What are the metabolic causes of symptomatic seizures?

Metabolic Causes of Symptomatic Seizures

The most common metabolic causes of symptomatic seizures include electrolyte abnormalities (particularly hyponatremia and hypocalcemia), glucose disturbances, and uremia, which should be promptly identified and corrected to prevent recurrence and improve patient outcomes. 1

Primary Metabolic Causes

• Electrolyte Abnormalities:

  • Hyponatremia - one of the most frequently identified metabolic causes of seizures 1, 2
  • Hypocalcemia - can trigger seizures at any age, even in patients with no prior history 1
  • Hypomagnesemia - particularly common in patients with alcohol-related issues 2
  • Hypernatremia and hypercalcemia - less common but still significant causes 1

• Glucose Disturbances:

  • Hypoglycemia - particularly dangerous and requires immediate correction 2
  • Hyperglycemia - can also precipitate seizures 1

• Renal Dysfunction:

  • Uremia - accumulation of toxic metabolites can lower seizure threshold 1

Secondary Metabolic Causes

• Inborn Errors of Metabolism:

  • Disorders of amino acid metabolism 3
  • Disorders of energy metabolism (mitochondrial disorders) 3
  • Organic acidemias (glutaric aciduria, methylmalonic aciduria, propionic acidemia) 4
  • Medium chain fatty acyl-CoA dehydrogenase deficiency 4
  • Disorders of purine and pyrimidine metabolism 3
  • Congenital disorders of glycosylation 3
  • Lysosomal and peroxisomal disorders 3

• Endocrine Disorders:

  • Hypoparathyroidism - leading to hypocalcemia 5
  • Hypothyroidism - may be associated with or contribute to hypocalcemia 5

Pathophysiological Mechanisms

• Energy Deficit - Metabolic seizures often result from inadequate energy supply to brain tissue 6, 7
• Neurotoxicity - Accumulation of toxic metabolites disrupts normal neuronal function 7
• Altered Neurotransmission - Imbalance between excitatory and inhibitory neurotransmitters 8
• Autointoxication - Accumulation of acyl-CoA compounds that disrupt intermediary metabolism 4

Diagnostic Approach

• Core Laboratory Tests for all patients with seizures:

  • Serum glucose and sodium 2
  • Pregnancy test for women of childbearing age 2

• Extended Testing based on clinical presentation:

  • Complete metabolic panel including calcium, magnesium, and phosphate for patients with:
    • Known renal insufficiency
    • Malnutrition
    • Those taking diuretics 2
  • Drug screen for patients with first-time seizures 2
  • Lumbar puncture for immunocompromised patients or those with fever/meningeal signs 2

Management Principles

• Treat the Underlying Cause rather than initiating long-term antiseizure medications for provoked seizures 1

• Correct Electrolyte Abnormalities:

  • Replace calcium in hypocalcemia
  • Correct sodium abnormalities gradually
  • Supplement magnesium when deficient 1

• For Active Seizures:

  • First-line: Appropriate dosing of benzodiazepines for seizures not self-limiting within 5 minutes 1
  • Second-line: Fosphenytoin, levetiracetam, or valproic acid (similar efficacy of 45-47%) 1

Special Considerations

• Genetic Conditions:

  • Patients with 22q11.2 deletion syndrome have a 4-fold increased risk of epilepsy and require monitoring for hypocalcemia and hypomagnesemia 5
  • For patients with inborn errors of metabolism, levocarnitine may help alleviate metabolic abnormalities by promoting excretion of excess organic or fatty acids 4

• Alcohol-Related Seizures:

  • Should be a diagnosis of exclusion, especially in first-time seizures 2
  • Always check magnesium levels in these patients 2

Prevention Strategies

• Regular monitoring of electrolytes in at-risk patients 1
• Ensuring medication compliance in patients with known epilepsy 1
• Education about avoiding seizure triggers (sleep deprivation, substance use) 1

Remember that metabolic seizures should be particularly considered in cases of unexplained neonatal seizures, refractory seizures, seizures related to fasting or food intake, and seizures associated with other systemic or neurologic features 3.