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.

At the study entry (T0) DSE, DRE, and NDE will undergo cognitive evaluations (investigating the main cognitive domains), neurological examinations, and 32channel EEG. DRE and NDE patients will undergo the same clinical, cognitive and 32-channel EEG evaluations at T1 (6 months) and T2 (12 months). DSE patients will be tested only at baseline and they will not undergo longitudinal evaluations.

ASM therapy and seizure frequency will be recorded for DRE and NDE patients in a dedicated database at T0, T1 and T2 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. The quality of sleep during the night previous to the exam will be investigated by the recording technician. Standard clinical procedures will be implemented in the acquisition protocol.

Cognitive evaluations will be performed by an experienced neuropsychologist. The following domains will be assessed: global cognition, memory, language, attention, executive functions, visuospatial abilities, mood and behavior. Moreover, for the assessment of quality of life, the 12-item Short Form Survey (SF-12) will be administered to DSE patients at baseline, and to NDE patients and DRE at baseline and at the follow-up.

Clinical and cognitive data will be exported and analyzed through SPSS and/or R software afterwards. All demographic, personal and clinical information will be codified.

EEG will be stored in a digital archive and on CDs, and then uploaded on dedicated PCs and Linux stations in order to perform the analyses

Inclusion Criteria:

• Inclusion criteria for all study subjects:

  • 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.

• Inclusion criteria for DRE patients:

  • 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).

• Inclusion criteria for DSE patients:

  • 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).

• Inclusion criteria for NDE patients:

  • new diagnosis of focal cryptogenic epilepsy (<3 months)
  • not more than 1 ASM tested
  • available brain MRI (<3 months)

Exclusion Criteria:

• 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

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.