Epilepsy

Anatomy

100

This structure provides the majority of cholinergic innervation for the entire cerebral cortex.

What is the nucleus basalis?

200

This structure is involved in the reward/pleasure pathway and receiving input from the ventral tegmentum, amygdala and prefrontal cortex and projecting to basal ganglia

What is the nucleus accumbens?

300

These pathways project from the entorhinal cortex to the dentate gyrus granule cells and the hippocampal pyramidal cells respectively.

What are the perforant pathway and the alvear pathway?

400

Describe the phenomenon found in the perforant pathway-granule cell, mossy fiber-CA3, and Schaffer collateral-CA1 pyramidal connections that is thought to play an important role in memory formation.

What is long-term potentiation? High frequency activity at any of these synapses causes a long-lasting increase in synaptic strength between the involved neurons. The perforant pathway synapses require simultaneous pre and postsynaptic activity for LTP to be elicited suggesting an associative function.

500

Name the two major efferent subcortical pathways from the amygdala to the hypothalamus and septal area/nuclei.

What are the stria terminalis and the ventral amydalofugal pathway? Stria terminalis- C-shaped structure that runs from the amygdala to the hypothalamus and septal area (fornix of the amygdala)-one connection may carry olfactory information that either increases or decreases appetite. Ventral amygdalofugal pathway projects from the amygdala to the forebrain and brainstem; projections to the forebrain involved in emotion, motivation and cognitive functions; also carry bidirectional signals involved in homeostatic (autonomic and neuroendocrine) function and behavioral arousal between amygdala and the hypothalamus.

Where's the Focus

100

Aura with a deja-vu sensation +/- palpitation and gooseflesh, lipsmacking, L arm dystonic posturing with R hand fumbling and versive head turn to the L without post-ictal aphasia.

Mesial R temporal lobe.

200

Aura of R arm paresthesias with seizure onset revealing an asymmetrical tonic posturing with R arm extension and L arm flexion with preservation of consciousness, typically of short duration and often occurring out of sleep.

L frontal (supplementary motor cortex).

300

Preceded by sensory abnormalities beginning in the R fingertips moving/marching up the R arm followed by tonic posturing of the R arm/leg with eye deviation to the R, followed by R-sided ictal paralysis.

R parietal lobe-superior parietal foci.

400

Aura with flashing geometrical lights in the R hemi-field, ictal blinking, nystagmoid eye movements with versive head and eye deviation to the R, followed by generalized tonic-clonic semiology.

L occipital lobe with secondary generalization.

500

Aura with noted laryngeal discomfort followed by a sensation in the chest or abdomen, shortness of breath and perioral paresthesias. Seizure starts with noted dysarthria/dysphonia evolving to complete muteness may progress to tonic facial spasm or even generalized dystonia, noted hypersalivation.

Insular cortex.

Myoclonic Epilepsies

100

Due to a mutation on chromosome 6p in the Cystatin B gene on chromosome 21. Typically presents between 6 and 18 years of age with stimulus-sensitive myoclonic jerks-typically in the a.m. Intellect remain intact with late cerebellar deterioration. Somatosensory evoked potentials may be high in amplitude. Diagnosis with skin biopsy from axillary region-revealing membrane-bound vacuoles in eccrine sweat glands.

Unverricht-Lundborg Disease.

200

Due to a defect in the gene encoding a tyrosine phosphatase, biopsies of various tissues reveals intracellular polyglucosan containing inclusions in the skin, muscle, liver and brain. Typically begins between 6-19 years of age, initial seizures are GTC or myoclonic, may have simple partial visual seizures. Condition is progressive with increasingly severe myoclonus, ataxia and dementia.

Lafora Body Disease.

300

Maternally inherited mitochondrial mutation, variable age of onset. Myoclonus, tonic-clonus seizures and ataxia in addition to signs of mitochonidrial disease i.e. deafness, myopathy, optic atrophy or lipomas. Diagnosed with muscle biopsy.

MERRF (Myoclonic Epilepsy with Ragged Red Fibers).

400

Autosomal recessive lysosomal storage disorder characterized by accumulation of abnormal amounts of lipopigment. Characterized by progressive loss of vision, seizures (GTC and myoclonic) and cognitive decline. Electron microscopy on skin, rectal, or conjunctival tissue may show osmophilic depositis, curvilinear bodies, fingerprint profiles or rectilinear complexes. Also an infantile form that is due to a defect in the CLN1 gene at 1p (microcephaly, epilepsy and regression.

Neuronal Ceroid Lipofuscinoses.

500

Due to a defect in neuraminidase-cleaves sialic acid from galactose. Referred to as cherry-red spot myoclonus syndrome. Typically present with gait disturbance and loss of visual acuity, myoclonus, ataxia, leg tremors and seizures. Myoclonus worsens over time, little cognitive deficits nor change in life expectancy. Diagnosis assisted with elevated sialyligosaccharides in urine.

Sialidosis Type 1.

Anti-seizure Medications

100

Name two medications whose mechanism of action is sodium channel blockade?

Carbamazapine, Phenytoin.

200

Which anti-epileptic binds to synaptic vesicle protein (SV2A), may block N-type calcium channel and inhibit delayed rectifier K+ current

Levitiracetam.

300

Which GABA receptor do both barbituates and benzodiazepines work on and how?

GABA A. Benzodiazepines increase the frequency of opening of the GABA channel. Barbituates increase the duration of time that the channel is open.

400

Name four highly protein bound anti-seizure medications. Why is that important?

Lipid solubility and protein binding determine the CNS availability and is responsible for many drug-drug interactions/levels between AEDs i.e. phenytoin and valproic acid.

500

Discuss the most common/most important side effects of the following medications: carbamazepine, lamotrigine, phenytoin, topiramate, and valproate.

Carbamazepine- hyponatremia, agranulocytosis, liver inducer, autoinduction. Lamotrigine: SJS. Phenytoin-gum hyperplasia, hypertrichosis, non-linear kinetics, lupus-like syndrome, cerebellar atrophy, coarsening of facial features; IV form can cause arrhythmias and purple glove syndromes. Topiramate-kidney stones, weight loss, metabolic acidosis, word-finding difficulties. Valproate- hepatotoxicity, weight gain, POS, alopecia, pancreatitis, tremor, hyperammonemia; increased risk for liver failure if under two years.

Epileptic Syndromes of Childhood

100

Occurs in ages 4-12, presents with nocturnal generalized tonic-clonic seizures; may also have simple partial seizures with motor symptoms involving the face often occurring during sleep or upon awakening. The EEG shows centro-temporal spikes seen bilaterally increasing during sleep.

Benign Rolandic Epilepsy of Childhood.

200

Occurs between 3-10 years of age, triad of several seizure types including generalized tonic, generalized atonic, and atypical absence seizures, a characteristic interictal EEG of abnormality of generalized slow and spike and wave discharges (<2.5 Hz) in waking and bursts of paroxysmal fast activity (~10 Hz) in sleep.

Lennox-Gastaut Syndrome.

300

Occur ages 1-14 peaking 4-5 years, seizures include autonomic manifestations, particularly ictal vomiting, altered responsiveness and arrest of activity, and deviation of eyes. Seizures can be prolonged lasting longer than 30 minutes and predominate during sleep. The EEG shows multifocal spikes with posterior predominance.

Panayiotopoulos Syndrome.

400

Occurs between 2-8 years with cognitive decline most common initial manifestation being verbal auditory agnosia associated with an EEG pattern of continuous spike-and-wave activity during slow wave sleep.

Landau Kleffner syndrome.

500

Occur between 1-14 years of age often presenting with focal-onset motor seizures and progressing to more frequent episodes or evolving to complex partial or secondary generalized tonic-clonic seizures. Progressive hemiparesis and other deficits occur with general intellectual decline. Imaging shows progressive hemiatrophy . In some patients an autoimmune etiology is suspected with antibodies to the GluR3 subunit of the glutamate receptor. Treated with IVIG, PX but hemispherectomy is generally required to achieve seizure control.

Rasmussen Syndrome.