Vitamin Deficiencies That Cause Seizures and Their Treatment
Several vitamin deficiencies can cause seizures, with vitamin B6 (pyridoxine), vitamin B12, and vitamin D deficiencies being the most clinically significant. Treatment involves appropriate supplementation of the specific deficient vitamin.
Vitamin B6 (Pyridoxine) Deficiency
Clinical Presentation
- Epileptiform convulsions/seizures
- Peripheral neuropathy
- Confusion and depression
- Dermatitis with cheilosis and glossitis
- Microcytic anemia
- Motor ataxia and weakness
- Loss of deep tendon reflexes 1
High-Risk Populations
- Alcoholics
- Renal dialysis patients
- Elderly individuals
- Post-operative patients
- Patients with infections or critical illness
- Pregnant women
- Patients on certain medications (isoniazid, penicillamine, anti-cancer drugs, corticosteroids, anticonvulsants) 1
- Patients with chronic liver disease 2
- Patients with chronic alcoholism 3
Treatment
- For chronic deficiency: Oral vitamin B6 supplementation 50-100 mg daily for 1-2 weeks 1
- For acute deficiency with seizures:
- For isoniazid overdose-induced seizures: 5 g IV (1 g of pyridoxine for each gram of isoniazid ingested, then 1 g IM or IV every 30 min up to 5 g) 1
- Maintenance dose: 1.3-1.7 mg daily for adults 2
Vitamin B12 (Cobalamin) Deficiency
Clinical Presentation
- Seizures (less common than other neurological manifestations)
- Peripheral neuropathy
- Subacute combined degeneration of the spinal cord
- Cognitive impairment
- Megaloblastic anemia 5
High-Risk Populations
- Patients with pernicious anemia
- Strict vegetarians/vegans
- Elderly individuals
- Patients with malabsorption syndromes
- Patients with inflammatory bowel disease 1
Treatment
- For patients with neurological involvement: Hydroxocobalamin 1 mg IM on alternate days until no further improvement, then 1 mg IM every 2 months 1
- For patients without neurological involvement: Hydroxocobalamin 1 mg IM three times weekly for 2 weeks 1
- Maintenance therapy: 1 mg IM every 2-3 months lifelong 1
- Important: Do not administer folic acid alone before treating B12 deficiency, as it may mask B12 deficiency while allowing neurological damage to progress 5, 6
Vitamin D Deficiency
Clinical Presentation
- Seizures (particularly in severe deficiency)
- Hypocalcemia (which can directly cause seizures)
- Muscle weakness
- Bone pain 7
High-Risk Populations
- Patients with limited sun exposure
- Patients with malabsorption syndromes
- Patients with epilepsy (especially those on enzyme-inducing antiepileptic drugs)
- Elderly individuals
Treatment
- Vitamin D supplementation (dosage based on severity of deficiency)
- Normalization of serum 25(OH)D levels has shown anticonvulsant effects with median seizure reduction of 40% in one study 7
- For patients with hypocalcemia due to vitamin D deficiency: Calcium supplementation along with vitamin D 1
Other Relevant Vitamin Deficiencies
Folate Deficiency
- May contribute to seizures, but less commonly than B6, B12, or D deficiencies
- Important: Always check and treat vitamin B12 deficiency before initiating folic acid treatment to avoid precipitation of subacute combined degeneration of the spinal cord 1
- Treatment: Folic acid 5 mg orally daily for a minimum of 4 months 1
Hypocalcemia (Often Related to Vitamin D Deficiency)
- Can trigger seizures at any age
- Treatment: Calcium and vitamin D supplementation 1
Diagnostic Approach for Suspected Vitamin Deficiency-Related Seizures
Measure serum levels of:
- Vitamin B6 (plasma pyridoxal phosphate)
- Vitamin B12
- Folate
- 25-hydroxyvitamin D
- Ionized calcium
- Magnesium
Consider additional risk factors:
- Malnutrition
- Alcoholism
- Malabsorption disorders
- Medication use (anticonvulsants, isoniazid, etc.)
- Renal disease
For vitamin B6 status, plasma pyridoxal 5-phosphate (PLP) is the preferred measurement
Clinical Pearls and Pitfalls
- Vitamin deficiencies should be considered in patients with refractory seizures not responding to conventional antiepileptic drugs 4
- Seizures may paradoxically appear or worsen temporarily after initiation of vitamin B12 treatment in deficient patients 8
- Excessive vitamin B6 supplementation (>500 mg/day) can cause sensory neuropathy 1
- Folic acid supplementation can mask vitamin B12 deficiency while allowing neurological damage to progress 5, 6
- In patients with epilepsy, folic acid may decrease the effectiveness of certain anticonvulsants like phenytoin 6
- Always check both zinc and copper levels when considering zinc or copper replacement, as they affect each other's absorption 1
By systematically evaluating for these vitamin deficiencies and providing appropriate supplementation, seizure control can often be achieved in cases where conventional antiepileptic medications have failed.