Week 2 Day 1

Front 1

A Type of neuronal storage disease

Back 1

Gangliosidoses

Front 2

What are the triggers for seizure pathophysiology

Back 2

Genetic predisposition
Trauma, ischemia, stroke, malformation of cortical development
Febrile illness, sleep deprivation

Front 3

What are the factors involving the excitatory/inhibitory imbalance of seizures?

Back 3

GABA, K and Cl, Basal Ganglia
NMDAm AMPA; alteration of voltage gated channels
Bursting neurons

Front 4

Tendency to have recurrent, unprovoked seizures

Back 4

Epilepsy

Front 5

Idopathic seizures

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Genes are involved but not sure in what capacity

Front 6

"We have no idea" seizures

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Cryptogenic

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Symptomatic seizures examples

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Stroke, malformation

Front 8

Consciousness is not impaired in this type of seizure

Back 8

Simple partial seizure

Front 9

Simple partial seizure presentation?

Back 9

Depend on localization; can involve clonic movements of face, arm, leg

Brief; No post-ictal symptoms; Todd paralysis can occur

Front 10

Complex partial seizure presentation

Back 10

Consciousness is impaired-cannot recall; lasts 30 sec to minute
Temporal lobe seizure-->proceded by an aura (fear, stomach pain, light headedness, distortion of memory or time)
Often with Autonomic Symptoms
Automatisms: Facial grimacing, gestures, chewing, lip smacking, finger snapping, repetitive speech

Post-ictal impairment=lethargy, confusion

Front 11

Frontal Lobe origin presentation for complex partial seizures

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Arrest of activity
Motor manifestations
Versive head/or neck movements
Blank stare
Abrupt on and off

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Tonic clonic seizure presentation

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Loss of consciousness with stiffening of limb (tonic)
Evolution to generalized jerking of muscles
Deep sleep post ictal

Focal onset
Childhood

Front 13

Blank stare seizure?

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Absence seizure; lasts 30 seconds

Front 14

Clonic seizures presentation

Back 14

Focal, multifocal; rarely ever generalized
associated with EEG change
Migrating clonus indicates metabolic or anoxic damage

In children (dont have the thalamic connections)

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Tonic Seizures presentation

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Brief, 60 seconds
Sudden onset of increased extensor tone
Impaired consciousness

Front 16

"Drop attack"
Sudden loss of tone

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Atonic seizure

Front 17

Sudden, brief (<350 mS)
Shock-like
Generalized or confined to face, trunk
Sometimes a sign of diffuse brain injury

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Myoclonic seizure

Front 18

30 minutes of sustained seizure activity

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Status Epilepticus

Front 19

For focal seizure follow up with

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MRI

Front 20

For primary generalized epilepsy follow up with?

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EEG

Front 21

What are the basic mechanism for antiseizure agents

Back 21

Changes in voltage reg ion channels that lead to excessive depolarization
Increase GABA function
Reduce excitation (block glutamate receptors)

Front 22

What is the only anti seizure drug that isnt metabolized

Back 22

Gabapentin

Front 23

Phenytoin mech of action

Back 23

Use dependent effect on sodium channels; inhibits the generation of repetitive action potentials

Front 24

Pharmacokinetics of Phenytoin

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Highly protein bound
Pharmacokinetics are dose dependent
Changes from 1st order to zero order as does is increased; often while in the therapeutic range

Front 25

Uses for Phenytoin

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Generalized tonic-clonic seizures
Partial seizures
NOT abscence

Front 26

Toxicity of Phenytoin

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Nausea
Gingival hyperplasia (not dose dependent)
Hirsuitism
Teratogenicity; fetal hydantoin syndrome; cardiac defects, cleft palate; Rash (not dose dependent)

Front 27

Carbamazepine mech of action

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Similar to phenytoin; blocks Na channels at therapeutic concentration

Front 28

Tx of Carbamazepine

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Drug of choice for partial seizures
NOT in absence

Front 29

Toxicity of Carbamazepine

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Increased risk of spinal bifida
Rare blood dyscasias

Front 30

Most common type of seizure?

Back 30

Complex partial (temporal lobe)

Front 31

Mech of action for Ethosuximide

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Reduces low-threshold T-Type Calcium currents in thalamic neurons

Front 32

Ethosuximide side effects and toxicity

Back 32

Gastric distress, and lethargy/fatigue

Front 33

First choice drug treatment of absence seizures

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Ethosuximide

Front 34

Mechanisms (3) of valproic acid

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Blocks repetitive neuronal firing
May reduce T-tuep Ca++ currents
Increases GABA concenrations

Front 35

Clinical uses of Valproic acid

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Absence seizures
Absence seizures with concomitant-generalized tonic-clonic seizures
Myoclonic seizures

Front 36

Side effects of Valproic acid

Back 36

Weight gain, hair loss
Hepatotoxicity (not dose related)
Spinal bifida (not dose related)

Front 37

NMDA antagonist (block glycine which makes Glutamates action more effective) and also potentiates GABA

Back 37

Felbamate

Front 38

use for Felbamate?

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Partial seizures that dont work with other agents

Front 39

TOXICITY of Felbamate

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aplastic anemia and hepatic failure

Front 40

Structural analog of GABA but is NOT a GABA agonist

Back 40

Gabapentin
NOT metabolized and no protein binding making it devoid of the usual drug interactions

Front 41

Tx Gabapentin

Back 41

Adjunct therapy in the treatment of partial seizures ir with secondarily generalized tonic-clonic seizures

Neuropathic pain and ALS

Front 42

More potent form of Pregabalin

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Pregabalin; may interact with alpha 2-delta subunit of voltage-gated calcium channels

Front 43

Tx pregabalin

Back 43

Adjunctive therapy for partial seizures
Management of neuropathic pain ass. with diabetic peripheral neuropathy and postherpetic neuralgia and fibromyalgia

Front 44

Lamotrigine mech of action

Back 44

Blocks repetitive action poteintials and may block Na+ channels

Front 45

Lamotrigine use

Back 45

Partial
Tonic-clonic
Absence
Bi-polar disorder

Front 46

Can cause Stevens-Johnson syndrome

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Lamotrigine

Front 47

Inhibits excitatory transmission by antagonizing the ability of excitatory amino acids to activate the kainate/AMPA subtype of glutamate receptor. May also block sodium channels similar to phenytoin.

Back 47

Topiramate
Block the spread of seizures rather than raise the seizure threshold

Front 48

Topiramate Tx

Back 48

Add-on therapy of adults with partial seizures
Also used for Migraine prevention
Can cause WEIGHT LOSS

Front 49

Inhibits the GABA transporter, GAT-1, and thus reuptake of GABA, the major inhibitory neurotransmitter in the brain. Increased GABA in synapse.

Back 49

Tiagabine

Front 50

Add on treatment for both complex and simple partial seizures

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Tiagabine
Adverse effects include dizziness, tremor and somnolence

Front 51

Tx for Levetiracetam

Back 51

Used as adjunctive therapy for partial seizures. Also indicated for adjunctive treatment of myoclonic seizures and primary generalized tonic-clonic

Front 52

Acts at both sodium and Calcium channels

Back 52

Zonisamide
Stops the spread of seizures and suppresses their focus

Also newer drug Clobazam (also suppresses neuronal hypersynchronization and inhibits carbonic anhydrase)

Front 53

SE of Zonisamide

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Ataxiam anorexia, nervousness, fatigue and speech impairment
Approved for adjunctive treatment of adults with partial seizures

Front 54

Acts by irreversible inhibiting GABA metabolism

Back 54

Vigabatrin

Front 55

Main SE for Vigabatrin

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Permanent effects on vision ("blind as a vigaBATrin)

Front 56

Tx for vigabatrin

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Adjunctive tx of complex partial seizures and infantile spasms

Front 57

Enhances slow inactivation of voltage gated sodium channels

Back 57

Approved for adjunctive tx of partial seizures

Front 58

Antiseizure drugs that can cause hepatotoxicity

Back 58

Phenytoin, carbamaxepine, valproic acid

Front 59

Antiseizure drugs that cause dermatologic effects

Back 59

Carbamazepine, lamotrigine

Front 60

Partial secondarily generalized seizure drugs?

Back 60

Carbamazepone
Gabapentin
Oxcarbaxepine
Phenytoin

Front 61

Treats all seizures except absence

Back 61

–topiramate
–zonisamide
–levetiracetam
–felbatol
–rufinamide
–lacosamide

Front 62

Treat absence seizures

Back 62

Ethosuximide, valproic acid, lamotrigine

Front 63

Medically resistant epilepsy options

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Felbatol
Ketogenic diet
Vagal nerve stimulation
Epilepsy surgery

Front 64

Genetic inheritance of most Lysosomal storage diseases

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Autosomal recessive (such as Niemann-Pick disease)

Front 65

What are the X-linked recessive inherited lysosomal storage diseases

Back 65

Fabry disease
Hunter syndrome

Front 66

Suspicions for a metabolic disorder

Back 66

Unexplained lethargy, confusion, somnolence or coma and many more signs

Check glucose, ammonia, and pH
Store a "critical sample" for hypoglycemia

Front 67

A type of neuronal storage disease

Back 67

Gangliosidoses

Front 68

Accumulation of ____ substrates/metabolites in a storage disorder

Back 68

Inert (not active!!)

Front 69

Tay Sachs disease genetics

Back 69

High incidence in Ashkenazi Jews
On Chromosome 15
Alpha gene

Front 70

Presentation of Tay-Sacs

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Normal at birth
Retardation at 6 months
CHERRY red spot in macula
Death by 2-3 years
Blindness
Flaccidity
Prominent forehead

Front 71

Genetics of Sandhoff Disease

Back 71

Chromosome 5
Beta subunit

Front 72

Microscopic findings in Tay-Sachs

Back 72

Enlarged neurons filled with PAS
Membranous cytoplasmic bodies

Front 73

Deficiency of Galactocerebroside-B-galactosidase

Back 73

Krabbe's disease
Autosomal recessive gene on Chromosome 14

Front 74

Krabbe's disease pathophys

Back 74

Globoid cell leukodystrophy
Psychosine injures the oligodendrocytes
Galactocerebroside accumulates in the Globoid cells
Both the CNS and PNS are affected

Front 75

Dx of Krabbe's disease

Back 75

Enzyme assay of WBC or cultured fibroblasts

Front 76

Clinical course and tx of Krabbe's disease

Back 76

Normal at birth
Irritability
Deterioration of motor function (tonic spasms)
Optic atrophy, blindness
CSF protein elevated

Tx: umbilical cord/bone marrow transplantation (in presymptomatic phase)

Front 77

?

Back 77

Globoid Cells (Krabbe's disease)

In EM globoid cells contain crystalloid straight or tubular profiles

Front 78

Deficiency in Aryl sulfatase A

Back 78

Metachromatic Leukodystrophy
On Chromosome 22

Front 79

Lipids (sulfatides) accumulate in brain, peripheral nerves and kidney

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Metachromatic leukodystrophy

Lipid accumulation leads to breakdown of myelin

Front 80

Clinical presentation of metachromatic leukodystrophy

Back 80

Can present in different stages of childhood (most common is late infantile)
Present with gait disorder and motor symptoms

Treat with bone marrow stem cell tranplantation

Front 81

Brain is externally normal but the white matter is very firm

Marked loss of myelin with preservation of U fibers

Back 81

Metachromatic leukodystrophy

Front 82

Acidified cresyl violet stain (brown of white matter deposits)

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Metachromatic Leukodystrophy

Front 83

Decreased activity of very long chain fatty acyl-CoA synthetase

Back 83

Adrenoleukodystrophy (schilder's disease)

Front 84

Excess of very long chain fatty acid esters in plasma, cultured fibroblasts and affected organs

Back 84

Adrenoleukodystrophy-Peroxisomal disorder-cytoplamic spherical "microbodies"
Involved in fatty acid B-oxidation

X-linked

Front 85

Onset of Adrenoleukodystrophy and presentation

Back 85

Classic form: 5-9 years or 11-21 years; dementia, visual hearing loss, seizures, adrenal insufficiency FOLLOWS Neuro signs and sx

Adrenomyeloneuropathy form: Adults (20-30 years); slowly progressive leg clumsiness/stiffness; eventual spastic paraplegia; Adrenal insufficiency precedes Neuro signs

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Gray discoloration of white matter; marked firmness

Severe demyelination with U fiber preservation

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Adrenoleukodystrophy

Front 87

******Pervascular inflammation and PAS positive macrophages

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***Adrenoleukodystrophy****

Front 88

Hepatic encephalopathy occurs d/t

Back 88

severe liver disease or chronic portocaval shunting
may be d/t hyperammonemia

Front 89

Manifestations of hepatic encephalopathy

Back 89

Early manifestations: inattentiveness and short term memory impairment

Later features: confusion, asterixis, stupor

Foul breath, hyperventilation

Front 90

MRI abnormalities of Hepatic encephalopathy

Back 90

Increased T1 signal in the globus pallidus, subthalamus and midbrain

Cortical edema

Front 91

Alzheimer Type II astrocytes

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Hepatic encephalopathy

Front 92

Hypoglycemia affects which parts of the brain?

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Changes in the temporal, occipital, and insular cortices, hipocampus, and basal ganglia, often with thalamic sparing

Front 93

Mitochondrial diseases genetics

Back 93

Shows maternal inheritance
Mitochondrial proteins are encoded wtihin the mitochondrial and nuclear genome

Front 94

Presentation of myocardial myopathy

Back 94

Progressive weakness, ataxia, hearing and vision deficit and autonomic dysfunction

MRI of brain showed a cyst and general atrophy
Decreased Cytochrome c reductase

Front 95

Heteroplasmic point mutation in mt-tRNA^leu

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MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes)

Front 96

Heteroplasmic point mutation in mt-tRNA^lys

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MERRF (myoclonic epilepsy with ragged red fibers

Front 97

–Usually caused by large single mtDNA mutation
–Causes pigmentary retinopathy and opthalmoplegia before 20 years of age

Back 97

Kears-Sayre Syndrome

Front 98

Mutation in nuclear DNA
deficiency in pathway converting pyruvate to ATP
Decreased activity of cytochrome C oxidase
recessive
Lactic acidema

Back 98

Leigh's disease (subacute necrotizing encephalopathy)

Front 99

Leigh's disease (subacute necrotizing encephalopathy)

Back 99

Arrest of development, hypotonia, seizures, extraoxular palsies

Death between 1 and 2 years

Front 100

Periventricular gray matter tissue destroyed; around cerebral aqueduct and 3rd ventricle

Back 100

Leigh's disease

Histologically has a spongiform appearance and vascular proliferation

Front 101

Wernicke encephalopathy cause and presentation

Back 101

Vitamin B1 deficiency

Ophthalmoplegia, nystagmus
Ataxia
Confusion, disorientation, eventual coma

Gray-brown discoloration with petchial hemorrhages (acutely)
Atrophy and discoloration of mamillary bodies (chronic state)

Front 102

Korsakoff Psychosis presentation

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Loss of anterograde episodic memory, confabulation

preserved intelligence and learned behavior
D/t thiamine deficiency and repeated episodes of Wernicke's
Damage to medial dorsal nucleus of thalamus

Front 103

Presentation of Vitamin B12 (cobalamin) deficiency

Back 103

Ataxia, romberg, spasticity, decreased reflexes, mental status changes

Subacute degeneration of the spinal cord
Usually d/t pernicious anemia

Anterior and lateral corticospinal tracts and posterior columns are vacuolated and demyelinated

Front 104

Back 104

Vitamin B12 deficiency

Front 105

Where does carbon monoxide bind?

Back 105

Globus pallidus (rick in iron)
binds irreversible to hemoglobin, displacing oxygen

CO poisoning usually accompanied by hypotension/ischemia

Front 106

CO poisoning presentation

Back 106

Motor, cognitive, psychiatric, and parkinsonian s/s

Front 107

Cerebellar degeneration; atrophy of the anterior superior vermis

Back 107

Chronic ethanol toxicity

Front 108

Fetal alcohol syndrome presents with?

Back 108

Growth retardation, facial deformities, cardiac defects (ASD), delayed development and mental deficiency

Small eye openings, smooth philtrum, thin upper lip

Front 109

large areas of coagulative necrosis primarily in white matter (months to years later)

Back 109

Radiation Toxicity

Also induction of neoplasms years after treatment

Front 110

Methotrexate (in combo with radiation) causes

Back 110

Disseminated necrotizing leukoencephalopathy

coagulative necrosis with axonal loss and mineralization

Front 111

Effects of Phenytoin

Back 111

Ataxia, nystagmus, slurred speech and sensory neuropathy

Atrophy of cerebellar vermis and loss of purkinje cells and granule cells

Front 112

Cocaine casues

Back 112

Seizures, strokes, hemorrhages
Infarcts/hemorrhages d/t vasospasm, emboli, hypercoaguability, hypotension