Epilepsy and Multiple Sclerosis Flashcards
What is a seizure and what is epilepsy?
A seizure is transient dysfunction of all or part of the brain due to excessive discharge of a group of neuron causing sudden and transient symptoms of a motor, sensory, autonomic, or psychic nature. Seizures can be provoked or unprovoked.
Recurrent unprovoked seizures is epilepsy.
Describe the incidence of epilepsy.
Incidence: peaks in early childhood and the elderly.
Prevalence: between 2.5 and 3% of the population has two or more seizures during their life.
Describe the symmetry that should (or shouldn’t) be seen on an EEG. What does an EEG measure?
The front of the brain should look different from the back but the left should look the same as the right. An EEG is a measure of extracellular current from the summed activity of many neurons. It mainly reflects summed excitatory and inhibitory input to pyramidal neurons.
Describe the categories of ILAE classification of seizures.
- Mode of seizure onset: generalized, focal, unknown
- Epilepsy syndromes: organized by age and onset, most epilepsy cannot be classified this way
- Epilepsy etiology: genetic, structural or metabolic, unknown
- Evolution of time: self limited or not, responsive to treatment or not
Describe the types of seizure onset and how they spread.
Generalized seizures start deep in the center of the brain and spread to both sides. They can include cortical and subcortical structure but need not include the entire cortex. Both sides of the body do the same thing.
- Absence: sudden arrest of activity, staring, unresponsiveness, eye flutter
- Myoclonic: quick, symmetric muscle jerks
- Tonic-clonic: grand mal seizure, generalized convulsion beginning with bilateral extension, stiffening, and then rhythmic shaking
- Tonic: bilateral extension
- Clonic: rhythmic shaking
- Atonic: sudden loss of neck and trunk tone (falling)
Focal seizures can be with or without impairment of awareness and can evolve to bilateral convulsive seizure. They have different activity on the left and right side of the brain on an EEG.
Describe the appearance of focal seizures in different parts of the brain.
Frontal lobe onset:
- Motor strip: clonic shaking of contralateral limb
- Anterior to motor strip near midline: complex, bilateral, hyperactive motor activity that is not rhythmic
- Broca’s area: expressive language dysfunction
- Fronto-polar: arrest of activity, hypomotor
Temporal lobe onset: aura, arrest of activity, unresponsiveness, motor automatisms (useless reptitive motor activity that isn’t clonic)
Parietal lobe onset: sensory signs or signs based on propagation to other lobes, often clinically silent
Occipital lobe onset: visual signs may be present, propagates to temporal lobe, often clinically silent
Describe the various etiologies of epilepsy.
- Genetic: presumed or proven
- Structural/metabolic: can be acquired (stroke, trauma, infection, tumor) or developmental (cortical malformations)
- Unknown
The age of onset typically correlates with different etiologies.
Why is it important to decide if a seizure is focal or generalized?
Different drugs are used to treat each. About 60% of epilepsy is treatment response and some children can outgrow their seizures, perhaps due to changes in gene expression.
What kinds of acute pathologies can provoke a seizure? What kinds of chronic pathologies cause seizures?
Acute: infection, metabolic, drugs, alcohol, trauma, stroke, tumor, subdural hematoma, arteriovenous malformation, hemorrhage
Chornic: tumor, malformations of cortical development, mesial temporal sclerosis, genetic factors
Structural lesions or alterations to normal circuitry can cause seizures. What functional changes, acquired or developmental, cause seizures?
Acquired: drugs, metabolic, toxins
Developmental: channelopathies or synaptic alterations
What is the general principle behind epilepsy?
There is an imbalance between excitation and inhibition such that excitatory conditions predominate
- Excitation: mossy fiber sprouting, changes in EAA receptors, presynaptic changes
- Inhibition: GABA receptor change, loss of interneurons, change of interneuron activity
What is epileptogenesis?
The general process occurring in the brain before a patient develops spontaneous seizures after an insult. Acute damage leads to progressive damage which leads to hyperexcitability and seizures. Seizures lead to more progressive damage.
What is the relevance of the cortical network in epilepsy?
There is an excitatory center with an inhibitory surround and if the inhibitory surround is interrupted, the excitatory potential can spread and cause epileptiform activity. Depending on where this activity occurs, the symptoms differ.
What are the two mechanisms for focal seizures?
Paroxysmal depolarization shift: prolonged calcium depolarization leads to sodium mediated action potentials. Prominent after hyperpolarization is due to opening of calcium dependent potassium channels. This is the hallmark of partial onset seizures and is the cellular correlate of the focal interictal epileptiform spike–this is the “functional unit” of a seizure.
Sustained repetitive firing: mediated by voltage gated sodium channels is the mechanism of seizure generation. Does not require inward calcium current.
Describe the genetic mechanism for generalized seizures.
The mechanism for generalized seizures involves thalamo-cortical projections, specifically from intralaminar nuclei which have diffuse cortical connections and are capable of synchronizing cortical activity. Specifically, T-type calcium channels are responsible for burst synchronization and alterations in this system may cause some genetic forms of epilepsy.
Describe the presentation of MS.
85% of patients present with relapsing remitting MS, 15% are primary progressive or progressive relapsing MS. Secondary progressive acts like relapsing remitting but turns into progressive.
- Focal weakness: UMN monoparesis, hemiparesis, or paraparesis
- Focal numbness or paresthesias in bands
- Optic neuritis
- Speech difficulties (dysarthria/slurring)
- Lhermitte’s: flexion of neck which causes paresthesias
- Uhthoff’s: symptoms exacerbated by overheating
- Dyscoordination
- Urinary symptoms: spasticity, frequency
- Spasticity: often in legs
Describe the natural history of MS.
After about 15 years, 50% of untreated patients need ambulatory aid. The majority of patients do not end up in a wheelchair and nearly all patients accept treatment. WIthin 15 years, about 50% of RRMS convert to progressive MS. Treatment with interferon increases natural history by about 30%.
How is MS diagnosed? What are the characteristic radiographic findings? What other information is used to make the diagnosis? What is evident in the image below?
Radiographic findings include lesions disseminated in time and space with periventricular ovoid lesions perpendicular to the ventricles (demyelination–Dawson’s fingers) due to increased water where myelin is disrupted.
An accurate history and neurologic exam are also important tools in making the diagnosis. Useful tools include MRI, evoked potentials, and LP (multiple IgG molecules)
Image: Dawson’s fingers
