Epilepsy & Developmental Neuropathology
What You'll Learn
- Hippocampal sclerosis — the pathology of mesial temporal lobe epilepsy
- Focal cortical dysplasia and the malformations of cortical development (migration/organization defects)
- Neurocutaneous epilepsy substrates (tuberous sclerosis, Sturge-Weber) and Rasmussen encephalitis
- Major neural-tube and posterior-fossa malformations
The neuropathology view of epilepsy substrates & malformations. Clinical epilepsy management lives in the Epilepsy notes.
- Hippocampal sclerosis = neuron loss + gliosis in CA1 and CA4 with relative CA2 sparing (ILAE type 1); commonest surgical substrate for mesial temporal lobe epilepsy.
- Focal cortical dysplasia type II = dysmorphic neurons ± balloon cells (IIb); IIb is usually MRI-visible (cortical thickening, blurred grey-white junction, transmantle sign), whereas FCD type I is often MRI-subtle.
- Cortical tuber (tuberous sclerosis) is histologically like FCD IIb — balloon cells + dysmorphic neurons + disrupted lamination.
- Sturge-Weber = leptomeningeal capillary-venous angiomatosis → cortical laminar “tram-track” calcification and atrophy.
- Rasmussen encephalitis = unihemispheric T-cell inflammation, microglial nodules, neuronophagia → progressive hemiatrophy.
Hippocampal Sclerosis
The hallmark of drug-resistant mesial temporal lobe epilepsy. Segmental pyramidal-neuron loss with reactive astrogliosis; associated granule-cell dispersion and mossy-fiber sprouting.
| ILAE type | Neuron loss | Note |
|---|
| Type 1 (classic) | CA1 and CA4 predominant, with gliosis; CA2 relatively spared | Most common; best surgical outcome |
| Type 2 | CA1-predominant | Atypical |
| Type 3 | CA4-predominant | Atypical |
Focal Cortical Dysplasia
| FCD (ILAE) | Pathology | Association |
|---|
| Type I | Abnormal radial/tangential lamination only; no abnormal cells | Often MRI-subtle |
| Type IIa | Dyslamination + dysmorphic neurons (enlarged, maloriented) | mTOR pathway |
| Type IIb | Dysmorphic neurons + balloon cells (large, glassy eosinophilic cytoplasm) | “Transmantle sign”; like a forme fruste of TS |
| Type III | Dyslamination adjacent to another lesion (hippocampal sclerosis, tumor, vascular) | Dual pathology |
Malformations of Cortical Development
| Malformation | Defect stage | Pathology |
|---|
| Lissencephaly (agyria/pachygyria) | Migration | Smooth brain; thick 4-layered cortex (LIS1, DCX) |
| Heterotopia | Migration | Neurons arrested in wrong place — periventricular nodular or band (“double cortex”) |
| Polymicrogyria | Organization | Too many small fused gyri; abnormal lamination |
| Schizencephaly | Migration/cleft | Grey-matter-lined cleft (pia-to-ventricle) |
| Hemimegalencephaly | Proliferation | Enlarged dysplastic hemisphere; mTOR/somatic mosaic |
Neurocutaneous Substrates & Rasmussen
| Entity | Pathology | Signature |
|---|
| Tuberous sclerosis | Cortical tubers (balloon cells + dysmorphic neurons), subependymal nodules, SEGA | TSC1/TSC2 → mTOR; “candle-guttering” nodules |
| Sturge-Weber | Leptomeningeal capillary-venous angiomatosis; cortical calcification & atrophy beneath | GNAQ; “tram-track” gyriform calcification |
| Rasmussen encephalitis | Unihemispheric chronic T-cell encephalitis; microglial nodules, neuronophagia, gliosis | Progressive hemiatrophy + EPC |
Neural-Tube & Posterior-Fossa Malformations
| Malformation | Pathology |
|---|
| Anencephaly | Failed anterior neuropore closure; absent calvaria/forebrain (area cerebrovasculosa) |
| Spina bifida / myelomeningocele | Failed posterior neuropore closure; open neural placode |
| Chiari II | Small posterior fossa; cerebellar vermis + medulla herniation; near-universal myelomeningocele + hydrocephalus |
| Chiari I | Cerebellar tonsils >5 mm below foramen magnum; ± syringomyelia |
| Dandy-Walker | Vermian hypoplasia + cystic 4th-ventricle dilation + enlarged posterior fossa |
| Holoprosencephaly | Failed forebrain cleavage (single ventricle); midline facial defects (SHH) |
| Finding | Diagnosis |
|---|
| CA1 + CA4 loss, CA2 spared | Hippocampal sclerosis (MTLE) |
| Balloon cells + dysmorphic neurons | FCD IIb / cortical tuber |
| Band heterotopia (“double cortex”) | DCX migration defect |
| Tram-track cortical calcification | Sturge-Weber |
| Unihemispheric T-cell encephalitis | Rasmussen |
| Single ventricle + midline face defect | Holoprosencephaly |
References
- Blümcke I, et al. ILAE classification of FCD / hippocampal sclerosis. Epilepsia. 2011–2013.
- Love S, et al. Greenfield's Neuropathology. 9th ed. 2015.
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