Diagnosis

Epilepsy

Etiology

Causes of seizures [khg]

• Unknown

• Electrolyte disturbances: hypoglycemia, hyponatremia, hypernatremia, hypocalcemia

• Acute toxic effects: antidepressants, sympathomimetics

• Withdrawal syndromes: ethanol, benzodiazepines

• Reduced compliance to antiepileptic medications

• Sepsis

• CNS infections

• Hypoxic brain injury

• Traumatic brain injury

• Stroke ischemic or hemorrhagic

• Neoplasm

• Inflammatory (lupus cerebritis, anti-NMDA receptor encephalitis, others)

• Fever

• Sleep deprivation

• Genetic predisposition

• Congenital brain malformations

• Brain tumors

• Degenerative conditions (Alzheimer disease)

• Epilepsy: Recurrent unprovoked seizures

  • Genetic susceptibility

  • Chronic pathologic process

Pathophysiology [khg]

1. All individuals have a seizure threshold

2. A sudden imbalance between the excitatory (Glutamate, NMDA) and inhibitory (GABA) forces within the network of cortical neurons --> epileptic seizure

3. The type of seizure depend on the location of the epileptic discharges

Classification

1. Simple focal/partial seizures: seizure with preserved consciousness.

   • Symptoms: deja vu, paresthesia, visual disturbances, illusions, hallucinations, fear, anger, sadness, happiness, nausea, unusual feelings/sensations, aphasia, dysarthria, confusion.

2. Complex focal/partial seizures: excessive and synchronous electrical brain activity in a larger part of the hemisphere that may affect consciousness.

   • Symptoms: aura, deja vu, fear, euphoria, visual disturbances, automatisms, amnesia, asthenia, weakness and fatigue.

3. Generalized seizures: pathologic electrical activity of the whole or a larger portion of the brain and affecting consciousness. Focal/partial seizures may spread from one hemisphere to the other side of the brain and result in a secondarily generalised seizure.

   • Symptoms: generalized tonic-clonic seizure, absence seizure, myoclonic seizure, tonic/clonic/atonic seizure.

Complications [khg]

• Respiratory failure --> Hypoxia

• Brain injury

• Trauma: tongue lacerations or scalp lacerations

Epidemiology

Prevalence per 100.000 [fif][cez]

Incidence per 100.000 [fif][cez]

Approach

• Blood test (prolactin, levels of anticonvulsant agents)

• Blood gas

• Lumbar puncure

• CT caput

• MR caput

• EEG

• Video-EEG

Diagnostic criteria

• The occurrence of at least 2 unprovoked seizures

Treatment

The goal of treatment in patients with epileptic seizures is to achieve a seizure-free status without adverse effects. Monotherapy is desirable.

1. Activity Modification and Restrictions:

   • Driving

   • Ascending heights

   • Working with fire or cooking

   • Using power tools or other dangerous equipment

   • Taking unsupervised baths

   • Swimming

2. Nonpharmacologic Management:

   • Diet

   • Vagal nerve stimulation

   • Implantable neurostimulator

   • Lobectomy and Lesionectomy

3. Anticonvulsant Therapy and their mechanisms: [34r]

   • Blockers of repetitive activation of the sodium channel: Phenytoin, carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, topiramate, cenobamate

   • Enhancers of slow inactivation of the sodium channel: Lacosamide, rufinamide

   • Gamma-aminobutyric acid (GABA)–A receptor enhancers: Phenobarbital, benzodiazepines, clobazam, ganaxolone 

   • N-methyl-D-aspartic acid (NMDA) receptor blockers: Felbamate

   • Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor blockers: Perampanel, topiramate

   • T-calcium channel blockers: Ethosuximide, valproate

   • N- and L-calcium channel blockers: Lamotrigine, topiramate, zonisamide, valproate

   • H-current modulators: Gabapentin, lamotrigine

   • Blockers of unique binding sites: Gabapentin, levetiracetam, perampanel 

   • Carbonic anhydrase inhibitors: Topiramate, zonisamide

   • Other anticonvulsants: Cannabidiol, stiripentol, fenfluramine

4. Treatment of generalized convulsive status epilepticus:

   • Airway, breathing, and circulation

   • 1st line:

     • Lorazepam 4 mg IV; repeat once in 5 to 10 minutes if seizures continue

     • Midazolam 10 mg IM or IV; repeat once in 5 to 10 minutes if seizures continue

     • Diazepam 10 mg IV; repeat once in 10 minutes if seizures continue

   • 2nd line:

     • Fosphenytoin 20PE/kg (up to 1500 phenytoin equivalents)

     • Valproate 40mg/kg (up to 300 mg)

     • Levetiracetam 60/mg (up to 4500 mg)

5. Long term prognosis:

   • Seizure free for 2-5 years --> discontinuing medication

   • Many patients outgrow many epileptic syndromes of childhood

   • The relapse rate for seizures in adults is about 40-50%; for children, it is about 25%

Differential diagnoses

Arrhythmia, Cataplexy, Delirium tremens, Encephalitis, Febrile seizure, Hypoglycemia, Hyponatremia, Meningitis, Migraine, Narcolepsy, Orthostatic hypotension, Panic attack, Paroxysmal dyskinesia, Preeclampsia, Somnambulism, Stroke, Syncope, Transient global amnesia, Transient ischemic attack, Vasovagal syncope