What are the causes of tonic-clonic seizures in a patient with no specified demographic or medical history?

Causes of Tonic-Clonic Seizures

Tonic-clonic seizures arise from either primary generalized epilepsy syndromes or secondary generalization from focal seizures, with precipitating factors including metabolic disturbances (especially hypocalcemia), structural brain abnormalities, medications, genetic conditions, and acute symptomatic triggers.

Primary Etiologic Categories

Epilepsy Syndromes

Idiopathic Generalized Epilepsy (IGE)

• Primary generalized tonic-clonic seizures occur in several IGE syndromes including juvenile myoclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy, and epilepsy with grand mal seizures on awakening 1
• Epilepsy with generalized tonic-clonic seizures alone (GTCA) represents a common IGE syndrome with median age of onset at 17 years 2
• These syndromes have genetic underpinnings, with family history being a clinical finding that may suggest seizure etiology 3

Focal Epilepsy with Secondary Generalization

• Secondarily generalized tonic-clonic seizures arise from focal onset seizures that spread to involve both hemispheres 4
• Antecedent seizures include simple partial, complex partial, or simple partial evolving to complex partial seizures before generalization 4
• Multiple cortical and subcortical routes of spread exist, explaining the heterogeneity in clinical presentation 4

Metabolic and Electrolyte Disturbances

Hypocalcemia

• Hypocalcemia can trigger seizures at any age, even in patients with no prior history of hypocalcemia or seizures 3, 5
• This is particularly important in conditions like 22q11.2 deletion syndrome where underlying parathyroid dysfunction predisposes to hypocalcemia throughout life 3
• Hypocalcemic seizures may resolve with calcium and vitamin D supplementation alone 5

Other Electrolyte Abnormalities

• Hyponatremia and other electrolyte disturbances are common seizure precipitants, especially in elderly patients 5
• Hypoglycemia, hypomagnesemia, and renal dysfunction can all lower seizure threshold 5

Structural Brain Abnormalities

Cortical Malformations

• Polymicrogyria, periventricular nodular heterotopia, and cortical dysplasia can cause seizures including tonic-clonic types 3
• Brain imaging with MRI is indicated when structural abnormalities are suspected 3

Acute Symptomatic Causes

Precipitating Events

• Fever, cerebral ischemia, hypoxia, and surgical procedures can trigger seizures 3
• Infection, particularly with aspiration pneumonia, represents an acute symptomatic seizure trigger 5
• Medications, including antipsychotics, can lower seizure threshold 3

Metabolic Conditions

• Hyperprolinemia has been identified as a potential precipitant in certain genetic syndromes 3

Genetic and Syndromic Conditions

22q11.2 Deletion Syndrome

• Lifetime prevalence of epilepsy is 5-7% in this population, far exceeding the general population rate of 0.5-1.0% 3
• Both generalized tonic-clonic seizures and focal seizures with dyscognitive features occur 3
• Patients have lowered seizure threshold due to the underlying genetic condition 6

Medication Non-Compliance

• Non-compliance with antiepileptic medications is a major precipitant of breakthrough seizures in patients with established epilepsy 5

Important Clinical Distinctions

Differentiating from Syncope

Key Distinguishing Features:

• In true tonic-clonic seizures, movements are prolonged and their onset coincides with loss of consciousness, whereas in syncope any tonic-clonic movements are brief (<15 seconds) and start after loss of consciousness 3
• Seizures typically present with prolonged post-ictal confusion, tongue biting (on the side of tongue), and aching muscles, while syncope has immediate return to clearheadedness 3
• Auras such as epigastric rising sensation or unusual smells suggest seizures, while nausea, lightheadedness, and blurred vision suggest syncope 3

Status Epilepticus as a Complication

• Status epilepticus is defined as seizure activity lasting more than 5 minutes or recurrent seizures without return to baseline, with mortality rates of 5-22% if untreated 5
• Generalized convulsive status epilepticus represents a dynamic state with progression from overt to subtle clinical manifestations if untreated 7

Common Pitfalls

• Overlooking hypocalcemia: Always check ionized calcium in patients with new-onset seizures, as this is a reversible cause that may not require long-term antiepileptic therapy 5
• Misdiagnosing syncope as epilepsy: The consequences of falsely diagnosing epilepsy are significant; when uncertain, it is better to postpone the diagnosis than to label incorrectly 3
• Ignoring medication effects: Antipsychotics and other medications can precipitate seizures in susceptible individuals 3
• Missing structural lesions: While imaging is not indicated for uncomplicated syncope, it should be performed when seizures are suspected based on clinical features 3