Cortical Dysplasia: Diagnosis and Treatment
Immediate Clinical Action
Patients with cortical dysplasia and drug-resistant epilepsy should be referred for presurgical evaluation after failure of only two antiepileptic drug trials, as surgical resection offers the best chance for seizure freedom and improved quality of life. 1
Understanding Cortical Dysplasia
Definition and Clinical Impact
Cortical dysplasia represents a malformation of cortical development where the cerebral cortex forms abnormally in utero, characterized by disorganized brain cell layers, abnormally shaped neurons (dysmorphic neurons), and sometimes unusual large "balloon cells." 2
These malformations cause substantial lifelong burden including drug-resistant epilepsy (40-50% of pediatric surgical epilepsy cases), cerebral palsy, feeding difficulties, intellectual disability, and other neurological and behavioral anomalies. 1, 3
Focal cortical dysplasia (FCD) is the most common developmental malformation causing refractory epilepsy in children and the second or third most common cause in adults. 4
Diagnostic Approach
Neuroimaging Protocol
High-quality brain MRI with age-specific protocols is the cornerstone of diagnosis and must be performed by radiologists with substantial expertise in pattern recognition. 1
MRI Findings to Identify:
- Focal cortical thickening or thinning in the affected region 4
- Blurred gray-white matter junction (loss of normal boundary definition) 2, 4
- Increased T2/FLAIR signal in gray matter and subcortical white matter, often tapering toward the ventricle (transmantle sign) 4
- Focal brain atrophy in the dysplastic area 4
Critical Diagnostic Caveat:
- Type I FCD is frequently MRI-negative or shows only subtle changes that even experienced radiologists may miss, while Type II FCD is usually easier to detect on imaging. 2, 4
- The lesion visible on MRI may be smaller than the actual seizure-generating region, requiring additional functional imaging. 4
Classification System (International League Against Epilepsy)
Type I FCD:
- Subtle changes in brain cell organization 2
- Often affects temporal lobe 4
- Harder to visualize on MRI 2
- Later seizure onset, more common in adults 4
- Poorer surgical outcomes due to difficulty defining lesion boundaries 5
Type II FCD:
- More obvious abnormalities with dysmorphic neurons and balloon cells 2
- Easier to detect on MRI 2
- More extensive changes outside temporal lobe, predilection for frontal lobes 4
- Earlier onset, more severe symptoms, typically in children 4
- Better surgical outcomes when completely resected 2
Type III FCD:
- FCD combined with another brain lesion (hippocampal sclerosis, tumor, vascular malformation, or acquired pathology) in the same area 2
Functional Imaging When MRI is Negative or Equivocal
When MRI fails to show abnormalities in suspected FCD, proceed with functional neuroimaging to localize the epileptogenic zone: 4, 5
- FDG-PET to identify areas of hypometabolism 4, 5
- Ictal SPECT to capture seizure-related perfusion changes 4
- Magnetoencephalography (MEG) for seizure source localization 4
- Diffusion tensor imaging (DTI) to assess white matter tract abnormalities 4
Genetic Testing Workflow
Next-generation sequencing should be pursued to maximize diagnostic yield and enable personalized counseling on prognosis and recurrence risk: 1
- Gene panel testing targeting MCD-related genes as first-line approach 1
- Exome sequencing when gene panel is negative 1
- Genome sequencing in select cases 1
Treatment Strategy
Medical Management Reality
Antiepileptic drug treatment is consistently poor for FCD-related epilepsy, with the majority of patients remaining drug-resistant. 5, 6
- No specific drug treatment exists for FCD; any antiepileptic drug used for focal epilepsy may be tried. 6
- Design sequential AED therapy individually, considering side effects and developmental progress. 6
- Do not delay surgical evaluation while pursuing multiple failed medication trials. 1
Surgical Treatment: The Definitive Approach
Complete resection of the epileptogenic zone is required for seizure-free life, with 50-65% of FCD patients achieving seizure freedom after surgery. 5, 6
Surgical Candidacy Criteria:
- Initiate presurgical evaluation after failure of only two AED trials (not the traditional multiple failed medications). 6
- Seizure onset within first years of life with cognitive impairment warrants earlier surgical consideration due to developmental impact. 6
- Even lesions involving eloquent cortex (motor/sensory areas) may be resectable depending on preoperative neurologic status. 7
Critical Surgical Success Factors:
- Incomplete resection is consistently the strongest predictor of poor surgical outcome. 5
- Complete removal is often difficult because dysplastic tissue extends beyond what is visible on MRI. 5
- Intracranial electrode monitoring is frequently necessary for successful surgery, particularly in Type I FCD where lesion demarcation is poor. 5
- Patients with MRI-visible FCD have worse surgical outcomes compared to other focal lesional epilepsies, emphasizing the need for meticulous presurgical planning. 5
Special Consideration for Bilateral Perisylvian Polymicrogyria:
- Some patients develop secondary generalized electrographic abnormalities and drop attacks in early childhood that spontaneously improve toward the end of the first decade. 7
- Corpus callosotomy should be considered with extreme caution in these patients. 7
Prognostic Factors
Age and Developmental Impact
- Epilepsy typically manifests within the first years of life but has been documented up to age 60 years. 6
- Early seizure onset commonly accompanies cognitive impairment. 6
- Delaying surgery in young children with FCD risks irreversible developmental impairment beyond seizure control issues. 6
Intrinsic Epileptogenicity
- FCD tissue is intrinsically epileptogenic due to aberrant neural networks highly susceptible to abnormal excitation. 5
- Upregulation of drug transporter proteins has been found in FCD tissue, potentially explaining medication resistance. 6
- The dysplastic cortex shows widespread molecular disruption with both neurodevelopmental abnormalities and possible premature neurodegeneration. 8
Common Pitfalls to Avoid
- Do not accept a "normal" MRI as excluding FCD—Type I FCD is frequently MRI-negative; pursue functional imaging. 2, 4
- Do not continue prolonged medical management in drug-resistant cases—refer for surgical evaluation after two failed AED trials. 6
- Do not assume the MRI-visible lesion represents the entire epileptogenic zone—intracranial monitoring may be essential. 4, 5
- Do not perform incomplete resections—this is the primary cause of surgical failure. 5