Epilepsy Causes: Genetic, Structural, Infectious & Metabolic

by

Epilepsy Causes: A Doctor’s Comprehensive Guide

By Dr. Sagar Rajkuwar, MS-ENT, Nashik, Maharashtra, India. Clinic Website: www.entspecialistinnashik.com

Epilepsy causes - genetic structural infectious metabolic immune doctor guide

Table of Contents

Introduction & Quick Answer

Quick Answer: Epilepsy causes fall into six ILAE categories: genetic (channelopathies, syndromes like Dravet, juvenile myoclonic epilepsy), structural (stroke, head injury, tumour, cortical dysplasia, hippocampal sclerosis), infectious (neurocysticercosis, bacterial meningitis, herpes encephalitis, TB), metabolic (hypoglycaemia, uraemia, mitochondrial disease), immune (NMDA-receptor encephalitis, LGI1 antibodies), and unknown. In children, genetic and structural causes dominate; in adults, head injury, stroke, and infection; in the elderly, stroke, dementia, and tumours. India has a uniquely high burden of neurocysticercosis and tuberculous meningitis as epilepsy causes.

Patients and families often ask me “why did epilepsy happen?” The honest answer: in 30–40% no specific cause is found even after a full workup, but modern imaging and genetic testing can identify a cause in the remaining 60–70%. This guide draws on WHO, CDC, NHS, NICE, ILAE, American Academy of Neurology, and the Indian Epilepsy Society.

The 2024 ILAE Aetiology Framework

The International League Against Epilepsy classifies all epilepsy causes under six headings:

  1. Genetic
  2. Structural
  3. Infectious
  4. Metabolic
  5. Immune
  6. Unknown

A patient can have more than one — for example, a child with Dravet syndrome has both a genetic cause (SCN1A mutation) and often a structural correlate.

Genetic Epilepsy Causes

Genetic epilepsy causes account for ~30% of all cases, especially childhood-onset epilepsies.

  • Idiopathic generalised epilepsies: juvenile myoclonic epilepsy, childhood absence epilepsy, juvenile absence epilepsy
  • Dravet syndrome (SCN1A mutations)
  • Lennox-Gastaut syndrome (various genes)
  • Ohtahara syndrome
  • Benign familial neonatal epilepsy (KCNQ2/3)
  • Autosomal dominant nocturnal frontal lobe epilepsy (CHRNA4)
  • Tuberous sclerosis complex (TSC1, TSC2)
  • Rett syndrome (MECX2)
  • CDKL5 deficiency
  • Angelman syndrome
  • Mitochondrial epilepsies (MELAS, MERRF)
  • Fragile X syndrome

Structural Epilepsy Causes

Stroke

Post-stroke epilepsy affects 5–10% of stroke survivors — leading cause of new epilepsy > 60. Cortical strokes carry highest risk; haemorrhagic strokes higher than ischaemic.

Head Injury

  • Mild TBI: 2× baseline risk
  • Moderate TBI: 7×
  • Severe TBI: 29×
  • Penetrating injury: 50% develop seizures
  • Risk persists for 10+ years

Brain Tumour

  • Low-grade gliomas, meningiomas, metastases
  • Seizures as presenting feature in ~30%
  • Dysembryoplastic neuroepithelial tumour (DNET), ganglioglioma — classic epileptogenic

Cortical Malformations

  • Focal cortical dysplasia — leading paediatric surgical cause
  • Lissencephaly, pachygyria, polymicrogyria
  • Hemimegalencephaly
  • Band heterotopia
  • Schizencephaly

Hippocampal Sclerosis

Scarring of the medial temporal lobe — commonest cause of adult drug-resistant focal epilepsy. Often linked to childhood febrile status epilepticus.

Vascular Malformations

  • Arteriovenous malformations (AVM)
  • Cavernous malformations (cavernomas)
  • Developmental venous anomalies (rarely)

Infectious Epilepsy Causes

  • Neurocysticercosis (pork tapeworm larvae) — single commonest cause worldwide, major in India, Latin America, sub-Saharan Africa
  • Bacterial meningitis
  • Tuberculous meningitis
  • Herpes simplex encephalitis
  • Japanese encephalitis
  • Cerebral malaria
  • HIV with opportunistic infections
  • Toxoplasmosis
  • Rabies
  • Zika virus (microcephaly-related)
  • Post-infectious epilepsy following any CNS infection

Metabolic Epilepsy Causes

  • Hypoglycaemia
  • Hyponatraemia, hypernatraemia
  • Hypocalcaemia, hypomagnesaemia
  • Uraemia
  • Hepatic encephalopathy
  • Mitochondrial disorders
  • Pyridoxine (B6) dependency
  • Glucose transporter deficiency (GLUT1)
  • Non-ketotic hyperglycinaemia
  • Porphyria
  • Thyroid storm
  • Drug withdrawal (alcohol, benzodiazepines)
  • Drug toxicity (tramadol, bupropion, isoniazid without pyridoxine)

Immune / Autoimmune Epilepsy Causes

  • NMDA-receptor encephalitis
  • LGI1 antibody encephalitis
  • CASPR2, GABA-B, AMPA antibodies
  • Rasmussen encephalitis
  • Hashimoto encephalopathy
  • Paraneoplastic syndromes
  • Multiple sclerosis
  • Systemic lupus erythematosus

Unknown Causes

Despite modern workup, ~30% of epilepsy causes remain unknown. This category shrinks each year as genetic panels and 3-Tesla MRI improve.

Childhood Epilepsy Causes

  • Birth asphyxia / hypoxic-ischaemic encephalopathy
  • Intrauterine infections (TORCH)
  • Prematurity-related brain injury
  • Genetic syndromes (as above)
  • Cortical malformations
  • Metabolic errors
  • Febrile seizures evolving into epilepsy (small percentage)
  • Neurocutaneous syndromes (tuberous sclerosis, Sturge-Weber)
  • Vaccine-preventable infection sequelae

Adult-Onset Epilepsy Causes

  • Head injury
  • Stroke
  • Brain tumour
  • CNS infection (bacterial, viral, parasitic)
  • Alcohol withdrawal
  • Drug toxicity
  • Autoimmune encephalitis
  • Multiple sclerosis
  • Previously undiagnosed genetic epilepsy manifesting late

Elderly-Onset Epilepsy Causes

  • Stroke (leading cause)
  • Alzheimer’s and other dementias
  • Brain tumour (primary or metastatic)
  • Chronic subdural haematoma
  • Metabolic derangements
  • Drug toxicity (tramadol, antidepressants, antibiotics)
  • Alcohol withdrawal

Seizure Triggers (Not True Epilepsy Causes)

Triggers precipitate seizures in people with epilepsy but are not the underlying cause:

  • Sleep deprivation (single biggest trigger)
  • Missed medication
  • Alcohol excess or withdrawal
  • Fever and infection
  • Flashing lights (3–5% with photosensitive epilepsy)
  • Hormonal changes (catamenial epilepsy)
  • Stress
  • Dehydration
  • Hypoglycaemia
  • Specific sensory stimuli (reflex epilepsy — reading, hot water, music)

Indian Context: Neurocysticercosis & TB

  • Neurocysticercosis accounts for 30–50% of adult-onset focal epilepsy in India
  • Tuberculous meningitis and tuberculoma major contributors
  • Birth asphyxia a leading childhood cause
  • Treatment gap ~70%
  • HLA-B*1502 screening before carbamazepine
  • Access to video-EEG and MRI improving but still unequal

Diagnostic Workup to Find the Cause

  • Detailed history including birth, development, head injury, infections, family
  • Neurological exam
  • Routine EEG; sleep-deprived or 24-h ambulatory if normal
  • MRI brain with epilepsy protocol (preferably 3 T)
  • CT if haemorrhage, tumour, calcification suspected (cysticercosis)
  • Blood: glucose, electrolytes, calcium, magnesium, LFT, renal function
  • Autoimmune encephalitis panel if indicated
  • Genetic panels (next-generation sequencing) for early-onset or syndromic cases
  • Lumbar puncture if CNS infection suspected
  • Video-EEG for drug-resistant cases
  • Functional imaging (PET, SPECT) for surgical workup

Infographic: Epilepsy Causes at a Glance

Epilepsy Causes — ILAE Six Categories

GENETIC • Dravet, JME, absence • Tuberous sclerosis • Channelopathies

STRUCTURAL • Stroke, head injury • Tumour, cortical dysplasia • Hippocampal sclerosis

INFECTIOUS • Neurocysticercosis • Meningitis, encephalitis • TB, HIV, malaria

METABOLIC • Hypoglycaemia • Electrolyte derangement • Mitochondrial disease

IMMUNE • NMDA-R encephalitis • LGI1, CASPR2 antibodies • Rasmussen, SLE

UNKNOWN • ~30% of cases • Shrinking yearly as • genetics & MRI improve

INDIAN CONTEXT Neurocysticercosis + TB meningitis = 40-50% of adult-onset focal epilepsy

WORKUP: EEG · 3T MRI · bloods · LP · genetic panel · autoantibodies Finds a cause in 60-70% of patients

Latest 2024–2026 Evidence

  • 2024 ILAE position paper on genetic testing recommends broad gene-panel testing for all early-onset epilepsies.
  • Autoantibody-mediated epilepsies increasingly recognised — treatable with immunotherapy.
  • 3-Tesla MRI with epilepsy protocol halves “non-lesional” cases.
  • Air pollution and heat waves (2024 Lancet study) linked to higher seizure rates.
  • Post-COVID new-onset epilepsy noted but rare.
  • Global rollout of taenia solium control reduces neurocysticercosis incidence (WHO 2026).

Myths vs Facts

Myth Fact
Epilepsy is caused by evil spirits It is a medical brain disorder
All epilepsy is inherited Only ~30% has a genetic basis
Vaccines cause epilepsy No causal link; vaccination prevents infections that do cause epilepsy
Head massage can cure epilepsy No scientific basis
Everyone with epilepsy has brain damage Many have normal imaging
Stress alone causes epilepsy Stress is a trigger, not a cause

10 Frequently Asked Questions

Q1. What is the most common cause of epilepsy?

Worldwide: idiopathic (unknown); in India: neurocysticercosis is a leading identifiable cause.

Q2. Can epilepsy be inherited?

Yes — several syndromes have Mendelian or polygenic inheritance.

Q3. Does a head injury always cause epilepsy?

No — risk depends on severity: mild TBI 2×, severe TBI 29×.

Q4. Can infection cause epilepsy?

Yes — meningitis, encephalitis, neurocysticercosis, TB, malaria all can.

Q5. Can brain tumours cause epilepsy?

Yes — seizures are the first sign in ~30% of brain tumours.

Q6. Is epilepsy caused by stress?

Stress triggers seizures in people with epilepsy but does not cause the underlying condition.

Q7. Can babies be born with epilepsy?

Yes — genetic syndromes, birth asphyxia, and brain malformations are examples.

Q8. Does alcohol cause epilepsy?

Alcohol withdrawal causes seizures; chronic heavy use raises the risk of epilepsy.

Q9. Can vaccines cause epilepsy?

Rare febrile seizures with some vaccines; no evidence for causing chronic epilepsy.

Q10. Is epilepsy more common in some countries?

Yes — low- and middle-income countries have higher rates due to perinatal, infectious, and traumatic causes.

Summary

The six ILAE categories of epilepsy causes are genetic, structural, infectious, metabolic, immune, and unknown. Modern workup (3T MRI, autoantibody panels, genetic sequencing) identifies a cause in 60–70% of patients. In India, neurocysticercosis and tuberculous meningitis remain top identifiable causes. Preventing head injury, controlling infections, perinatal care, and vaccination can reduce the burden of epilepsy worldwide.

Conclusion

Finding the cause of epilepsy guides treatment and prognosis. See a neurologist early, request appropriate imaging and lab tests, and ask about genetic testing where relevant. For patients and families in Nashik, I offer in-clinic consultation at www.entspecialistinnashik.com.

📞 ENT & Health Consultation
Dr. Sagar Rajkuwar (MS-ENT)
Prabha ENT Clinic, Ambad, Nashik
📱 7387590194 | 9892596635
🌐 www.entspecialistinnashik.com

References

Related Articles on Healthuseful

External Links

Medical Disclaimer: This article is for informational purposes only and does not substitute professional medical advice. Please consult a qualified healthcare provider for diagnosis and treatment.

Written by Dr. Sagar Rajkuwar, MS-ENT. Clinic: www.entspecialistinnashik.com | Nashik, Maharashtra, India | For appointments visit the clinic website.