Download Neuropathology of epilepsy

Neuropathology of epilepsy
Objectives
4976
Describe pathologically several
types of congenital malformations
and acquired lesions of the
cerebral cortex that may
predispose to epilepsy.
Epilepsy: definition
An episodic disorder of the nervous
system arising from the excessively
synchronous and sustained discharge of a
group of nerve cells.
Hughlings Jackson ( 1873)
Epilepsy: definition
• Epilepsy is a disorder of the brain characterized
by an enduring predisposition to generate
epileptic seizures and by the neurobiological,
cognitive, psychological and social
consequences of this condition.
• An epileptic seizure is a transient occurrence of
signs and/or symptoms caused by the abnormal
excessive or synchronous neuronal activity in
the brain.
Wang YY et al. Brain Pathology 20:1-16, 2010
Epidemiology of Epilepsy
• Worldwide
• Rate of between 20 and 70 per 100,000
• Incidence frequently evaluated with
presumed diagnosis
• Highest in first year of life
• Commonest causes: head injury, birth
trauma, infections and cerebro-vascular
diseases
Epidemiology (2)
• 65% with a major handicapping medical
condition
• Mental retardation, seen in up to 28% of
patients, more likely in early onset cases
and with generalized seizures
• Neurologic deficits seen usually in focal
epilepsy
Epilepsy: semiology
• Petit mal: absence attacks
• Grand mal: tonic-clonic seizures
• Generalized: absence, tonic, clonic, tonicoclonic, myoclonic and atonic
• Focal or partial: simple partial, complex partial or
partial evolving to generalized seizures
Classifications
• Etiology
• Semiology
• Morphology
Morphological classification
Developmental (inherited) lesions
Acquired lesions
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Epilepsy can be focal or generalized
Neuropathology of the brain with
epilepsy: two questions
• Can the cause of the epilepsy be
identified?
• Are there any secondary lesions caused
by the epilepsy?
Epilepsy: three major categories of
problems found at examination
• 1) Malformations of cortical development
and epilepsy
• 2) Acquired lesions and epilepsy
( 1 and 2 are in line with the morphological classification
mentioned before)
• 3) Effect of epileptic seizures on the brain
Malformations of cortical
development
• Role of neuro-imaging
• Role of genetic studies in our understanding of
the etiology of these lesions
• Range is enormous, many presenting early in
life with:
- developmental delay
- encephalopathy
- congenital motor problems
- associated malformative/developmental lesions
Morphological classification of
cortical dysplasia
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Lissencephaly (agyria/pachygyria)
Polymicrogyria
Heterotopia ( laminar or nodular)
Single heterotopic white matter neurons
Focal cortical dysplasia
(Other rare forms)
Key pathogenesis of cortical
dysplasia
• Abnormality of neuronal migration: endresult of an abnormal cortical
“programming”
• Selective migrational arrest either within
the cortex or between the mantle zone and
the cortex
Focal cortical dysplasia
• Most malformation of cortical development
in surgical epilepsy series
• Type 1: Abnormal cyto-architecture
without ballooned cells or dysmorphic
neurons
• Type 2: Abnormal neurons or ballooned
cells; better results with surgery
Case history
• 21 month-old boy with a seizure disorder
• He had a medically uncontrollable partial
epilepsy with secondary generalized
• Neuro-imaging showed a focus of
increased cortical thickness and blurring of
the grey-white junction in the right
temporo-parietal area
• Scalp EEGs over this area showed
continuous spiking
Focal cortical dysplasia: etiology
• Sporadic
• Arrested neuronal migration and
differentiation
• Abnormality of progenitor cell proliferation
and programmed loss of neurons during
development
Tuberous sclerosis complex
• Most severe expression of focal dysplasia
type 2 with the presence of dysmorphic
neurons and ballooned cells
• Hemi-megalencephaly
Case History
• 4 year-old boy with mental retardation and
seizure. Investigation lead to a diagnosis of
tuberous sclerosis
• Neuro-imaging showed a few
cortical/subcortical lesions, frequently with
calcifications and subependymal nodules,
equally frequently calcified
• Decision was made to remove a larger lesion felt
to be responsible for the uncontrollable epilepsy
Mild malformation of cortical
development
• Subtle cortical abnormalities
• Neuro-imaging generally negative
Generalized malformation of
cortical development
• Lissencephaly (agyria-pachygyria)
• Polymicrogyria
• Heterotopia, laminar or nodular
Acquired epilepsies
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Tumours
Trauma
Vascular: cerebral palsy, ischemia,stroke
Infections
Fever, dehydration
Vascular malformations
Rasmussen’s encephalitis
Neurodegeneration, including Alzheimer’s
disease
Tumors and epilepsy
• Frequent cause, around 35%
• Slow growing lesions are more likely to be
associated with seizures: 70.9% of
oligodendrogliomas, 58.5% of
astrocytomas, 36.9% of meningiomas and
28.9% of glioblastomas
• Frequently the first and only sign
Effects of seizures on the brain
• Evidence that prolonged seizures and status
epilepticus can result in neuronal loss is firmly
established
• Effect of recurrent short self terminating seizures
is less clear. Experimentally, demonstration of
increased apoptosis in hippocampi; in human,
serial MRI demonstrate evidence of
hippocampal atrophy in some patients
• Childhood epilepsy carries significant risks for a
variety of cognitive and behavioral problems
Status epilepticus
• Seizure activity, continuous or intermittent
but without intervening recovery, lasting a
prolonged period:
– 60 min. for adults
– 30 min. for children
If generalized, this is a medical emergency
Status epilepticus
• More severe damage
• If prolonged with significant abnormalities
of cardio-respiratory function:
- infarcts
- death
Pathology of seizure-related
lesions
• Neuronal cell death: apoptosis or acute
damage (necrosis), leading to neuronal
loss
• Key structures are essentially the same as
the ones involved in ischemia and early
infarcts
Hippocampal sclerosis
(mesial temporal sclerosis)
• Atrophy of the hippocampus
• Strong association with drug resistant
mesial temporal lobe epilepsy
• Surgical indication in carefully selected
patients
• Considered to be acquired but unknown
etiology (link to effect of seizures on
neurons)
SUDEP
• Sudden unexpected death in epilepsy
• Occurs in up to 10% of patients
• Major causes of death in patients between
20 and 40 years
• ? Cardiac arrhythmia or respiratory failure
• Pulmonary edema at autopsy, likely of
neurogenic origin