What are the different types of seizure disorders and their treatments?

Classification of Seizure Disorders

Seizures are classified into three primary categories based on their origin: focal onset, generalized onset, or unknown onset, as established by the International League Against Epilepsy (ILAE) 2017 classification system. 1

Primary Classification Framework

The ILAE classification system operates on an operational basis rather than fundamental mechanisms, since the basic mechanism of epileptic seizures remains incompletely understood. 1 This classification is critical because proper diagnosis, treatment selection, and prognostication all depend on correct seizure identification. 1, 2

Three Main Categories by Onset

• Focal onset seizures arise within networks of a single cerebral hemisphere and may remain localized or subsequently become more widely distributed. 1, 2, 3

• Generalized onset seizures rapidly affect both hemispheres and both sides of the body from onset, even when caused by a focal lesion. 1, 2, 3

• Unknown onset seizures are classified when the origin cannot be determined but may still exhibit features that can be characterized. 2

Focal Onset Seizures: Detailed Classification

Focal seizures can be further characterized along two key dimensions: 1

By Awareness Level

• Focal aware seizures (previously "simple partial"): consciousness is preserved throughout the seizure. 1
• Focal impaired awareness seizures (previously "complex partial"): awareness is impaired during any segment of the seizure. 1

By Motor vs. Nonmotor Features

Motor onset focal seizures include: 1, 4

• Atonic (loss of muscle tone)
• Automatisms (repetitive purposeless movements)
• Clonic (rhythmic jerking)
• Epileptic spasms
• Hyperkinetic (excessive movement)
• Myoclonic (brief muscle jerks)
• Tonic (sustained muscle stiffening)

Nonmotor onset focal seizures manifest as: 1, 4

• Autonomic dysfunction
• Behavior arrest
• Cognitive impairment
• Emotional symptoms
• Sensory disturbances

Focal to Bilateral Tonic-Clonic

• Focal seizures can evolve to bilateral tonic-clonic seizures (previously termed "secondary generalization"), where the seizure starts focally then propagates to both hemispheres. 1, 3, 4

Generalized Onset Seizures: Detailed Classification

Generalized seizures engage bilateral brain networks from onset and are subdivided into motor and nonmotor types. 1, 2

Generalized Motor Seizures

• Tonic-clonic (grand mal): the classic convulsive seizure with stiffening followed by rhythmic jerking. 1, 2
• Tonic: sustained muscle stiffening without the clonic phase. 1
• Clonic: rhythmic jerking without initial tonic phase. 1
• Myoclonic: brief, shock-like muscle jerks. 1
• Myoclonic-tonic-clonic: myoclonic jerks followed by tonic-clonic activity. 4
• Myoclonic-atonic: myoclonic jerks followed by loss of muscle tone. 4
• Atonic (drop attacks): sudden loss of muscle tone causing falls. 1
• Epileptic spasms: brief flexion or extension movements. 1, 4

Generalized Nonmotor Seizures (Absence)

• Typical absence (petit mal): brief staring spells with abrupt onset and offset, usually lasting seconds. 1, 4
• Atypical absence: similar to typical but with more gradual onset/offset and often longer duration. 1, 4
• Absence with eyelid myoclonia: absence seizures with prominent eyelid fluttering. 4
• Myoclonic absence: absence seizures with rhythmic myoclonic jerks. 4

Important caveat: Absence seizures (petit mal) do not appear to be controlled by carbamazepine, which is effective for other seizure types. 5

Structural and Etiologic Associations

Focal Seizures and Structural Lesions

Certain seizure types are likely associated with structural brain lesions, including: 1, 3

• Tumors
• Infection
• Infarction
• Traumatic brain injury
• Vascular malformations
• Developmental abnormalities (polymicrogyria, focal cortical dysplasia, periventricular nodular heterotopia, hippocampal malrotation) 1
• Seizure-associated brain pathology

Trauma-Related Seizures

Seizures related to trauma subdivide into: 1

• Immediate seizures: secondary to the force of injury itself
• Late seizures: occurring later, more commonly associated with structural causes

Provoked/Acute Symptomatic Seizures

Seizures may be secondary to metabolic or systemic disturbances: 1

• Hypocalcemia (can cause or worsen seizures and movement disorders)
• Hypomagnesemia
• Fever
• Medications
• Stroke

Treatment Considerations by Seizure Type

Focal Seizures

Treatment is tailored to seizure type and contributing conditions, similar to idiopathic epilepsy. 1 Carbamazepine is indicated for partial seizures with complex symptomatology (psychomotor, temporal lobe), with these patients showing greater improvement than those with other seizure types. 5

Generalized Tonic-Clonic Seizures

Carbamazepine is indicated for generalized tonic-clonic seizures and mixed seizure patterns. 5

Myoclonic Seizures

Levetiracetam is specifically indicated for myoclonic seizures in patients with juvenile myoclonic epilepsy. 6 Phenytoin is often ineffective for myoclonus. 7 Alternative antimyoclonic drugs include clonazepam, sodium valproate, and levetiracetam. 7

Primary Generalized Tonic-Clonic Seizures

Levetiracetam is indicated for primary generalized tonic-clonic seizures in patients 6 years and older with idiopathic generalized epilepsy. 6

Clinical Recognition and Diagnostic Approach

Key Distinguishing Features

• The presence of any focal feature to a seizure is independently associated with clinically relevant abnormalities on neuroimaging, making recognition critical. 3
• Focal seizures have a recurrence rate up to 94%, considerably higher than generalized seizures at 72%. 3
• Symmetrical and synchronous movements indicate epilepsy, whereas asymmetrical and asynchronous movements suggest syncope. 7
• Few movements (approximately 10) make syncope more likely; many movements ("cannot count") indicate epilepsy. 7
• Loss of consciousness <30 seconds suggests syncope; duration >1 minute suggests epileptic seizure (mean 74-90 seconds for seizures versus 20 seconds for syncope). 7

Imaging Recommendations

• Non-contrast CT has a central role in emergent acute seizures to rapidly identify structural pathology requiring immediate intervention, including intracranial hemorrhage, stroke, vascular malformation, hydrocephalus, and tumors. 1, 3
• MRI with dedicated epilepsy protocols is the most sensitive and specific anatomic imaging technique for intractable seizures (sensitivity 84%, specificity 70%) and should be the primary imaging modality for newly diagnosed seizures. 3
• MRI is rarely indicated in neurologically normal patients with generalized seizures because the rate of positive findings is low given their genetic basis (only 2% of low-risk patients had abnormal MRI findings). 2, 3

Important Treatment Caveats

Behavioral and Psychiatric Side Effects

Levetiracetam is associated with behavioral symptoms including agitation, anxiety, depression, hostility, and nervousness across all seizure types. 6 In partial onset seizures, 37.6% of levetiracetam-treated patients experienced behavioral symptoms compared to 18.6% of placebo patients. 6

Withdrawal Precautions

Antiepileptic drugs, including levetiracetam, should be withdrawn gradually to minimize the potential of increased seizure frequency. 6