Inclusion Criteria:

Cohort A will consist of epilepsy of unknown cause (high pretest probability):

• ≥ 18 years of age.
• Focal epilepsy diagnosis.
• Onset of epilepsy after age 5.
• No known cause of epilepsy OR presence of hippocampal sclerosis on MRI and;
• Brain MRI completed prior to enrollment.

Cohort B will consist of epilepsy of known cause (medium pretest probability):

• Age above 18.
• Focal epilepsy diagnosis.
• Known cause of epilepsy including any of the following:
  • confirmed viral;
  • bacterial or parasitic CNS infection;
  • traumatic brain injury, stroke;
  • intraventricular hemorrhage;
  • hypoxic-ischemic encephalopathy;
  • neurocutaneous syndrome;
  • confirmed inborn error of metabolism;
  • confirmed genetic and chromosomal developmental encephalopathy;
  • confirmed genetic epilepsy;
  • malformation of cortical development;
  • neoplasia;
  • neurodegenerative disease.
• Brain MRI completed prior to enrollment.

Cohort C will consist of idiopathic genetic generalized epilepsy (low pretest probability):

• Age above 18.
• Idiopathic generalized epilepsy (juvenile myoclonic epilepsy, juvenile absence epilepsy or generalized tonic-clonic seizures alone).
• Brain MRI completed prior to enrollment.

Exclusion Criteria

Cohort A :

• Contraindication for a lumbar puncture (i.e., intracranial mass, bleeding diathesis, spinal developmental anomalies, or local skin infection involving the lower back).
• Evidence of progressive neurological illness.
• Prior epilepsy surgery.
• Known diagnosis of autoimmune encephalitis.
• Prior treatment with immunosuppressive treatment for neurological symptoms.

Within Cohort A, a sub-cohort with probable autoimmune epilepsy (very high pretest probability - Cohort A-1) will be selected with the following criteria:

• Seizure onset in the last 1 year.
• At least 3 out of the following 6 criteria:
• High frequency of seizures (at least 4/month for the last 3 months);
• Antiepileptic drug (AED) resistant (to at least 2 past and/or current AEDs);
• Comorbid depression and/or psychosis requiring psychotropic medication;
• History of status epilepticus;
• Seizures with autonomic semiology defined as any of the following (on history):
  •     cardiovascular (tachycardia, bradycardia, cardiac arrhythmia);
  •     respiratory (cough, hyperventilation, apnea);
  •     gastrointestinal (epigastric sensation, nausea, vomiting);
  •     thermoregulatory, vasomotor and secretory (fever, piloerection, flushing, hypersalivation, spitting);
  •     genitourinary (urinary urge or incontinence).
•  Fulminant onset of epilepsy characterized by any of the following:
•      status epilepticus;
•      ii. viral prodrome (fever, sore throat, runny nose);
•      iii. cognitive decline noted in the first 3 months following onset of seizures;
•      iv. new onset psychiatric symptoms (depression and/or anxiety and/or psychosis) in the first 3 months following onset of seizures.

Cohort B and C: 

• Contraindication for a lumbar puncture (i.e. intracranial mass, bleeding diathesis, spinal developmental anomalies, or local skin infection involving the lower back).
• Prior epilepsy surgery.
• Known diagnosis of autoimmune encephalitis.
• Prior treatment with immunosuppressive treatment for neurological symptoms.

Eligibility last updated 6/17/22. Questions regarding updates should be directed to the study team contact.