepsy will be based on the most recent sets of criteria of different types of epilepsy. A small group of NDE patients will be also enrolled A population of 30 focal cryptogenic epilepsy patients diagnosed with DRE (drug resistant epilepsy) A population of 90 focal cryptogenic epilepsy patients diagnosed with DRE (drug sensitive epilepsy) 10 patients newly diagnosed for focal cryptogenic epilepsy (NDE) will be recruited too.

Diagnostic Test: Neuropsychological Assessment

Interventions

Neuropsychological Assessment DIAGNOSTIC_TEST

Cognitive evaluation and clinical monitoring of seizure frequency

130

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients with diagnosis of DRE and DSE will be recruited among patients who are regularly followed at our Epilepsy Outpatients Service (OSR). The diagnosis of DRE and DSE focal cryptogenic epilepsy will be based on the most recent sets of criteria of different types of epilepsy. A small group of NDE patients will be also enrolled.

You may qualify if:

• monolingual native Italian speakers;
• age between 18-60 years;
• normal or corrected-to-normal visual acuity;
• oral and written informed consent to study participation.
• if assuming psychotropic drugs (i.e., benzodiazepines, antipsychotics, antidepressants), they should be at stable dosage for more than 4 weeks.
• diagnosis of focal cryptogenic epilepsy;
• previous failure of at least 2 anti-seizure medication (ASM at adequate dose;
• at least 3 seizures in the last 2 months; • available brain MRI (\<5 years).
• diagnosis of focal cryptogenic epilepsy;
• seizure control obtained after not more than 2 ASM;
• seizure freedom for at least 6 months;
• available brain MRI (\<5 years).
• new diagnosis of focal cryptogenic epilepsy (\<3 months)
• not more than 1 ASM tested
• available brain MRI (\<3 months)

You may not qualify if:

• Age\> 60 years;
• Documented developmental delay;
• Evidence of focal abnormalities at neuroimaging (except of hippocampal sclerosis);
• Neurological degenerative conditions;
• history of other systemic (including systemic neoplasms in the last 3 years and abnormal hepatorenal functions), neurologic, psychiatric diseases, head injury, cardiovascular events, and cerebrovascular alterations;
• alcohol and/or psychotropic drugs abuse

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS San Raffaele

Milan, 20132, Italy

RECRUITING

MeSH Terms

Conditions

Epilepsy; Epilepsies, Partial; Drug Resistant Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Anna Bellini, MD

CONTACT

+390226432154; bellini.anna@hsr.it

Davide Gusmeo Curti, MD

CONTACT

+390226432154; curti.davide@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Massimo Filippi

Study Record Dates

• First Submitted: December 21, 2023
• First Posted: January 18, 2024
• Study Start: June 20, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: June 24, 2024

Record last verified: 2024-06

Locations

IT (1)