What are the causes and treatment options for seizures in individuals with Down syndrome?

Causes and Treatment of Seizures in Down Syndrome

Seizures in individuals with Down syndrome are primarily caused by hypocalcemia, Alzheimer's disease-related changes, and imbalances in neurotransmission, and should be treated with targeted antiseizure medications based on seizure type while addressing underlying metabolic abnormalities.

Common Causes of Seizures in Down Syndrome

Metabolic Abnormalities

• Hypocalcemia: A major trigger for seizures in Down syndrome, affecting up to 80% of patients at some point in their lifetime 1
• Hypomagnesemia: Often occurs alongside hypocalcemia and can independently trigger or worsen seizures 2
• Thyroid dysfunction: Nearly 1 in 4 adults with Down syndrome require treatment for primary hypothyroidism, which can contribute to seizure risk 2

Neurological Factors

• Alzheimer's disease-related changes: Adults with Down syndrome have a high risk of developing dementia, which significantly increases seizure risk, particularly late-onset myoclonic epilepsy (LOMEDS) 3, 4
• Neurotransmitter imbalance: Paradoxically, enhanced GABA inhibition has been reported to promote seizures in Down syndrome 5
• Structural brain abnormalities: Including malformations of cortical development such as polymicrogyria and focal cortical dysplasia 2

Age-Related Patterns

• Childhood: Infantile spasms, focal seizures, and generalized tonic-clonic seizures are most common 6
• Adulthood: Risk increases significantly after age 40, with over 50% of patients with Down syndrome and Alzheimer's dementia developing epilepsy 4

Diagnostic Approach

Initial Evaluation

• Laboratory testing: Complete metabolic panel focusing on:
  • Calcium and ionized calcium levels
  • Parathyroid hormone
  • Magnesium
  • Thyroid-stimulating hormone
  • Vitamin D levels 2

Neurological Assessment

• Electroencephalography (EEG): Essential for diagnosis and classification of seizure type
  • Abnormal EEG findings are present in 100% of Down syndrome patients with epilepsy 6
  • Common findings include focal changes, spikes, generalized slowing, and in some cases hypsarrhythmia 6

Imaging

• Brain MRI: Recommended when:
  • Focal neurologic deficits are present
  • Seizures are refractory to treatment
  • To rule out structural abnormalities 2

Treatment Strategies

Metabolic Correction

• Calcium management:
  • Daily vitamin D supplementation for all patients
  • Calcium supplementation as needed
  • Calcitriol for severe/refractory hypocalcemia (with endocrinologist consultation) 2
  • Caution against overcorrection which can lead to hypercalcemia and renal issues 2

Antiseizure Medications

• First-line options:

  • Levetiracetam: Particularly effective for generalized seizures and myoclonic epilepsy 7, 3
  • Valproic acid: Commonly used for various seizure types in Down syndrome 3

• Treatment response:

  • Approximately 60% of patients achieve seizure control with appropriate treatment 6
  • Up to 41% may be unresponsive to first-line treatment and require adjunctive therapy 3

Special Considerations for LOMEDS

• Recognition: Characterized by cortical myoclonus and generalized tonic-clonic seizures in adults with cognitive decline 3
• Treatment: Medications that modulate the glutamatergic system may be particularly effective 3

Monitoring and Follow-up

Regular Screening

• Calcium monitoring: Particularly important during periods of biological stress (surgery, illness, pregnancy) 2
• EEG follow-up: To assess treatment response and adjust medications as needed

Cognitive Impact

• Seizures in Down syndrome are associated with more severe cognitive impairment:
  • 78% of children with Down syndrome and epilepsy have moderate to severe cognitive delay
  • 30% of children with Down syndrome without epilepsy have moderate to severe cognitive impairment 7
• Seizure control can lead to slight improvement in intellectual and language capabilities 7

Prevention Strategies

• Regular calcium and vitamin D supplementation
• Thyroid function monitoring
• Early recognition and treatment of Alzheimer's disease symptoms
• Avoidance of triggers: Including alcohol and cola drinks which can worsen hypocalcemia 2

Early identification and appropriate treatment of seizures in Down syndrome is crucial for improving quality of life and cognitive outcomes. A multidisciplinary approach involving neurologists, endocrinologists, and other specialists familiar with Down syndrome is recommended for optimal management.