What is the diagnostic approach to different types of seizures?

Diagnostic Approach to Different Types of Seizures

Initial Classification Framework

The diagnostic approach begins with classifying seizures into three fundamental categories: focal onset, generalized onset, or unknown onset, as this classification directly determines the diagnostic pathway and identifies patients at higher risk for structural brain lesions. 1

Seizure Type Determination

• Focal seizures arise within networks of a single cerebral hemisphere and may remain localized or become widely distributed, characterized by motor or nonmotor onset symptoms with varying levels of awareness 1
• Generalized seizures rapidly affect both hemispheres and both sides of the body simultaneously, subdivided into tonic-clonic, other motor, or nonmotor (absence) types 1
• Unknown onset seizures require further evaluation when initial presentation does not clearly fit focal or generalized patterns 1

Age-Specific Diagnostic Considerations

Neonatal Seizures (0-29 days)

In neonates, an underlying cause can be identified in approximately 95% of cases, making aggressive diagnostic evaluation essential. 1, 2

• Hypoxic ischemic injury is the most common cause (46-65% of cases), with approximately 90% occurring within 2 days of birth 1, 2
• Intracranial hemorrhage and perinatal ischemic stroke account for 10-12% of neonatal seizures 1, 2
• Metabolic abnormalities, infections, and structural malformations must be systematically excluded 1

Pediatric Seizures (1 month to 18 years)

The diagnostic approach in children must distinguish between simple febrile seizures (which rarely require imaging), complex febrile seizures, and afebrile seizures based on clinical presentation and neurologic examination. 1

• Neurologically normal children with primary generalized seizures (e.g., juvenile myoclonic epilepsy, childhood absence) typically have genetic underpinnings and rarely show positive intracranial findings on imaging 1
• Focal seizures in children warrant more aggressive imaging evaluation, with nearly 50% showing positive findings compared to only 6% in generalized seizures 1
• Neurologically abnormal children require comprehensive imaging regardless of seizure type 1

Provoked vs. Unprovoked Seizure Distinction

Determining whether a seizure is provoked (acute symptomatic) or unprovoked is critical, as provoked seizures occur within 7 days of an acute insult while unprovoked seizures occur without acute precipitating factors. 2

Provoked Seizure Etiologies to Evaluate

• Metabolic derangements: Hypoglycemia, hyperglycemia, hyponatremia, hypocalcemia, hypomagnesemia, and uremia 2
• Toxic ingestions: Cocaine, tricyclic antidepressants, antihistamines, theophylline 2
• Acute CNS insults: Stroke, intracranial hemorrhage, traumatic brain injury, CNS infections (meningitis, encephalitis) 2
• Fever in seizure patients warrants strong consideration of CNS infection 2

Unprovoked Seizure Etiologies to Evaluate

• Remote structural lesions: Prior stroke (>7 days), remote traumatic brain injury, malformations of cortical development 2
• CNS mass lesions: Tumors, brain masses 2
• Vascular malformations 2
• Idiopathic/genetic epilepsy syndromes 2

Clinical Examination Priorities

Focal neurologic examination findings have 97% correlation with symptomatic seizures, making detailed neurologic assessment the highest yield clinical tool. 2

• History and physical examination predict most metabolic abnormalities except occasional cases of hypoglycemia and subdural hematomas 2
• Presence of predisposing conditions and focal seizure characteristics are the two clinically significant high-risk indicators of abnormal neuroimaging 1

Electroencephalography (EEG) Role

EEG is the most important laboratory examination for epilepsy diagnosis, though limitations of EEG interpretation must be recognized as it can be normal in patients with epilepsy. 3

• EEG helps distinguish epileptic seizures from nonepileptic attacks 3
• EEG patterns guide syndromic classification and help identify characteristic features of primary generalized epilepsies 1
• EEG findings combined with clinical presentation determine whether imaging is necessary 1

Neuroimaging Decision Algorithm

When Imaging is Usually Appropriate

MRI is the imaging study of choice in nonemergent situations for all patients with epilepsy, except those with typical forms of primary generalized epilepsy with characteristic clinical and EEG features who respond adequately to antiepileptic drugs. 1

• New-onset focal seizures require MRI evaluation 1
• Abnormal neurologic examination mandates imaging 2
• Intractable or refractory epilepsy requires dedicated epilepsy protocol MRI with 3T scanners when possible (sensitivity 84%, specificity 70%) 1
• Neonatal seizures require imaging to identify hypoxic ischemic injury, hemorrhage, or structural malformations 1

When Imaging May Not Be Necessary

• Neurologically normal children with typical primary generalized epilepsy (juvenile myoclonic epilepsy, childhood absence) with characteristic EEG features and adequate response to antiepileptic drugs 1
• Simple febrile seizures in otherwise healthy children 1

Emergent CT Indications

CT has a central role in acute seizure presentations when rapid identification of hemorrhage, stroke, hydrocephalus, or mass lesions requiring neurosurgical intervention is needed. 1

• CT is appropriate when ready access to the patient during scanning is required 1
• CT is less sensitive than MRI for orbitofrontal and medial temporal lesions, with only 30% success in detecting lesions in focal epilepsies compared to MRI 1

Special Population Considerations

HIV/Immunocompromised Patients

HIV patients with new-onset seizures require consideration of CNS toxoplasmosis, lymphoma, cryptococcal meningitis, and HIV encephalopathy, with higher rates of infectious etiologies than immunocompetent patients. 2

Post-Traumatic Seizures

Seizures related to trauma are subdivided into immediate seizures (secondary to force of injury itself) and late seizures (occurring later), requiring different diagnostic and prognostic considerations. 1

Syndromic Classification Approach

After determining seizure type and identifying etiology, attempt syndromic classification to match patients with known epilepsy syndromes, as this determines prognosis and guides treatment selection. 3

• When patients do not match described syndromes, utilize neurobiologic approach with genetic, neurophysiological, and neuropharmacologic knowledge 3
• Reevaluate epilepsy diagnosis, etiology, and seizure-type diagnosis when seizure control is insufficient with first- and second-line antiepileptic drugs 3

Common Diagnostic Pitfalls

• Assuming all seizures require imaging: Typical primary generalized epilepsies with characteristic features rarely show structural abnormalities 1
• Relying solely on CT: CT misses small cortical lesions and has much lower sensitivity than MRI for epileptogenic foci 1
• Missing metabolic causes: While history and physical predict most metabolic abnormalities, hypoglycemia and subdural hematomas can be missed 2
• Overlooking immunocompromised status: These patients have significantly higher rates of infectious etiologies requiring different diagnostic approaches 2