Makindo Medical Notes

Focal cortical dysplasia (FCD) is a malformation of cortical development where a localised area of cortex fails to form its normal six-layered architecture. It is one of the commonest structural causes of drug-resistant focal epilepsy in children and an important cause in adults. The lesion is typically present from birth but may only declare itself later with seizures. Surgical resection can be highly effective if the dysplastic cortex is well-localised and safely accessible. :contentReference[oaicite:1]{index=1}

Pathophysiology

• During fetal development, neuroblasts must proliferate, migrate and organise into orderly cortical layers. In FCD this process is locally disrupted, leading to abnormal lamination and sometimes abnormal neuron morphology.
• Many cases, especially type II FCD, are now linked to dysregulation of the mTOR signalling pathway (e.g. somatic variants in MTOR, DEPDC5, TSC1/2 and related genes), blurring the boundary with tuberous sclerosis and other mTORopathies. :contentReference[oaicite:2]{index=2}
• The malformed cortex is highly epileptogenic: altered synaptic connectivity, aberrant glutamatergic circuits and abnormal GABAergic inhibition lower seizure threshold and promote recurrent focal seizures.

Classification (ILAE – simplified)

The widely used ILAE / Blümcke classification divides FCD into three major groups based on histopathology, with an updated consensus published in 2022. :contentReference[oaicite:3]{index=3}

Type I – Isolated architectural abnormality

• Definition: Abnormal cortical layering (dyslamination) without dysmorphic neurons or balloon cells.
• Subtypes:
  • Ia – abnormal radial lamination
  • Ib – abnormal tangential lamination
  • Ic – combination of radial and tangential abnormalities
• Clinical: Often temporal lobe; can be subtle; seizures may start later in childhood or adult life.

Type II – Isolated architectural + cytological abnormality

• Definition: Dyslamination plus abnormal neuron morphology.
• Subtypes:
  • IIa – dysmorphic neurons
  • IIb – dysmorphic neurons plus balloon cells (large, dysplastic cells with glassy cytoplasm)
• Clinical: Often presents in early childhood with drug-resistant focal seizures; frequently frontal; strong association with mTOR pathway variants. :contentReference[oaicite:4]{index=4}

Type III – FCD associated with another principal lesion

Here the cortical dysplasia is adjacent to another epileptogenic pathology:

• IIIa – hippocampal sclerosis
• IIIb – glioneuronal tumour (e.g. DNET, ganglioglioma)
• IIIc – vascular malformation
• IIId – early life acquired lesion (e.g. perinatal stroke, trauma, infection)

In practice you are treating a dual pathology – both the FCD and the associated lesion contribute to epileptogenesis. :contentReference[oaicite:5]{index=5}

Clinical Presentation

• Epilepsy: The hallmark is focal seizures, often drug-resistant. Semiologies depend on lobe – e.g. motor seizures from frontal FCD, sensory auras from parietal lesions, déjà vu or psychic phenomena from temporal FCD.
• Age at onset: Commonly childhood or adolescence; type II lesions often present earlier and more severely than type I. :contentReference[oaicite:6]{index=6}
• Seizure pattern: Frequent focal impaired-awareness seizures, focal to bilateral tonic–clonic seizures, and in some children epileptic encephalopathy with developmental regression.
• Neurology: Many patients have a normal interictal exam; focal deficits (e.g. visual field cut, hemiparesis) suggest large or eloquent-area lesions.
• Cognition: Long-standing uncontrolled seizures, especially with early onset, can lead to global developmental delay or learning difficulties.

MRI and Other Imaging

High-quality MRI is central to FCD diagnosis. Thin-slice 3D T1, axial and coronal T2 and FLAIR are standard; many centres add dedicated epilepsy protocols. :contentReference[oaicite:7]{index=7}

Typical MRI features

• Cortical thickening in a focal region, often with abnormal sulcal/gyral pattern.
• Blurring of the grey–white junction beneath the lesion.
• T2/FLAIR hyperintensity in the underlying white matter; on T1 this area is often relatively hypointense.
• Transmantle sign: in type IIb, a funnel-shaped band of T2/FLAIR hyperintensity extending from the cortex towards the ventricle. :contentReference[oaicite:8]{index=8}
• Type I lesions may be much more subtle, sometimes just lobar/sub-lobar atrophy with mild white-matter T2/FLAIR change.

Advanced imaging

• FDG-PET: typically shows focal hypometabolism corresponding to the dysplasia and can localise MRI-negative FCD.
• MEG and functional imaging: help define the epileptogenic zone and its relationship to eloquent cortex in complex surgical candidates.
• Even with optimal MRI, some FCDs remain radiologically occult and are only discovered histologically after surgery. :contentReference[oaicite:9]{index=9}

EEG and Electroclinical Correlation

• Interictal EEG often shows focal spikes or sharp waves arising from the region of dysplasia, sometimes with a characteristic repetitive pattern.
• Ictal EEG recordings help define seizure onset and spread; this may be concordant with the MRI lesion or more widespread.
• In presurgical evaluation, many patients require video-EEG telemetry, and some need invasive monitoring (subdural grids or depth electrodes) to map the epileptogenic zone precisely. :contentReference[oaicite:10]{index=10}

Diagnosis

FCD is diagnosed by integrating:

• Clinical data – focal, often drug-resistant epilepsy; age at onset; neurodevelopmental history.
• Imaging – supportive MRI features ± PET/SPECT; sometimes lesion-negative MRI with strong electroclinical suspicion.
• EEG – demonstration of focal epileptiform activity.
• Histopathology – definitive classification when surgical tissue is available.

Management

Medical therapy

• First-line management is standard anti-seizure medication, but a large proportion of patients meet criteria for drug-resistant epilepsy after failure of two appropriate drugs.
• Drug responsiveness varies; some type I lesions may be relatively easier to control, while type II and early-onset cases are often refractory. :contentReference[oaicite:11]{index=11}

Epilepsy surgery

• For well-localised FCD not involving critical eloquent cortex, resective surgery is the most effective treatment and can achieve seizure freedom in a substantial proportion of patients.
• Outcomes are best when:
  • There is a clear MRI lesion concordant with EEG.
  • The lesion can be completely resected with acceptable functional risk.
• Type II FCD with visible lesions tends to have particularly good surgical outcomes in experienced centres. :contentReference[oaicite:12]{index=12}
• When resection is not possible, neuromodulation (VNS, DBS, RNS – where available) may be considered as palliative options.

Emerging therapies

• As mTOR pathway activation is a common mechanism, mTOR inhibitors (e.g. everolimus) are being explored in selected cases, mirroring experience in tuberous sclerosis–associated epilepsy. :contentReference[oaicite:13]{index=13}

Prognosis and Follow-up

• Without effective control, long-standing FCD-related epilepsy can lead to cumulative cognitive and psychosocial impairment.
• Successful surgery, particularly in children, can markedly improve seizure control and developmental trajectory, but some deficits (e.g. language, memory) may persist depending on lesion location and pre-existing injury.
• Patients need ongoing follow-up in a specialist epilepsy clinic for medication optimisation, neuropsychology, and psychosocial support.

Key Exam / Teaching Points

• FCD is a focal malformation of cortical development and a major cause of drug-resistant focal epilepsy in children.
• ILAE classification: Type I (architectural), Type II (dysmorphic neurons ± balloon cells), Type III (associated with another lesion).
• MRI clues: focal cortical thickening, grey–white blurring, subcortical T2/FLAIR hyperintensity, ± transmantle sign.
• Surgical resection of well-localised FCD offers the best chance of seizure freedom; multidisciplinary work-up (neuroimaging, EEG, neuropsychology) is essential.