Epilepsy Diagnosis

• It is recommended that all patients having a first seizure be referred as soon as possible to a specialist to ensure accurate and early diagnosis and initiation of treatment appropriate to the needs of the patients

Levels of Diagnosing Epilepsy

• Seizure type
• Epilepsy type
• Epilepsy syndrome wherein specific syndromic diagnosis can be made

Seizure Types

Focal Onset

• Only one portion of the brain, typically part of one lobe of one hemisphere, is involved
• Can be subcategorized to aware and impaired awareness
• Can also be subgrouped to with motor and nonmotor signs and symptoms
• Retained awareness is when the patient is aware, even if immobile, of self and environment during the seizure
• Impaired awareness is having any significant impairment of awareness during the course of the seizure 
• Focal aware seizure replaced the previous term simple partial seizure
• Focal impaired awareness seizure replaced the previous term complex partial seizure
• Seizure classification should be based on the earliest prominent motor onset or non-motor onset feature
• New focal onset seizure types include automatisms, autonomic, behavior arrest, cognitive, emotional, hyperkinetic, sensory and focal bilateral tonic-clonic seizures 
• Focal to bilateral tonic-clonic is a special type of seizure that was previously termed partial onset with secondary generalization 

Generalized Onset

• Nearly always consciousness is lost except in myoclonic seizures and clinical features together with electroencephalographic changes indicate involvement of bilateral hemispheres of the brain at the onset of seizure
• Motor seizures are subdivided to:
  • Myoclonic (single or multiple jerks, often upper limbs)
  • Tonic
  • Tonic-clonic
  • Clonic
  • Atonic (sudden loss of head posture, limbs and/or body)
  • Myoclonic-atonic
  • Myoclonic-tonic-clonic
  • Epileptic spasms
• Nonmotor (absence) seizures are subdivided to:
  • Typical
  • Atypical
  • Tonic-clonic
  • Myoclonic
  • Eyelid myoclonia

Unknown Onset

• Onset of seizure may be missed or obscured
• Motor unknown onset seizure can be subgrouped as epileptic spasms (includes infantile spasm) and tonic-clonic
• Nonmotor unknown onset seizure subgroup is behavior arrest

Epilepsy Types

Generalized Epilepsy

• Electroencephalogram shows generalized spike-wave activity
• May have a range of seizure types that include absence, myoclonic, atonic, tonic and tonic-clonic seizures
• Idiopathic/Genetic Generalized Epilepsy
  

• Well-recognized and common subgroup of generalized epilepsy
• It encompass 4 well-established epilepsy syndromes: Childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy and generalized tonic-clonic seizures alone

Focal Epilepsy

• Diagnosis is made on clinical findings together with electroencephalogram findings of focal epileptiform discharges
• Includes unifocal and multifocal disorders as well as seizures involving one hemisphere
• Range of seizure types that can be seen include focal aware seizures, focal impaired awareness seizures, focal motor seizures, focal non-motor seizures, focal to bilateral tonic-clonic seizures

Combined Generalized and Focal Epilepsy

• Patients who have both generalized and focal seizures
• Diagnosis is based on clinical findings with electroencephalogram findings of both generalized spike-wave and focal epileptiform discharges but epileptiform activity is not required for diagnosis

Unknown Epilepsy

• For patients who have epilepsy but the clinician is unable to determine if the epilepsy type is focal or generalized due to insufficient information available

Epilepsy Syndrome

• A cluster of features that incorporates seizure types, electroencephalography findings and imaging features that tend to occur together
• Age-dependent features that is commonly found are age at onset and remission, seizure triggers, diurnal variation and sometimes prognosis
• It serves as a guide to management as it does not have a one-to-one correlation with  an etiologic diagnosis
• Well-recognized syndromes are Childhood absence epilepsy, West syndrome, Dravet syndrome

Determine Etiology

• From the moment that the patient presents with a first epileptic seizure, the clinician should aim to determine the etiology of the patient’s epilepsy
• Determine the disease associated with the epileptic seizure or syndrome
  • Eg neurocutaneous diseases, malformations, tumors, chromosomal anomalies, monogenic Mendelian diseases, etc
• Often the first investigation carried out involves neuroimaging, ideally magnetic resonance imaging if available
  • This enables the clinician to decide if there is a structural etiology for the patient’s epilepsy
• Other etiologies include genetic, infectious, metabolic, immune and unknown

Electroclinical Syndromes and Other Epilepsies

Electroclinical Syndrome

• A complex of clinical features, symptoms and signs defined by a group of electroclinical characteristics
• Classified based on typical age of onset, electroencephalography (EEG) findings, type of seizure, and other characteristics which allow for a specific diagnosis
• One example is electroclinical syndromes arranged by age of onset:
  • Neonatal period: Eg early myoclonic encephalopathy (EME), benign familial neonatal epilepsy (BFNE)
  • Infancy: Eg West syndrome, benign infantile epilepsy, epilepsy of infancy with migrating focal seizures, myoclonic epilepsy in infancy (MEI)
  • Childhood: Eg epilepsy with myoclonic atonic seizures, epilepsy with myoclonic absences, febrile seizures plus (FS+), electrical status epilepticus during slow sleep (ESES)
  • Adolescence to adulthood: Eg juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), epilepsy with generalized tonic-clonic seizures alone, progressive myoclonus epilepsies (PME)
  • Less specific age relationship: Eg reflex epilepsies, familial focal epilepsy with variable foci (childhood to adult)

Distinctive Constellations

• Represent clinically distinct groupings or constellations based on specific lesions or other causes
• Age at presentation is not a defining feature
• Eg Rasmussen syndrome, mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE with HS), hemiconvulsion-hemiplegia-epilepsy, gelastic seizures with hypothalamic hamartoma
• Epilepsies that do not fall into any of these groups can be identified by:
  • Presence or absence of a known metabolic or structural condition
  • Primary means of seizure onset (focal vs generalized)

• History should include but is not limited to: Age of onset, description of attack from patient and an observer, family history, social history, alcohol and drug use, and past medical history including head injury, febrile convulsions, diseases in other organ systems
• A clear history from the patient and an eyewitness to the attack is the most important diagnostic information and should be the mainstay of diagnosis

Seizure Description

• Patient should describe in detail: Frequency of attacks,triggering factors, symptoms before, during and after the attacks, duration of symptoms, injury incurred and incontinence
• Witness should describe in detail: Frequency of attacks, detailed observations before and during the attacks (eg physical symptoms, psychic symptoms and level of consciousness) and symptoms following the attacks

• Visual stimulation (eg photic stimulation), sleep deprivation, hyperventilation, fatigue, stress, alcohol intake

• Detect signs of disorder associated with epileptic seizures (eg sign of head trauma, ear or sinus infection, congenital abnormalities, focal or diffuse neurologic abnormalities, diseases in other organ systems)

• To determine the cause of the seizure or identify potentially treatable conditions or acute symptomatic seizure, the following tests should be done:

• Blood glucose level
• Creatinine, urea nitrogen and electrolytes
• Liver function tests (LFTs)
• Serum Na, Ca and Mg levels
• Blood or urine illicit drug or alcohol determination, if indicated
• Lumbar puncture, when meningitis or encephalitis is suspected

Diagnostic Tests

Electroencephalography (EEG)

• Should be considered as part of routine neurodiagnostic evaluation of an adult who presents with unprovoked seizure that is most likely to recur as epilepsy
  • Ideally, must be performed as soon as possible (within 72 hours post-ictal)
  • May perform provoking maneuvers (eg hyperventilation, photic stimulation, sleep deprivation)
• Helps to determine the presence of epileptiform activity and the type and location of epileptiform activity
• Limitations
  • Abnormal electroencephalography is somewhat common in the elderly, patients with migraine, psychotic illness and those taking psychotropic medication
  • Non-specific electroencephalography abnormalities should not be interpreted as confirming a diagnosis of epilepsy
  • Electroencephalogram may be normal in a number of epileptic patients
  • A normal electroencephalography should not exclude the diagnosis of epilepsy
• Consider video electroencephalography for differential diagnosis of paroxysmal events including epileptic seizures, organic nonepileptic seizures, and psychogenic nonepileptic seizures, classification of seizure types and electroclinical syndromes, quantification of seizures and of interictal and ictal epileptiform discharges, and presurgical evaluation in medically refractory epilepsy patients

Brain Imaging

• Should be considered as part of routine neurodiagnostic evaluation of an adult who presents with an apparent unprovoked first seizure
• Magnetic resonance imaging (MRI) is brain imaging of choice in patients with epilepsy
  • Useful in patients with onset of focal seizure from history, examination or electroencephalography and in those who have continued seizures despite adequate 1st-line antiepileptics/anticonvulsants
  • Recommended to be performed within 6 weeks
  • Special MRI sequences are used to detect cortical dysplasia and mesial temporal sclerosis
• Computed tomography (CT) may be used if urgent assessment of seizures during acute situations is necessary or magnetic resonance imaging is contraindicated
• Interictal FDG-PET scan of the brain is used to locate hypometabolic region of the brain
• Ictal single photo emission computerized tomography (SPECT) is used to locate epileptic focus