Exam 2

Question 1

Myths surrounding suicide

Answer 1

1.) Suicidal individuals won’t tell you the truth
2.) You might give people ideas by talking about it
3.) You might offend someone by asking about it

Question 2

What percent of people saw their healthcare team in the month before they committed suicide?

Answer 2

• 45% saw their PCP
• 20% saw a mental health professional

Question 3

How to describe suicidal thoughts:

Answer 3

– passive vs active
– PQRST
– Planning/preparation: do you have a plan? specifics?
– Risk factors: why haven’t you harmed yourself? impact on others?
– Protective factors: biggest reason for living? social/pets/etc

Question 4

Non-suicidal self-injury increased risk of suicide attempt by:

Answer 4

• 3.5x
• attempt to handle intense emotions

Question 5

How to approach a pt with suicidal thoughts/SI?

Answer 5

1.) set the stage: I am going to ask you serious questions
2.) Be specific
3.) Broad questions–> specific, about plans/thoughts

Question 6

Oppositional Defiant Disorder:

Answer 6

• 10% lifetime prevalence
• a pattern of angry/irritable mood, argumentative/defiant behavior, or vindictiveness lasting at least 6 months and has at least 4 symptoms from these categories (loses temper, easily annoyed, touchy, deliberately annoying, defiant, etc)

Question 7

Conduct Disorder

Answer 7

• 3% lifetime prevalence
• a repetitive and persistent pattern of behavior in which the basic rights of other or major age-appropriate societal norms are violated.
• 3/15 symptoms required in the past 12 months, with at least one present for the past 6 months from categories: aggression to people and animals, destruction of property, serious violation of rules, and deceitfulness or theft (initiates fights, threatens others, physically cruel to people/animals, stolen while confronting another-robbing, forced SA)
• the disturbance in behavior causing clinically significant impairment in social, academic, or occupational functioning

Question 8

Antisocial personality disorder

Answer 8

• 1-4% lifetime prevalence
• disregard for and violation of others’ rights since age 15, as indicated by one of the 7 sub-features.
• person is at least 18 years of age, they had conduct disorder before ASPD, and the antisocial behavior does not occur in the context of schizophrenia or bipolar disorder

Question 9

ODD and comorbidity

Answer 9

• 92.4% of those with ODD meet criteria for at least one other disorder ( impulse-control disorders > anxiety disorders > substance use disorder > mood disorders > PTSD)

Question 10

Hispanic and black youth:

Answer 10

• are 2x more likely to be diagnosed with ODD or CD
• and are diagnosed at 40% the rate of non-hispanic white youth for ADHD

Question 11

Krabbe disease

Answer 11

– genetic, autosomal dominant
– early onset, progressive diffuse symptoms
– Demyelination Cx, brainstem, cerebellum
– Loss of GALC, accumulation of psychosine, Globoid cells
– treatment is symptomatic

Question 12

MLD: Metachromatic leukodystrophy

Answer 12

– Genetic, autosomal dominant
– Children-adult onset, seizures, cognitive and movement disorders, pain, blindness
– Central demyelination, radiating stripes in MRI
– Loss of ARSA, accumulation of sphingolipids, metachromatic deposits
– treatment is symptomatic

Question 13

MCL: Metachromatic leukodystrophy

Answer 13

– autosomal recessive, ARSA gene
– lysosomal enzyme causing mutant accumulates of sulfatides (sphingolipids)
– penetrance correlates with amount of residual ASA activity and symptoms

Question 14

ALD: Adrenoleukodystrophy

Answer 14

– Genetic, X-linked
– Different presentations: adrenal dysfxn> adult onset AMN>childhood onset cerebral demyelination
– Central brain or spinal cord inflammation and degeneration
– Loss of ALDP (ABCD1 encoded), accumulation of VLCFA>systemic inflammation
– Treatment is stem cell transplant, or Lorenzo’s oil (helps in younger pts)

Question 15

Cerebral demyelinating ALD

Answer 15

– most common in 4-10 year olds
– inflammation destroys myelin
– healthy boys (most common) start to regress: deaf/blind, seizures, loss of muscle control, progressive dementia
– death or permanent disability 2-5 years post diagnosis
– ABCD1

Question 16

AMN: Adrenomyeloneuropathy

Answer 16

– Mostly males, develop myelopathy in 20-50s
– early symptoms: incontinence–> brisk reflexes with + babinski, dorsal column dysfxn
– mental/physical deterioration–> vegetative state or death > 5 years
– In women in can present in 50s, slower progression

Question 17

Lorenzo’s oil

Answer 17

oral mix, Oleic acid (C18:1), erucic acid (C22:1), normalizes plasma (C26:0)
– does not affect C26:0 in nervous system
– not clear if it helps most pts, may help pre-symptomatic kids with ALD

Question 18

ADEM: Acute disseminated encephalomyelitis

Answer 18

– Post-infectious
– diffuse headache, lethargy, coma
– perivenous demyelination, hyperintense lesions in T2/FLAIR
– Macrophage infiltration, attack on myelin
– treatment is high dose steroids

Question 19

AHL: Acute hemorrhagic leukoencephalitis

Answer 19

– Post-infectious
– irritability, difficulty walking, impaired consciousness, typically lethal
– Large hemorrhages, MRI: large areas of inflammation
– Destruction of brain capillaries, disseminated necrosis, high neutrophils
– treatment is high dose steroids

Question 20

PML: Progressive multifocal leukoencephalopathy

Answer 20

– idiopathic
– acute diffuse neuro perturbations, confusion, headache, MCI, permanent sequelae
– Multiple lesions in T2/FLAIR
– Caused by JC virus in weakened immune systems
– Treatment is anti-retrovirals, remove meds

Question 21

Osmotic demyelination syndrome

Answer 21

– Low Na+ (hyponatremia) correction
– Diffuse, motor/sensory symptoms, lethargy, EtOH Hx, low Na+, could become locked-in
– Lesion in pons and sometimes in thalamus
– Demyelinating path in pons
– treatment is steroids, and prevention with careful Na+ correction

Question 22

Neuromyelitis optica

Answer 22

–Idiopathic
– Vision problems + transverse myelitis
– Optic nerve and spinal cord inflammation
– Anti-AQ4, anti-MOG
- treatment is steroids

Question 23

Transverse myelitis

Answer 23

– Idiopathic, symptom
– pain, weakness, paralysis, sensory problems, autonomic dysfunction
– spinal cord inflammation
– associated with post-infectious and autoimmune disorders
– treatment is steroids

Question 24

Segmental demyelination

Answer 24

– dysfunction of Schwann cells or damage to myelin sheath
– Damaged myelin engulfed by Schwann cell and macrophages
– Higher regeneration capacity in PNS
– Chronic demyelination –> axonal injury –> muscle atrophy

Question 25

Axonal degeneration

Answer 25

-- Focal event along the nerve, trauma or ischemia -- Generalized effect on neuronal cell body (neuropathy) or axon (axonopathy) -- stump undergoes regeneration following acute injury -- Chronic: muscle fibers lose neural input (denervation atrophy)

Question 26

Wallerian degeneration

Answer 26

Axon breaks down --> schwann cells catabolize myelin --> schwann cells engulf axon fragments --> recruits macrophages

Question 27

Guillian-Barre syndrome

Answer 27

-- Guillain-Barré syndrome (GBS) is an acute postinfectious polyneuropathy characterized by symmetric and ascending flaccid paralysis. In affected patients, cross‑reactive autoantibodies attack the host's own axonal antigens, resulting in inflammatory and demyelinating polyneuropathy. -- 2/3 cases are preceded by acute GI or respiratory infections post-recovery -- Infectious agents: Campylobacter jejuni, CMV, EBV, mycoplasma pneumoniae, H. influenza

Question 28

Clinical findings of Guillian-Barre

Answer 28

-- deep tendon reflexes disappear early -- symmetric, ascending paralysis with loss of sensation -- CN involvement, sensory signs, ataxia, autonomic dysfunction -- CSF: high protein with no lymphocytes, albumin-cytologic dissociation -- treatment: steroids, plasmapheresis, IV-immunoglobins

Question 29

Guillian-Barre nerve inflammation

Answer 29

-- Chronic inflammation within nerve: macrophage infiltration -- Perivenular inflammation: macrophages — attacks myelin and axons

Question 30

Leprosy:

Answer 30

-- Slowly progressive infecion of skin and nerves--> My. leprae -- Schwann cells invaded by my. leprae --> proliferate and invade other cells --> segmental demyelination and remyelination --> loss of both myelinated and demyelinated fibers --> symmetric neuropathy involving pain fibers --> loss of sensation --> injury (traumatic ulcers in extremities)

Question 31

Tuberoid Leprosy

Answer 31

-- less severe, localized, dry, scaly, skin lesions -- active cell-mediated immune response to my. leprae causes the symptoms -- nodular inflammation in the dermis that injures nerve in the vicinity

Question 32

Charcot Marie Tooth disease

Answer 32

-- Slowly progressive atrophy of calf/distal weakness -- high arches, hammer toes, muscle atrophy -- hereditary neuromuscular disorder, congenital or progressive, late onset -- Types CMT1-4, genetically heterogenous, all affect schwann cells -- Duplications of PMP22 in 70% of all cases

Question 33

Charcot Marie Tooth type 1

Answer 33

-- dominant, demyelinating motor and sensory neuropathies -- most patients retain mobility for life, but in severe cases become wheel-chair dependent -- sensory nervous system: decreased reflexes, loss of vibration sensation, painful neuropathy -- diagnosed by nerve conduction velocity

Question 34

Histopathology of CMT

Answer 34

- repetitive demyelination and remyelination causing onion bulbs -- hyperplasia surrounding individual axons --> enlargement of peripheral nerve: hypertrophic neuropathy

Question 35

Diabetic neuropathy

Answer 35

leading cause of polyneuropathy. Thickening of small blood vessels that feed distal neurons --> hypoxia --> degeneration (circulatory system issue)

Question 36

Renal failure neuropathy

Answer 36

distal neuropathy, symmetric, happens in recovery following dialysis

Question 37

Other neuropathies

Answer 37

1.) Chronic liver disease, chronic respiratory insufficiency, thyroid dysfunction, vitamin B deficiencies 2.) Exposures: chemicals, alcohol, chemotherapy 3.) Heavy metals: lead, mercury, arsenic

Question 38

Traumatic neuropathies

Answer 38

-- most common form affecting a single nerve -- Lacerations, avulsions, direct severance --> tangle from regrowth --> traumatic neuromma -- compression neuropathy: carpal tunnel syndrome

Question 39

Neuropathy caused by malignancy

Answer 39

1.) PNS tumors: schwannoma, neurofibroma, malignant peripheral nerve sheath tumor 2.) Brachial plexopathy: from neoplasms of apex of the lung 3.) Obturator palsy: pelvic neoplasms 4.) CN palsies: intracranial tumors or at the base of the skull 5.) Paraneoplastic syndrome: cancer-fighting immune cells --> diffuse symmetric polyneuropathy 6.) Chemotherapeutic agents as toxins

Question 40

Drugs to reduce intracranial pressure

Answer 40

1.) acetazolamide 2.) Furosemide 3.) Mannitol 4.) Steroids

Question 41

Acetazolamide

Answer 41

Suppressing cerebrospinal fluid production decreases intracranial pressure

Question 42

Furosemide

Answer 42

Suppressing cerebrospinal fluid decreases intracranial pressure NKCC2 inhibitor

Question 43

Mannitol

Answer 43

Decreases intracranial pressure by osmotic mechanisms

Question 44

Steroids (dexamethasone)

Answer 44

Decreases intracranial pressure by anti-inflammatory mechanisms

Question 45

Cerebral spinal fluid (CSF)

Answer 45

-- Volume = 150 mL -- Rate of production = 550 mL/day -- Lumbar CSF pressure = 70-180 mm CSF -- below 68 mm CSF, absorption stops

Question 46

External hydrocephalus

Answer 46

large amounts of CSF accumulates when the reabsorptive capacity of arachnoid villi decreases

Question 47

Internal hydrocephalus

Answer 47

occurs when Foramina of Luschka and Magendie are blocked or obstruction within the ventricular system, resulting in distention of the ventricles

Question 48

CSF flow pattern

Answer 48

Choroid plexus (epithelial cells) --> lateral ventricles --> interventricular foramen (foramen of Monroe) --> third ventricle --> cerebral aqueduct (Sylvius) --> fourth ventricle --> median foramen/lateral foramen --> subarachnoid space --> sinuses

Question 49

Functions of CSF

Answer 49

1.) Protects brain and spinal cord from trauma 2.) Supplies nutrients to nervous system tissue 3.) Removes waste products from cerebral metabolism

Question 50

Mechanism of CSF formation

Answer 50

Na+ moves down a concentration gradient via secondary active transport (Na+ H+ exchange) in the basolateral membrane. K+, Cl-, HCO3-, diffuse down their electrochemical gradients via ion channels in apical membranes

Question 51

NKCC2 channel transports

Answer 51

-- 1 Na+, 1 K+, and 2 Cl- -- usually driven by a sodium gradient into a cell (does not require energy) -- inhibited by "loop diuretics" such as Furosemide (Lasix)

Question 52

Carbonic anhydrase

Answer 52

-- catalyzes the reaction of CO2 with H2O to form carbonic acid (H2CO3) which dissociates into hydrogen ion (H+) and bicarbonate (HCO3-) --> H+ is exchanged with Na to facilitate Na entry into choroid plexus cells --> Na pumped out by Na-K ATPase --> bicarb is either exchanged for chloride to facilitate chloride entry into CSF or transported into the CSF -- Acetazolamide is a carbonic anhydrase inhibitor (used as a diuretic)

Question 53

Hydrocephalus

Answer 53

-- caused by abnormal accumulation of cerebrospinal fluid (CSF) within the brain ventricles -- excess fluid causes increase in the size of the ventricles and puts pressure on the brain -- damages tissue

Question 54

Congenital hydrocephalus

Answer 54

-- Present at birth or a few weeks/months after birth -- Aqueduct stenosis, chiari malformation, Dany-Walker malformations

Question 55

Acquired hydrocephalus

Answer 55

-- infection (post-meningitis) -- Post hemorrhagic (subarachnoid, intraventricular hemorrhage) -- Tumors

Question 56

Communicating non-obstructive hydrocephalus

Answer 56

-- Impaired cerebrospinal fluid reabsorption -- Due to arachnoidal granulation impairment -- Caused by: subarachnoid/intraventricular hemorrhage, meningitis and congenital absence of arachnoid villi, scarring and fibrosis of the subarachnoid space following infectious, inflammatory, or hemorrhagic events -- Arachnoiditis, post-menigitic venous thrombosis -- Causing diffuse ventricular dilation

Question 57

Non-communicating obstructive hydrocephalus

Answer 57

-- Caused by a CSF flow obstruction -- Tumors, cysts, gliosis in the ventricles, cerebral aqueduct stenosis -- Foramen of Monro obstruction may lead to dilation of one or both lateral ventricles -- Aqueduct of Sylvius, normally narrow to begin with, may be obstructed by a number of genetically or acquired lesions -- 4th ventricle obstruction leading to dilation of the aqueduct as well as the lateral and third ventricles (Arnold Chiari malformation)

Question 58

Arnold-Chiari malformation

Answer 58

Condition in which brain tissue extends into the spinal canal, present at birth

Question 59

Acute hydrocephalus

Answer 59

Develops within days or few weeks: rapid progression of symptoms, requires early attention and treatment-- commonly caused by tumor

Question 60

Chronic hydrocephalus

Answer 60

Develops over months/years, subtle signs of memory impairment, walking difficulty, urinary incontinence. Can also present acutely when pathophysiology changes change the CSF absorption or flow

Question 61

Normal Pressure Hydrocephalus (NPH)

Answer 61

-- Hakim's syndrome -- symptomatic hydrocephalus, a type of brain malfunction caused by expansion of the lateral cerebral ventricles and distortion of the fibers in the corona radiata. -- Symptoms include: urinary incontinence, dementia, and gait disturbances

Question 62

Hydrocephalus symptoms in infants

Answer 62

-- rapid increase in head size -- a bulging or tense soft spot (fontanelle) on the top of the head -- vomiting, sleepiness, poor feeding, seizures, and downward pointing of the eyes (sunsetting), deficits in muscle tone and strength, poor responsiveness to touch, poor growth

Question 63

Hydrocephalus symptoms in toddlers and childrens

Answer 63

- Headache - Blurred vision - Eyes fixed downward - enlargement of head - sleepiness - nausea/vomiting - irritability - delays in walking or talking - unstable balance and poor coordination

Question 64

Hydrocephalus symptoms in young and middle adults

Answer 64

- Headache - Lethargy - Loss of coordination/balance - loss of bladder control - impaired vision - Decline in memory, concentration, and other thinking skills that may affect job performance

Question 65

Hydrocephalus symptoms in old adults

Answer 65

- loss of bladder control or frequent urge to urinate - Memory loss - progressive loss of other thinking or reasoning skills - Difficulty walking, often shuffling gait, or feeling that feet are stuck - poor coordination or balance

Question 66

Diagnosis of hydrocephalus

Answer 66

- history and symptoms - US to visualize the ventricular system - CT/MRI - lumbar puncture in cases of communicating hydrocephalus for both diagnostic and therapeutic

Question 67

Treatment of hydrocephalus

Answer 67

GOAL: reduce fluid volume and pressure, via surgery to remove, shunt to redirect, or drugs to decrease CSF production

Question 68

Ventriculoperitoneal shunt

Answer 68

Diversion of the CSF into another cavity so it becomes absorbed into the bloodstream

Question 69

Prion diseases

Answer 69

- transmissible spongiform encephalopathies (TSE) - 1.) Spongiform neurodegeneration- vacuolation of gray matter, sponge-like appearance on light microscopy - 2.) Amyloid deposits: resistant to proteinase-K digestion and other denaturing agents - 3.) Transmissible

Question 70

Kuru

Answer 70

- Discovered guria, episodes of shivering, partial paralysis, and lack of muscular control leading to death. From Amyloid Kuru plaques in the cerebellum - In fore people: cannibalistic rituals of diseased relatives, including their brains (how transmission occurred) - more common in women>men - progressive cerebellar ataxia --> dementia

Question 71

BSE: Bovine Spongiform Encephalopathy

Answer 71

- Mad cow disease: a progressive neurological disorder of cattle that results from infection by an unusual transmissible agent called a prion. - vCJD 8 year incubation

Question 72

Prion pathology

Answer 72

PrPc --> PrpSc deposition --> synaptic and dendrite loss --> spongiform degeneration --> brain inflammation --> neuronal death

Question 73

Creutzfeldt- Jakob disease

Answer 73

A neurodegenerative condition that is caused by misfolded protein particles (prions). Accumulation of prion particles in the brain eventually leads to neuronal degeneration and clinical onset of the disease. The cardinal symptoms of CJD are rapidly progressive dementia and myoclonus. Most patients die within 12 months following disease manifestation.

Question 74

Symptoms of Creutzfeldt-Jakob disease

Answer 74

- cognitive deterioration, functional decline - horizontal gaze-evoked nystagmus - hyperreflexia - startle myoclonus, ataxia - CSF + for 14-3-3 and tau - real-time quaking induced conversion assay

Question 75

Variant CJD

Answer 75

- a very rare, fatal disease that can infect a person for many years before making them sick by destroying brain cells. Eating beef and beef products contaminated with the infectious agent of bovine spongiform encephalopathy (BSE) is the main cause - onset teens/young adults - cerebellar ataxia --> chorea --> dementia (sCJD) - lymphoreticular system (lymph nodes, spleen, tonsil, appendix) --> peripheral prion replication (oral to brain)

Question 76

Iatrogenic CJD

Answer 76

- where the infection is accidentally spread from someone with CJD through medical or surgical treatment - transplanted corneas, dura mater grafts, blood from vCJD - h-growth hormone, gonadotrophin from cadaveric pituitaries - improperly sterilized depth electrodes

Question 77

Gerstmann-Straussler-Scheinker (GSS) syndrome

Answer 77

- an extremely rare, neurodegenerative brain disorder. It is almost always inherited and is found in only a few families around the world. The disease usually begins between the ages of 35 and 55 - Autosomal dominant, Prnp mutation - Progressive cerebellar ataxia, cognitive decline

Question 78

Fatal familial insomnia

Answer 78

- a remarkably rare and invariably fatal inherited neurodegenerative prion disease. The mode of inheritance of this disease is autosomal dominant and involves a mutation of the prion protein (PRNP) gene, D178N with M129 polymorphism - Clinical: insomnia, dysautonomia, motor and cognitive deterioration, with fast progression to death in months-2 years

Question 79

Prion

Answer 79

- protein-based replicative agents with virus-like properties, including different strains characterized by unique biochemical and clinical features - proteinaceous infectious particles that can shift in molecular weight to protect its core from Proteinase-K and other treatments so that it can survive and spread - PrpSc is the most infectious part-protein, and oligomers

Question 80

Autocatalytic

Answer 80

Seeding nucleation model: oligomers, neuron to neuron or diffusion to spread prion.

Question 81

Example of prion treatment

Answer 81

- Quinacrine (anti-malarial) to prevent PrPSc replication. ONLY WORKS in vitro, does not work in vivo in animals

Question 82

PrP immunotherapy

Answer 82

1.) extracellular protein: easier access by antibodies 2.) Active immunizations: high tolerance to endogenous PrP 3.) Passive: prophylaxis more effective than immunotherapy, no protection after clinical onset/symptoms begin FUTURE: conformational antibodies

Question 83

Diabetic neuropathy

Answer 83

Leads to: - diabetic retinopathy - temperature dysregulation - autonomic dysfunction - incontinence and gastroparesis

Question 84

Neuropathic pain includes

Answer 84

- preserved nociception - Hyperalgesia - Allodynia - Deafferentation

Question 85

Pathways of neuropathic pain

Answer 85

1.) inflammatory processes --> release of sub P from nerve endings --> release of bradykinins, histamine --> sensitization of TRPV1 receptors 2.) In spinal cord --> learning in second order nociceptive neurons --> decreased activity of mechanoreceptors (strengthens interneuron's GABA release) 3.) In central pathways --> rearrangement of synapses

Question 86

Amitriptyline

Answer 86

- TCA that can be used for diabetic neuropathy - Prevents reuptake of NE and 5HT --> enhanced inhibition via descending pathway

Question 87

Duloxetine

Answer 87

- SNRI that can be used for diabetic neuropathy - Prevents reuptake of NE and 5HT specifically --> enhanced inhibition via descending pain pathway

Question 88

Pregabalin

Answer 88

- Anticonvulsant that can be used for diabetic neuropathy - Binds to presynaptic Ca2+ channels --> decreased release of Glu, Sub P, and CGRP from presynaptic nerve terminals

Question 89

Capsaicin

Answer 89

- Analgesic used for diabetic neuropathy - TRPV1 agonist --> degeneration and regeneration of primary afferent nerve terminals --> prevents pain for months - always anesthetize first (painful)

Question 90

Drug interactions of Ms. Moran

Answer 90

Pharmacokinetic - warfarin and amitriptyline - warfarin and metoprolol - warfarin and simvvastatin Pharmacodynamic - amitriptyline + metoprolol --> 2x more fatigue

Question 91

Speech disorders

Answer 91

1. articulation disorder: production of sound error 2. Fluency disorder: rhythm and timing of speech difficulty 3. Voice disorder: quality of voice affected

Question 92

Language disorders

Answer 92

1. Phonological disorders: organizing speech into patterns 2. Apraxia of speech: cannot control speech (thoughts/ muscles) 3. Morphological disorders: adding morphemes incorrectly to words 4. Semantic disorders: poor understanding of word meaning 5. Syntactical deficits: word order and sentence structure deficits 6. Pragmatic difficulties: problems understanding and using language in different social contexts

Question 93

Central auditory processing disorders (CAPD)

Answer 93

Difficulty processing (using and interpreting) sounds. Occurs when the ear and brain do not work smoothly together to interpret sounds

Question 94

Broca's Aphasia

Answer 94

- A lesion of the inferior frontal lobe (Broca's area) - Caused by an infarct involving the superior division of the left middle cerebral artery - Symptoms: Loss of fluency and articulation, inability to repeat complex sentences (language production)

Question 95

Wernicke's Aphasia

Answer 95

- A lesion to the superior temporal lobe (Wernicke's area) - Caused by an infarct involving the inferior division of the left MCA - Symptoms: good fluency, but unintelligible content due to word and phenome choice (phonemic paraphrasia), loss of repetition (speech production-- word salad)

Question 96

Conduction Aphasia

Answer 96

- Damage to the temporal-parietal junction - Left arcuate fasciculus (may be only damage required) - Secondary to any lesion involving the perisylvian - Symptoms: intact comprehension and speech production, some phonemic paraphasic errors, loss of repetition

Question 97

Global Aphasia

Answer 97

- Widespread damage including: basal ganglia, insula, broca's area, wernickes area - Caused by: proximal MCA occlusion affecting both superior and inferior division of the MCA, a large superior division infarct that later becomes a broca's aphasia, large subcortical lesion (hemorrhages, infarcts) Symptoms: loss of language comprehension, speech production, repetition

Question 98

Transcortical Motor aphasia

Answer 98

- Similar to Broca's, damage is in the region anterior to Broca's area - Caused by anterior cerebral artery (ACA-MCA) watershed infarct - Symptoms: Loss of fluency and articulation, intact repetition (SIG DIFF FROM BROCAS)

Question 99

Transcortical sensory aphasia

Answer 99

- Similar to Wernicke's, damage to region inferior to Wernicke's - caused by PCA-MCA watershed - Symptoms: effortless speech, unintelligible content due to word and phoneme choice errors (phonemic paraphasias), * intact repetition

Question 100

Transcortical mixed aphasia

Answer 100

- Similar to Broca's/Wernicke's mix - Caused by ACA-MCA, or PCA-MCA infarct - Symptoms: Loss of fluency and articulation, difficulty initiating speech, Language comprehension impairments, *intact repetition

Question 101

Subcortical aphasia

Answer 101

- Damage to Left thalamus, or Left caudate - Symptoms: impaired language production, dysarthria (dysfxn of mouth and larynx muscle control)

Question 102

Paraphasia

Answer 102

- a feature of other aphasias: 1.) neologistic: invention of new words 2.) semantic: word substitution with similar meaning 3. ) Phonemic: sound substitution

Question 103

Anomia

Answer 103

- Caused by lesion to left parietal, posterior to Wernicke's - Symptoms: highly specific deficit, difficulty remembering words, normal speech fluency

Question 104

Alexia

Answer 104

Disruption of the ability to read. Vision-dependent, disruption of transfer of vision to lateralized speech areas (splenium injury)

Question 105

Agraphia

Answer 105

Disruption of the ability to write. Vision-dependent, disruption of transfer of vision to lateralized speech areas (splenium injury disrupts reading in the left visual field)

Question 106

Apraxia

Answer 106

- seen in 1/3 of all aphasics - Caused by lesion to precentral gyrus of the insula - Symptoms: difficulty in mouth movement sequences

Question 107

Transcranial Magnetic Stimulation

Answer 107

- action potential propagation in axons - creates charge difference along axons - summed across millions of neurons - stimulation can induce transient aphasia

Question 108

Cellular pathology of CNS damage

Answer 108

1. Neuronal: red neurons, axonal swelling 2. Astrocytes: gemistiocytic change 3. Microglia: nuclear elongation 4. Oligodendrocytes: apoptosis, demyelination

Question 109

Neuronal death in TBI mechanisms

Answer 109

1. direct physical damage 2. necrosis from release of excitatory transmitters such as glutamate 3. diffuse delayed cell death --> necrosis pathway, apoptosis pathway

Question 110

Neuronal death contributing factors

Answer 110

- Focal ischemia - Loss of blood brain barrier - Inflammation - Cytokine release

Question 111

Cell body changes during axonal regeneration seen in anterior horn when motor axons are damaged or severed

Answer 111

- increased protein synthesis, cell body enlargement, lateral nuclear displacement - Bulb-like swelling 24 hours post on H&E stain - Bulb-like swelling and varicose axonal changes on immunoperoxidase stain for beta-APP within 2 hours

Question 112

Patterns of beta-APP IHC patterns of axonal swelling

Answer 112

1. Traumatic: diffuse and more linear/twisted distribution 2. Infarct: outlines border of infarct, more punctate distribution

Question 113

Diastatic fracture

Answer 113

widens suture lines

Question 114

Basal skull fractures

Answer 114

- serious fracture, most commonly involving petrous portion of temporal bone, external auditory canal, and TM - Cranial nerve or cervicomedullary symptoms accompanied by orbital or mastoid hematomas (bruises), CSF leak may occur from nose or ear

Question 115

Linear skull fractures

Answer 115

- most common - Straight crack in the bone with no displacement - hairline: vault of the skull - Basilar: in the skull base - Diastatic: run into and widen skull suture

Question 116

Parenchymal injury

Answer 116

- Concussion: clinical syndrome of altered consciousness secondary to head injury, onset of transient neurological dysfunction - Pathogenesis: Downregulation of reticular activating system, repetitive concussions --> permanent cognitive impairment (CTE) - Most common: Frontal, temporal, and orbital ridge

Question 117

Contusion Coup

Answer 117

Bruise of the brain with intact pia, at the point of contact (object moving and immobile head)

Question 118

Contusion Contrecoup

Answer 118

Bruise of the brain with intact pia, diametrically opposite to the point of contact (object moving and mobile head)

Question 119

CNA trauma- Laceration

Answer 119

- Tearing of brain tissue disrupting the pia - Caused commonly by sudden violent impacts resulting in posterior or lateral neck hyperextension of the neck can result in sudden death due to avulsion of pons from medulla, or medulla from cervical cord

Question 120

Cellular pathology of a contusion

Answer 120

- Pericapillary hemorrhage - axonal damage - red neurons first, axonal swelling second - early changes of contusion - Gross: full thickness hemorrhage into the cortex grey matter at the crest of the gyrus, wedge shaped cross section with the wide base at the surface

Question 121

Plaque Jaune

Answer 121

retracted, yellow brown lesions involving crest of gyri, seizure foci

Question 122

Parenchymal injury-- diffuse axonal injury

Answer 122

- deep white matter regions affected - supratentorial: corpus callosum, paraventricular, hippocampus - infratentorial: cerebellar peduncles, brachium conjunctivum, superior colliculi, deep reticular formation - twisting and shearing of axons in severe trauma (shaken baby, boxing) - common cause of persistent deficits or coma after trauma

Question 123

Diffuse traumatic injury

Answer 123

- hemorrhages in corpus callosum and cerebral peduncles - Small scattered hemorrhages in cerebral hemispheric white matter (most pronounced in anterior frontal lobes) - Fat/bone marrow embolism from bodily injuries and destroyed cells can deposit in the brain

Question 124

Vascular injury

Answer 124

- Common in traumatic brain injury and results from direct trauma and disruption of the vessel wall with extravasation of blood - Epidural, subdural (trauma), subarachnoid (aneurysm), intraparenchymal (cerebral amyloid, lobar, and hypertensive, ganglionic)

Question 125

Epidural hematoma

Answer 125

- Dural arteries (middle meningeal) are vulnerable to injury - slow accumulation: patient lucid several hours before symptoms - Rapid accumulation: neurosurgical emergency for drainage

Question 126

Subdural hematoma

Answer 126

- between dura and outer arachnoid, external layer: collagenous, inner border: cell layer with fibroblasts and abundant extracellular space devoid of collagen - Caused by bridging veins that tear - can be acute, or chronic, compresses underlying brain. Slower onset (48hrs) because veins are slower flow

Question 127

Spinal cord injury histology

Answer 127

- hemorrhage, necrosis, and axonal swelling in surrounding white matter

Question 128

Sequelae

Answer 128

- posttraumatic hydrocephalus due to obstruction of CSF resorption from hemorrhage in subarachnoid spaces - Chronic Traumatic Encephalopathy: dementing illness following repetitive trauma. Atrophy, enlarged ventricles, tau accumulation, NFTs, in superficial frontal and temporal lobe cortex

Question 129

Chronic Traumatic Encephalopathy (CTE)

Answer 129

- associated with contact sports, military training, and combat - repetitive concussions - Symptoms: 8-10 years later, HA, loss of attention, short term memory loss, behavior changes, dementia, and gait abnormality

Question 130

CTE in younger vs older patients

Answer 130

Younger: more pronounced behavior and mood changes Older: more pronounced cognitive impairment Both: reduced brain weight, enlarged lateral and third ventricles, thinning of corpus collosum, cavum/septum pellucidum with fenestrations, scarring and loss of neurons of cerebellar tonsils

Question 131

Neuropathology of CTE

Answer 131

- Deposition of hyperphosphorylated tau in NFTs, threads of astrocytes and TDP-43 - Tau focal findings esp in cerebral sulci surrounding and penetrating cortical vessels (in the grey matter) - Stages 1 and 2: cortical pathology - Stages 3 and 4: more extensive subcortical involvement

Question 132

CTE clinical pathology

Answer 132

- Papez circuit involvement: behavioral changes - Hippocampus, entorhinal cortex, medial thalamus: Memory changes - Dorsolateral parietal, posterior temporal, occipital involvement: visual changes - Substania nigra: parkinsonian movements

Question 133

Components of anesthetic state include:

Answer 133

- Amnesia - Immobility in response to noxious stimulation - Attenuation of automatic responses to noxious stimulation - Analgesia - Unconsciousness

Question 134

Inhaled volatile anesthetics

Answer 134

- Halothane, enflurane, isoflurane, desflurane, sevoflurance - high boiling points (relative to gaseous) - Liquid at room temp - Administered using vaporizers - higher lipid solubility (LOWER MAC) - higher blood solubility (slower induction and recovery) - slower and more potent

Question 135

Inhaled gaseous anesthetics

Answer 135

- Nitrous oxide, xenon - Low boiling point - gas at room temperature - lower blood solubility - lower lipid solubility (lower potency) - HIGHER MAC

Question 136

Pharmacokinetics of inhaled anesthetics

Answer 136

- taken up through gas exchange in the alveoli of the lung - rapid onset, rapid termination - Effect site concentration in the CNS (brain and spinal cord) will need to change rapidly

Question 137

Factors controlling uptake of inhaled anesthetics

Answer 137

1. inspired concentration and ventilation 2. anesthetic solubility (blood:gas partition coefficient) 3. Cardiac output 4. Alveolar-venous partial pressure difference

Question 138

Alveolar concentration and inspired concentration

Answer 138

The faster FA/Fi approaches 1 (inspired-to-alveolar equilibrium), that faster anesthesia will occur during an inhaled induction

Question 139

What is the key factor influencing the transfer of anesthetic from lungs --> arterial blood? (gas uptake)

Answer 139

Blood solubility

Question 140

Henry's law

Answer 140

- number of gas molecules that enter a liquid before equilibrium is reached is determined by the solubility of the gas in the liquid - more anesthetic dissolved in blood --> longer it takes to obtain equilibrium and greater concentration of anesthetic is required - the fastest acting drug is the least soluble in blood

Question 141

Cerebral effects of inhaled anesthetics (Guedel's signs of CNS depression)

Answer 141

1.) analgesia, late stage one = amnesia 2.) excitement (BAD) = increased vital signs, rapid onset drugs decreases the amount of time spent in stage 2 3.) surgical anesthesia, desired stage of slowed HR and RR, spontaneous apnea occurs 4.) medullary depression (BAD), vasomotor depression leading to lack of support for the circulatory and respiratory symptoms

Question 142

Metabolism of enflurane may generate:

Answer 142

nephrotoxic compounds, like fluoride ions when metabolized in the liver

Question 143

Halothane hepatitis

Answer 143

fulminant hepatic failure after halothane

Question 144

Malignant hyperthermia

Answer 144

- from inhaled anesthetics - imbalance electrolytes, leading to muscle rigidity, hyperthermia, tachycardia, hypercapnia, hyperkalemia, metabolic acidosis -- can also be triggered by succinylcholine causing an increase in free cytosolic Ca2+ concentration in skeletal muscle cells

Question 145

Treatment for inhaled anesthetic malignant hyperthermia

Answer 145

Dantrolene-- reduces Ca2+ release from the sarcoplasmic reticulum

Question 146

IV anesthetics that are Lipophilic and preferentially partition into highly perfused lipophilic tissues (brain, spinal cord) leads to

Answer 146

rapid onset of action

Question 147

Termination of the effect of a single bolus is determined by:

Answer 147

Redistribution of the drug into less perfused and inactive tissues (skeletal muscle --> fat)

Question 148

Propofol

Answer 148

- IV anesthetic used for induction of anesthesia - Poor solubility in water - Potentiation of GABAA chloride current - Rapidly metabolized in the liver

Question 149

Drug half-lives and durations of action are dependent on a complex of interactions:

Answer 149

1. rate of distribution 2. amount of drug accumulated in fat 3. drug's metabolic rate

Question 150

Propofol effects in the body

Answer 150

1. CNS- hypnotic, decreases cerebral blood flow and metabolic rate 2. Cardiovascular- decreases blood pressure, inhibits baroreceptor reflex 3. Respiratory- potent depressor (ventilation used) 4. antiemetic properties- less nausea after waking

Question 151

Barbiturates as anesthetics

Answer 151

- Thiopental, methohexital - enhancement of inhibitory GABA transmission - not suitable for continuous infusion (bolus only) because of long context-sensitive elimination half time - used for inductions only

Question 152

Barbiturate effects on the body

Answer 152

1. CNS- depression, decreases cerebral blood flow 2. Cardiovascular- decrease blood pressure, increase HR because no inhibition of the baroreceptor reflex 3. Respiratory- depressant and bronchospasm

Question 153

Benzodiazepines as anesthetics

Answer 153

- Midazolam, Diazepam - anxiolytics, anterograde amnesia - used preoperatively to prepare for surgery - action can be terminated by: FLUMAZENIL

Question 154

Benzodiazepine effects on the body

Answer 154

1. CNS- decrease CMR and cerebral blood flow 2. Cardiovascular- decreases blood pressure 3. Respiratory- transient apnea, and post-operative respiratory depression (WATCH FOR)

Question 155

Etomidate as anesthetics

Answer 155

- hypnotic but not analgesic - minimal hemodynamic effects - used for pts with compromised myocardial activity - Mech: potentiation of GABAA mediated chloride currents

Question 156

Etomidate effects on the body

Answer 156

1. CNS- decreases cerebral blood flow 2. Cardiovascular- stability after bolus 3. Endocrine- Adrenocortical suppression (no continuous use- bolus) by inhibition of 11beta-hydroxylase which converts cholesterol to cortisol

Question 157

Ketamine as an anesthetic

Answer 157

- highly lipid-soluble phencyclidine (PCP) derivative - significant analgesia - NMDA receptor antagonist - metabolized in the liver

Question 158

Ketamine effects on the body

Answer 158

1. CNS- increases cerebral flow (diff from all other anesthetics) 2. Cardiovascular- CV stimulant, increases BP, HR, and RR, and cardiac output (from sympath NS stim) 3. Respiratory- bronchodilation -- Unpleasant emergence reactions: hallucinations, vivid dreams, euphoric state, less frequent in CHILDREN, so ketamine is used more frequently in kids

Question 159

Neuromuscular blockers

Answer 159

- Blocks cholinergic transmission at the neuromuscular junction - relaxes muscles and diminishes reflexes, useful in surgery

Question 160

Non-depolarizing neuromuscular blockers

Answer 160

- Atracurium, mivacurium, pancuronium, rocuronium, vecuronium, tubocurarine - Competitive antagonists, block ACh binding site on nicotinic receptor - REVERSED BY neostigmine

Question 161

Depolarizing neuromuscular blockers

Answer 161

- Succinylcholine - Nicotinic receptor agonist, not metabolized by acetylcholinesterase - Continuous stimulation of receptor which maintains the depolarized state (phase 1 blockade because the membrane cannot repolarize) -phase 2 blockade when the muscles become unresponsive

Question 162

Adverse effects of neuromuscular blockers

Answer 162

1. non-depolarizing: histamine release 2. Succinylcholine- risk for hyperkalemia and cardiac arrhythmias and malignant hyperthermia (increase K+ release from muscles, and Ca2+ free in the cytosol)

Question 163

WHO Grade 1 CNS tumors

Answer 163

- generally low proliferative potential, possible to cure following resection alone (meningiomas often have a good outcome)

Question 164

WHO Grade 2 CNS tumors

Answer 164

- Generally infiltrative but low proliferative activity, if removed will often recur or progress - Diffuse astrocytomas which may progress to grade 3 or 4 - Survival rate: generally greater than 5 years

Question 165

WHO Grade 3 CNS tumors

Answer 165

- histological features of malignancy - nuclear atypia and much mitotic activity - patients usually receive surgery, radiation, and/or chemo - Survival rate: generally 2-3 years

Question 166

WHO Grade 4 CNS tumors

Answer 166

- Cytologically malignant, mitotically active, NECROSIS prone - Rapid pre- and post- operative disease progression, usually fatal outcome - Survival rate: depends on treatment-- in the elderly, often not more than 1-2 years

Question 167

CNS tumors prognosis is determined by

Answer 167

- grade - age - location - performance status - radiological features - extent of resection - proliferation index - genetic alterations

Question 168

CNS metastasis

Answer 168

- 25-50% of intracranial tumors - most common area to metastasize from: lung, breast, skin (melanoma), kidney, and GI tract - Choriocarcinoma is a tumor that commonly metastasizes to the brain, but it is rare - prostate cancer can sometimes metastasize to brain - meninges can frequently be involved

Question 169

What does a metastasized tumor to the CNS look like?

Answer 169

1. well circumscribed 2. bright with contrast 3. tend to have multiple tumors 4. Usually located in the junction between gray and white matter

Question 170

What does a primary brain tumor of the CNS generally look like?

Answer 170

1. Poorly circumscribed 2. Usually single 3. Location varies by specific type (originating from the brain)

Question 171

Meningioma

Answer 171

• second most common primary intercranial tumor after gliomas • predominantly benign tumors of adults • usually attached to the dura • arise from the meningothelial cells of the arachnoid • extra-axial rounded masses on imaging • sphenoid wing

Question 172

WHO Grade 1 meningiomas (majority)

Answer 172

• meningothelial (whorled) • fibrous • transitional (both meningothelial and fibrous together)

Question 173

Molecular genetics of meningioma

Answer 173

• loss of chromosome 22 • long arm is most frequently seen genetic abnormality, including the region with NF2 gene • NF2 absent, TNF receptor associated factor 7 (TRAF7) most common

Question 174

WHO 1 meningothelial histology

Answer 174

• whorled clusters of cells in tight groups without visible cell membranes (syncytial) • no cytologic atypia, few mitoses • may also see purple calcified psammoma bodies

Question 175

WHO 1 fibrous meningioma histology

Answer 175

• elongated, delicate skin cells with variable amount of pink collagen between the cells

Question 176

Meningioma histology staining

Answer 176

• can express Vimentin and epithelial membrane antigen by IHC • Ki-67 staining to assess proliferation rate • extension in the bone does not alter the histologic grade

Question 177

Spinal meningioma: more common in males, or females?

Answer 177

Females, 10:1

Question 178

If there are multiple meningiomas, what should you consider?

Answer 178

Neurofibromatosis type 2

Question 179

Neuroectodermal tumor

Answer 179

• Express few, if any markers of typical mature neural cells, they retain cellular features of primitive undifferentiated cells

Question 180

Medulloblastoma

Answer 180

• embryonal neoplasm • intra-axial • accounts for 20% of tumors in children— midline, cerebellar location • largely undifferentiated and always a WHO grade 4

Question 181

Alterations in what signaling pathways can lead to medulloblastoma?

Answer 181

1.) sonic hedgehog-patched pathway (SHH)— best prognosis 2.) WNT/beta catenin signaling pathway — MYCN amplification, worse outcome if p53 mutation 3.) group 3– MYC amplification, and isochromosome 17 (i17q) 4.) i17q without MYC amplification, prognosis worse than SHH but not as bad as group 3

Question 182

Medulloblastoma histology

Answer 182

• small round blue cell tumor • background Neuropil • Homer-Wright Rosettes

Question 183

What is at the center of a pseudo rosette?

Answer 183

Central blood vessel

Question 184

What is at the center of a homer-wright rosette?

Answer 184

Neuropil in the center— indicative of medulloblastoma

Question 185

What is at the center of a flexor-wintersteiner rosette?

Answer 185

Cytoplasmic extensions in the center— indicative of retinoblastoma, primitive cancer of childhood

Question 186

Germ cell tumors of the CNS

Answer 186

• midline, location, pineal and suprasellar location • 90% of her in the first two decades, with a male predominant • similar histology to gonadal or mediastinal tumors

Question 187

Germinoma

Answer 187

• a tumor that is morphologically similar to testicular seminoma • very responsive to chemotherapy and radiation therapy • CSF levels of protein markers can be used for diagnosis (alpha fetoprotein, and beta human chorionic gonadotropin)

Question 188

Germinoma histology

Answer 188

• large tumor cells, pale glycogen rich • background, benign lymphocytes, occasionally multi nucleated cells express HCG, and placental alkaline phosphatase (PLAP)

Question 189

Primary CNS lymphoma

Answer 189

• most common CNS neoplasm in immunocompromised individuals • frequency increases after age 60 • systemic lymphoma involving the brain is very rare • multifocal, extension outside of the CNS is rare

Question 190

A vast majority of primary CNS lymphoma are:

Answer 190

B cell type. They are aggressive and have worse outcomes then tours of similar histology outside of the CNS. Nearly all primary CNS lymphomas have latent Epstein-Barr virus • biopsy before using steroids, because steroids can compromise histologic evaluation (by causing apoptosis)

Question 191

Description of primary CNS lymphoma

Answer 191

• multifocal, deep, gray matter involvement, as well as white matter and cortex • well defined masses, compared to gliomas, but not as discreet as metastases • DLBCL is the most common type, and expresses CD 20 to have a high growth fraction

Question 192

Primary CNS lymphoma histology

Answer 192

• solid growth with a diffuse pattern • mitotic activity • kappa, or lambda light chain restriction • infiltrative, and perivascular distribution • CD-20 IHC

Question 193

Schwannoma

Answer 193

• intracranial, 8% of neoplasms • more common and 50 to 60 year olds • vestibular branch of the eighth cranial nerve involvement causes an acoustic neuroma

Question 194

Spinal schwannoma

Answer 194

• predominantly arise in sensory nerve roots • lumbosacral most common • intradural, and extramedullary • grow through foramen and have characteristic dumbbell shapes • cerebellum Pontine angle tumor

Question 195

Schwannoma histology

Answer 195

• spindle cell mesenchymal neoplasm with Schwann cell differentiation • biphasic: Antoni A and Antoni B • verocay body (zone with no nuclei, but nuclei lining around it) • GFAP negative, S 100 positive (neural derived) • cerebella’s pontine angle

Question 196

Three major subtypes of gliomas

Answer 196

• oligodendroglioma • ependymoma • astrocytoma — characteristic histology is the basis for classification

Question 197

WHO grade 1 glioma

Answer 197

Pilocytic Astrocytoma

Question 198

GFAP

Answer 198

• glial fibrillary acidic protein • principal intermediate filament in mature glial cells • modulates, astrocyte, motility, and shape • Astrogliosis- rapid synthesis of GFAP

Question 199

Pilocytic astrocytoma

Answer 199

• WHO 1 glioma • children and young adults • usually cerebellum, also third ventricle, optic nerves, and cerebellar hemispheres • distinction from other astrocytomas, supported by lack of p53 mutations • very slow growth, symptomatic recurrence related to enlarging cystic component

Question 200

Two alterations of the BRAF, signaling pathway that are seen with a pilocytic astrocytoma

Answer 200

1.) duplication 2.) mutation V600E

Question 201

Pilocytic astrocytoma histology

Answer 201

• biphasic histology • loose with micro cysts • compact fascicular • bipolar cells with long hairlike fibers • Rosenthal fibers *** • eosinophilic elongated, carrot shaped or corkscrew shaped inclusions

Question 202

Ependymoma

Answer 202

• a circumscribed glioma composed of uniform, small cells with round nuclei in a fibrillary matrix and characterized by perivascular anucleate zones and ependymal rosettes • cuboidal cells forming true rosettes • Low cell density and low mitotic count • primarily intracranial, posterior fossa location typical in childhood tumors

Question 203

Ependymoma histology

Answer 203

• bland cells cytologically • perivascular • pseudorosettes are common • GFAP positive IHC • occasional ependymal canals

Question 204

A posterior fossa ependymoma tumor often manifests with:

Answer 204

• Hydrocephalus secondary to obstruction of the fourth ventricle • CSF dissemination is fairly common and has a worse prognosis

Question 205

Subependymoma

Answer 205

Slow, growing, usually incidental autopsy finding protruding into a ventricle

Question 206

Choroid plexus papilloma

Answer 206

Occur anywhere along the choroid plexus, most common in children, hydrocephalus due to obstruction, and can be malignant— choroid, plexus carcinoma. RARE

Question 207

Colloid cyst of the fourth ventricle

Answer 207

• Non-neoplastic enlarging cyst. Found in young adults at the roof of the third ventricle. • obstructs foramen of Monro, causing hydrocephalus • flat cuboidal epithelial lining containing gelatinous/proteinaceous material

Question 208

Oligodendrolgioma, IDH mutant and 1p/19q codeleted

Answer 208

• diffusely infiltrating glioma of cells resembling oligodendrocytes • cerebral hemisphere involvement, white matter • only WHO grades 2 (well differentiated) and 3 (can a plastic tumors- include CDKN2A mutation)

Question 209

Oligodendrolgioma, IDH mutant and 1p/19q codeleted description

Answer 209

• expanded gyri and deep white matter • distorted striatum and lateral ventricle • subfalcine herniation

Question 210

Oligodendrolgioma, IDH mutant and 1p/19q codeleted histology

Answer 210

• round tumor cell nuclei • clear cytoplasm- halos • thinly walled capillary vasculature • calcification is common • FRIED EGG APPEARANCE

Question 211

Diffuse astrocytoma, IDH mutant

Answer 211

• infiltrating astrocytoma accounts for 80% of adult primary brain tumors • usually found in the cerebral hemispheres, less common in the cerebellum, brainstem, and spinal cord • presents with seizures, headaches, focal deficit related to location • there is no grade 1 (only 2-4)

Question 212

Diffuse astrocytoma, IDH mutant description

Answer 212

• slow growth • high degree of cell differentiation • commonly affects young adults • frontal lobe location is typical • WHO grade 2 • can progress to higher grades and recur

Question 213

Diffuse astrocytoma, IDH mutant grade 2 histology

Answer 213

• increased cellularity compared to normal white matter • find meshwork of GFAP positive astrocytic processes • fibrillary appearing background • indistinct transition to normal tissue— complete excision is difficult

Question 214

Anaplastic astrocytoma, IDH mutant, WHO grade 3

Answer 214

• diffusely, infiltrating astrocytoma with focal or dispersed, in a pleasure, significant proliferative activity, and a mutation in the IDH1 or IDH2 gene • histology: increased atypia and mitoses, cells are bigger, more of them

Question 215

Glioblastoma— WHO grade 4B

Answer 215

• all the features of WHO 3 astrocytoma with the addition of necrosis, and increased microvascular proliferation • palisading necrosis • intra axial

Question 216

Cowden Syndrome

Answer 216

dysplastic Gangliocytoma— PTEN mutation

Question 217

Li-Fraumeni Syndrome

Answer 217

Medulloblastoma, mutated p53

Question 218

Turcot syndrome

Answer 218

Medulloblastoma or glioblastoma, mutated APCor mismatch repair

Question 219

Gorlin syndrome

Answer 219

Medulloblastoma, mutation of PTCH-SHH pathway

Question 220

Tuberous sclerosis

Answer 220

• autosomal, dominant • hamartomas, and benign neoplasms of the brain and other tissues • seizures, autism, mental retardation • cortical, tubers and suependymal nodules • TSC1- hamartin • TSC2- tuberin

Question 221

Von Hippel-Lindau disease

Answer 221

• autosomal, dominant • CNS hemangioblastomas and cysts of the liver, pancreas and kidneys • also develop renal cell carcinoma and pheochromocytoma • VHL gene, tumor suppressor mutated

Question 222

Neurofibromatosis

Answer 222

• NF1: peripheral nerve neurofibromas, optic nerve gliomas, pigmented, nodules of the Iris (lisch), cutaneous, hyperpigmented macules (café au lait spots) • NF2: bilateral schwannomas of cranial nerve 8, multiple meningiomas, gliomas- spinal ependymoma

Question 223

Anxiety disorders

Answer 223

• panic disorder • agoraphobia • specific phobia • social anxiety disorder • generalized anxiety disorder • separation anxiety disorder

Question 224

Panic disorder

Answer 224

• recurrent unexpected panic attacks, with at least one of the attacks being followed by one month of: 1. Persistent concern, or worry about additional panic attacks or their consequences. 2. A significant maladaptive change in behavior related to the attacks.

Question 225

Agoraphobia

Answer 225

• market, fear, or anxiety for more than six months, about two or more of the following five situation: 1. Public transportation. 2. Being in open spaces. 3. Being in enclosed spaces. 4. Standing in line or being in a crowd. 5. Being outside of the home alone.

Question 226

Social phobia

Answer 226

An intense fear of becoming humiliated in a social situation, specifically of embarrassing yourself in front of other people

Question 227

Generalized anxiety disorder

Answer 227

• excessive worry more days than not for at least six months about a number of events they find difficult to control the worry for • three or more of the following symptoms: restlessness, on edge, easily fatigue, difficulty concentrating, irritability, muscle tension, sleep disturbance

Question 228

Obsessive, compulsive and related disorders

Answer 228

1. Obsessive compulsive disorder. 2. Hoarding disorder. 3. Body dysmorphic disorder. 4. Trichotillomania (hair pulling disorder) 5. Excoriation disorder. (skin picking.)

Question 229

Treatment for OCD

Answer 229

• cognitive behavior therapy • education, restaurants, elimination of caffeine, alcohol, drugs, and over-the-counter stimulants • medication, such as SSRIs, and then our eyes, tricyclics, MAOIs, benzodiazepines, valproate, gabapentin

Question 230

Behavioral model of anxiety: two factor learning theory

Answer 230

• neutral, stimulus paired with an anxiety provoking stimulus —> later than neutral, stimulus, provokes, anxiety, response, and avoidance behavior —> avoidance is reinforced by the reduction of anxiety

Question 231

Distinction between schizophrenia and episodic manic psychosis

Answer 231

1. Inter-episodic clearing versus persistent, psychosis features 2. Intra-episode unique high energy features of mania

Question 232

Bipolar 1 disorder

Answer 232

• a distinct period of elevated expensive irritable mood last in one week or more • +3 more symptoms, including: grandiosity, decreased sleep need, pressured speech, flight of ideas, distractibility, increased in goal-directed activity • severe enough to cause marked impairment in usual functioning

Question 233

Bipolar 2 disorder

Answer 233

• hypomania- usually perceived as a positive experience, such as “ on top of things”, sociable, productive, self-confident • does not meet full meaning of criteria or impairment in usual functioning

Question 234

Ultra rapid cycling of bipolar disorder

Answer 234

4+ episodes in 12 months of mania

Question 235

Disruptive mood dysregulation disorder

Answer 235

• can be mistaken for bipolar and children • severe recurrent temper outbursts in response to common stressors • at least three times per week for over a year and occurs in at least to settings • disproportional to stressors, developmental level

Question 236

Narrow phenotype bipolar disorder

Answer 236

DSM textbook patient, including duration and hallmark symptoms of elation in grandiosity

Question 237

Intermediate phenotype 1 of bipolar disorder

Answer 237

Episodic hallmark symptoms present, but duration criteria is not met

Question 238

Intermediate phenotype 2 for bipolar disorder

Answer 238

Episodic, but irritable mood only (no elation, grandiosity as hallmarks)

Question 239

Broad phenotype (ie DMDD)

Answer 239

Chronic non-episodic without Hallmark symptoms, but has irritability and hyperarousal

Question 240

What two processes influence the development of emotional regulation?

Answer 240

1.) attachment: temperament 2.) cognitive development: external to internal control, public to private speech, etc.

Question 241

Examples of abnormal emotional regulation development

Answer 241

1.) reactive attachment disorder 2.) infants of depressed mothers 3.) fetal alcohol spectrum disorder 4.) post traumatic stress disorder 5.) personality disorders

Question 242

Neurophysiology of bipolar disorder

Answer 242

• deactivation in the inferior frontal cortex or eventual lateral prefrontal cortex- particularly in mania, but not euthymic and depressed state • limbic hyperactivity in individuals with bipolar disorder

Question 243

Top-five checklist for evaluation of bipolar disorder

Answer 243

1.) developmental history 2.) genetic history 3.) medical history 4.) Psychological History to help define patterns of emotion/behavior dysregulation 5.) do a stress inventory to examine disregulating factors

Question 244

Laboratory studies for new onset mania to help rule out other things

Answer 244

• CT/MRI • STD screening— RPR, HIV • CBC • urine drug screen • serum therapeutic drug levels (anticonvulsants) • vitamin B12 level • thyroid function • anti-NMDA receptor antibodies, and CSF, less often in serum if features suggestive of encephalitis • EEG

Question 245

DSM axis I vs axis II

Answer 245

• axis I: mood, anxiety, attentional, substance use disorders • axis II: personality disorders

Question 246

General personality disorder definition

Answer 246

Enduring pattern of inner experience and behavior that deviates markedly from the expectations of individual’s culture • cognition, affectivity, interpersonal function, impulse control

Question 247

What are the only drugs proven to have anti-suicide effects?

Answer 247

Clozapine and lithium

Question 248

Mood stabilizer drugs used for bipolar disorder

Answer 248

• lithium carbonate • divalproex sodium (depakote) • carbamazepine (tegretol) • lamotrigine (Lamictal) • topiramate (Topamax) • oxcarbazepine (Trileptal)

Question 249

Lithium carbonate

Answer 249

• one of only two psychiatric medication’s that demonstrate affect on reducing suicidal thoughts and behavior • titrated to serum level of 0.6 to 1.2 • lab monitoring necessary for possible hypothyroidism, renal insufficiency risk of lithium toxicity

Question 250

Sodium divalproex (depakote)

Answer 250

• efficacy equal to lithium • titrated to serum level of 50 to 100 • laboratory monitoring, needed to monitor risks, including hepatotoxicity and thrombocytopenia

Question 251

Carbamazepine (Tegretol)

Answer 251

• anticonvulsant, nearly as effective as lithium • titrated to serum level of 4 to 10 • laboratory monitoring, needed to monitor for potential agranulocytosis and hepatotoxicity

Question 252

Three primary algorithms for evidence-based pharmacologic treatment of bipolar disorder

Answer 252

1.) Treatment of acute mania 2.) treatment of a cute/chronic depression 3.) maintenance treatment (prevention of future episodes)

Question 253

The Texas medication algorithm method

Answer 253

• treatment of acute mania, relying on monotherapy with mood stabilizer or a neuroleptic (stage 1: lamotrigine +/- mood stabilizer) • if nonresponsive change to dual therapy with mood stabilizer and neuroleptic (stage 2: quetiapine + fluoxetine combo) • later stages of the algorithm include clozapine and ECT (stage 3: other anti-depressants + anti-manic agents)

Question 254

Sedative, hypnotic drugs, and their dose related to CNS depression

Answer 254

Relief of anxiety —> sedation —> hypnosis —> general anesthesia —> death

Question 255

Anxiolytic

Answer 255

Patient is relaxed, less concerned with surroundings and fully functional

Question 256

Sedative

Answer 256

Decreased activity, moderates excitement and calms patient. Patient is awake, impairment of psychomotor functions

Question 257

Hypnotic

Answer 257

Facilitates the onset and maintenance of sleep and increases the duration of the sleep state. Patient may be easily aroused.

Question 258

General anesthetic

Answer 258

A state in which there is a loss of consciousness, from which the patient cannot be aroused

Question 259

The linear slope versus nonlinear slope of sedative hypnotic drugs

Answer 259

Linear slope: typical of older, sedative hypnotics, such as barbiturates. Increase in those higher than that needed for hypnosis may lead to a state of general anesthesia. (zero order kinetics) Nonlinear slope: typical of benzodiazepines and newer drugs. Requires proportionally, greater dosages to achieve CNS depression (less dangerous) (first order)

Question 260

Barbiturate examples

Answer 260

• phenobarbital (long acting) • pentobarbital (short/intermediate acting) • secobarbital (short/intermediate acting) • thiopental (ultra short acting)

Question 261

Barbiturates GABA pharmacology

Answer 261

• potentiates GABAergic inhibition at many levels • enhances GABA effects, positive allosteric modulators • increases the DURATION of the GABA gated chloride channel openings

Question 262

Barbiturates, absorption and redistribution

Answer 262

• absorbs rapidly into the blood following oral administration (IV for anesthetic induction) • highly lipid soluble (thiopental) is faster than less lipid soluble (phenobarbital)

Question 263

Barbiturates excretion

Answer 263

• phenobarbital: 25% excreted unchanged • a weak acid with a PKa of 7.4 • increasing urinary pH leads to increased drug excretion ( sodium bicarbonate can do this)

Question 264

People with porphyria, when given barbiturates

Answer 264

Have a porphyrin (precursor of heme) build up an acute attack (therefore contraindicated)

Question 265

Phenobarbital is effective in the treatment of:

Answer 265

Many things, but focal and generalized tonic clonic seizures from alcohol withdrawal

Question 266

Withdrawal syndrome symptoms from barbiturates

Answer 266

Increased anxiety, insomnia, central nervous system excitability that made progress to convulsions (dangerous)

Question 267

Benzodiazepines

Answer 267

Long acting: 1. diazepam 2. Flurazepam 3. Chlordiazepoxide Intermediate acting 1. Lorazepam Short acting 1. Alprazolam 2. Triazolam 3. Oxazepam 4. Midazolam

Question 268

Benzodiazepine pharmacology

Answer 268

• potent GABAergic inhibition (agonist) at many levels, increases the efficacy of GABAergic synaptic inhibition • increases the FREQUENCY of chloride channel opening events • triazolam is extremely rapid, an extremely lipid soluble

Question 269

Desmethyldiazepam

Answer 269

An active metabolite of diazepam as a result of the breakdown of a long, half-life drug (40 hour half-life for diazepam)

Question 270

Benzodiazepine sedation

Answer 270

• they also exert dose-dependent anterograde amnesia effects

Question 271

Benzodiazepines have what effect on sleep?

Answer 271

• induces sleep at high enough doses • more rapid onset of sleep and prolongation of stage 2 sleep

Question 272

What is the reversible drug for benzodiazepines?

Answer 272

Flumazenil — benzodiazepine binding site antagonist (does not block barbituate function)

Question 273

Which benzodiazepines exert anticonvulsant effects without marked CNS depression?

Answer 273

Diazepam, lorazepam, clonazepam

Question 274

Which benzodiazepine gives you the most withdrawal effects?

Answer 274

Triazolam because it has a very short half-life

Question 275

Clinical uses for benzodiazepines

Answer 275

Anxiety, insomnia, seizures, muscle relaxation, alcohol withdrawal/detoxification, preanesthetic medication

Question 276

Non-benzodiazepine benzodiazepine receptor agonist

Answer 276

• Zolpidem (Ambien) • zaleplon (sonata) • Eszopiclone (Lunesta) — rapid onset, short, duration, slow tolerance development — used only for sleep, selectively bind the BZ1 subtype of GABA-A receptor — flumazenil also works against these drugs

Question 277

Buspirone

Answer 277

• selective anxiolytic effects : partial agonist at brain 5-HT1A receptors, also has an affinity for D2 receptors • affects, may take more than a week to become established— not used for panic disorder, used instead for generalized anxiety states

Question 278

Signs of stroke

Answer 278

BE FAST Balance Eyes- lost vision in one or both Face- uneven, drooping Arms- unilateral hanging limp Speech- trouble speaking Time- call 911 right away -- thrombolytics given 0-4.5 hrs post onset

Question 279

Classification of stroke

Answer 279

1.) ischemic: thrombotic (plaque) or embolic (clot) 2.) Hemorrhagic: subarachnoid (aneurysm burst) or intracerebral (torn artery)

Question 280

Uncommon causes of hemorrhagic stroke

Answer 280

- substance abuse, cocaine, amphetamines - thrombotic/hypercoagulable state such as pregnancy or cancer - Cerebral venous sinus thrombosis - inflammatory, vasculitis - infectious, endocarditis - trauma: dissection, fat emboli - Genetic: sickle cell - paradoxical, R-->L shunting

Question 281

Urgent labs to consider for stroke

Answer 281

- imaging, finger stick glucose, O2 sat - immediate: EKG, CBC, cardiac enzymes, BMP, INR, aPTT - Selected patients: LFTs, tox screen, BAL, preg test, ABG, CXR, LP, EEG, TT

Question 282

CT for stroke

Answer 282

- sensitivity increases after 24 hrs for stroke but may see signs 6 hrs post, checks for hemorrhage well - can be negative initially esp for ischemic stroke - FASTER, seconds - widely available

Question 283

MRI for stroke

Answer 283

- Contraindicated with metal-- pacemaker, replacement joint, etc - more expensive - slower, minutes - Can see much more clearly, can see ischemic strokes well

Question 284

How does TPA work? (tissue plasminogen activator)

Answer 284

Recombinant t-PA (from l-PA) binds to fibrin in thrombus and converts entrapped plasminogen into plasmin that initiates local fibrinolysis and causes degradation of the buildup

Question 285

Levels of stroke care from best to worst

Answer 285

1.) Comprehensive stroke center - less invasive procedures, better technology 2.) Thrombectomy-capable stroke center certification 3.) Primary stroke center - hospitalization and TPA 4.) acute stroke ready hospital- stabilize and transfer

Question 286

Neuronal damage of a stroke in 1 minute

Answer 286

- 1.9 million neurons - 13.8 billion synapses - 7 miles of axonal fibers -- 1 hour: neuronal loss equivalent to 3.6 years of normal aging

Question 287

MR CLEAN

Answer 287

Multicenter Randomized Clinical trial of Endovascular treatment of Acute ischemic stroke in the Netherlands

Question 288

ESCAPE

Answer 288

Endovascular treatment for Small Core and Proximal Occlusion ischemic stroke

Question 289

EXTEND IA

Answer 289

Extending the time for Thrombolysis in Emergency eurological Deficits- Intra-Arterial

Question 290

SWIFT PRIME

Answer 290

Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment

Question 291

REVASCAT

Answer 291

Randomized trial of Revascularization with Solitaire FR Device versus best medical therapy in the treatment of acute stroke due to anterior circulation of large vessel occlusion presenting within 8 hours of symptom onset

Question 292

Modified Rankin scale

Answer 292

- measure of primary outcomes following stroke intervention 0- No symptoms 1- no significant symptoms 2- slight disability, able to look after own affairs without assistance, but unable to carry out all previous activities 3- Moderate disability, requires help but walks unassisted 4- moderately severe disability- much assistance, cannot walk 5- severe disability- constant nursing care attention 6- Dead

Question 293

NASCAR

Answer 293

NeuroAngioSuite Cerebral Arterial Revascularization

Question 294

DAWN trial

Answer 294

206 patients with acute occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who were known to be well 6-24 hours earlier - showed thrombectomy + standard care produced better outcomes (thrombectomy 6-16 hours post symptom onset)

Question 295

In hospital management of stroke

Answer 295

- limit the size of the stroke - etiology - addressing all risk factors for secondary prevention - antiplatelets for anticoagulation - high intensity statin - BP management - normoglycemia, normothermia - A1C, lipid profile, ECHO-TTE, TEE, angiogram - DVT prophylaxis - Swallow fxn and speech therapy - occupational and physical therapy

Question 296

Risk factor modification for stroke

Answer 296

- HTN < 140/90 - DM A1C < 7 - abstinence of sympathomimetic abuse - Smoking cessation - EtOH goal <2 men, <1 women per day - Physical activity of 30 min per day - Afib- anticoagulation - ASA goal daily use if Framingham risk is >6%

Question 297

Ischemic stroke types

Answer 297

Large vessels: 1. anterior circulation, ICA, MCA, ACA 2. posterior circulation, vertebral artery, basilar artery, and branches Small vessels: 1. Penetrating arteries --> lacunar stroke

Question 298

Lacunar stroke

Answer 298

- HTN-induced endothelial damage - increased risk of bleeding with HTN - endothelial damage leads to clot formation Symptoms: - pure motor 33-50% (IC post limb, pons) - Pure sensory (thalamus, VPL nucleus) - Mixed motor sensory - Ataxic hemiparesis (IC, pons, corona radiata) - Dysarthria, clumsy hand syndrome (Pons, genu of IC)

Question 299

Results of anterior circulation stroke

Answer 299

Contralateral motor and sensory deficits - ACA: motor symptoms in the legs - MCA: motor symptoms in hands, and speech difficulty

Question 300

Results of posterior circulation stroke

Answer 300

- 20% of ischemic strokes - vertebral artery- cerebellar dysfxn - lateral medullary infarct- Wallenberg syndrome including vertigo, facial pain, dysphagia - Basilar artery- cranial nerve palsies

Question 301

Cortical stroke signs

Answer 301

1. Vision: field cut, loss of vision, double vision 2. aphasia/confusion: expressive, receptive, mixed 3. Neglect: gaze deviation, hemineglect

Question 302

How do we treat hemorrhagic strokes?

Answer 302

- Control BP if too high - reverse Anticoag if indicated - Monitor expectantly - hemorrhage CVAs tend to have more complications. Patients decompensate rapidly - Mannitol

Question 303

Risk factors for hemorrhagic stroke

Answer 303

- incidence: 25:100,000 - increasing age - Male - HTN - EtOH use - tobacco use - diabetes

Question 304

Putamen presentation of hemorrhagic stroke:

Answer 304

Contralateral hemiparesis, gaze paresis and aphasia or hemineglect

Question 305

Thalamus presentation of hemorrhagic stroke:

Answer 305

contralateral hemianesthesia

Question 306

Cerebellum presentation of hemorrhagic stroke:

Answer 306

vomiting, ataxia, nystagmus, facial paralysis, ipsi gaze palsies and LOC

Question 307

Pons presentation of hemorrhagic stroke:

Answer 307

coma, quadriplegia, pinpoint pupils, autonomic instability

Question 308

Types if intracranial bleeding

Answer 308

1. intracerebral parenchymal hemorrhage 2. subarachnoid hemorrhage 3. epidural and subdural hemorrhage 4. hemorrhagic conversion of ischemic strokes

Question 309

Modifiable risk factors for aneurysms

Answer 309

- smoking - HTN - heavy alcohol consumption - drugs- cocaine - OCP - atherosclerosis

Question 310

non-modifiable risk factors for aneurysms

Answer 310

- age - female - genetics/familial - collagen vascular diseases - arteriovenous malformations

Question 311

Types of aneurysms

Answer 311

1. saccular: bulging circle off of vasculature 2. fusiform: football shaped within vasculature 3. Dissecting: around a vasculature element

Question 312

Most common places for intracranial saccular aneurysms

Answer 312

- at the fork in the road 1. ACA 2. PCA 3. MCA 4. LCA bifurcation

Question 313

Aneurysm treatments

Answer 313

1. Conservative: risk factor management and serial imaging 2. Surgical clipping 3. coil procedure to prevent blood flow into the aneurysm

Question 314

Stroke clinical definition

Answer 314

acute onset of neurological deficit lasting more than 24 hours, less than 24 hours can be classified as a TIA

Question 315

Ischemic stroke (non-hemorrhagic, 85%)

Answer 315

- Large vessel: massive insult to main branch arteries, hemorrhage can occur on reperfusion - Types: 1. Global hypoperfusion: watershed or pseudolaminar infarct 2. Thrombotic: clot forms in situ blocking blood flow 3. Embolic: clot forms elsewhere, detaches and lodges in the brain artery often at branch points 4. Vasculitis -Small vessel: hypertensive arteriolar sclerosis and occlusion - Types: 1. Lacunar: deep brain, basal ganglia, IC, thalamus, pons

Question 316

Hemorrhagic stroke (15%)

Answer 316

- Small vessel: hypertensive - Types: 1. Slit hemorrhage 2. Massive HTN intraparenchymal hemorrhage - Vessel disease -Types: 1. Amyloid angiopathy- lobar hemorrhage 2. vascular malformation 3. aneurysm 4. vasculitis

Question 317

Tissue survival in a stroke depends on:

Answer 317

- presence of collateral tissue - duration of ischemia - magnitude and rapidity of reduced flow -- all of these determine location, and size of infarct and therefore clinical deficit resulting

Question 318

Global cerebral ischemia

Answer 318

- occurs when there is a generalized reduction of cerebral perfusion everywhere in the CNS resulting in diffuse ischemic/hypoxic encephalopathy - inciting events: Cardiac arrest, shock, severe prolonged hypotension -Clinical outcomes: 1. Mild/short: rarely irreversible damage (TIA) 2. Moderate: watershed infarct/laminar necrosis 3. Severe/long term: widespread neuronal death results, vegetative state, flat EEG, autolysis and liquefaction

Question 319

What is a watershed area?

Answer 319

- regions of the brain at the most distal reaches of the circulation, border between arterial territories, where middle of ACA and MCA is the greatest risk - necrosis begins here first - Usually seen after hypotensive episodes

Question 320

What are the most sensitive CNS neurons in ischemic stroke?

Answer 320

- pyramidal cells of the hippocampus (esp CA1/Sommers sector) - Cerebellar purkinje cells - pyramidal neurons of cerebral cortex (layers 3, 5, 6)

Question 321

Acute changes 6-24 hours post infarct

Answer 321

- Red neurons (eosinophilia, nuclear pyknosis--> karyorrhexis) - reactive glial changes

Question 322

Changes 24-48 hours post infarct

Answer 322

infiltration by neutrophils

Question 323

Subacute changes 48hours - 3 weeks post infarct

Answer 323

- tissue necrosis - liquefaction - Macrophage influx - 48-72 hrs, dominant cell for 2-3 wks - vascular proliferation starts at 1 week - reactive gliosis (brain scar-- acts like fibroblasts) by astrocytes at 1 week

Question 324

Changes greater than 2-3 weeks post infarct

Answer 324

- Removal of necrotic tissue- liquefaction - Loss of CNS architecture - Gliosis - Pia and arachnoid do not contribute to the healing process - healing progresses from edges --> center

Question 325

Earliest morphologic marker of neuronal death

Answer 325

- Red is dead (red neuron) - evident 6-12 hours after irreversible hypoxic/ischemic event - Cytoplasmic intense eosinophilia - cell shrinkage - nuclear pyknosis- chromatin condensation - loss of nucleolus and nissl substance

Question 326

Gliosis

Answer 326

- combined hyperplasia and hypertrophy of astrocytes, most important indicator of CNS injury - Gemistiocytic astrocyte - reactive - nuclear enlarge, chromatin becomes vesicular, prominent nucleolus forms, cytoplasm enlarges and becomes pink, thickens, GFAP stain shows star like shape

Question 327

Microglia reaction to injury

Answer 327

- CNS phagocytic cell- resident CNS macrophage - injury response: proliferate, develop elongated nuclei, aggregates around small foci necrosis (microglial nodules), congregate around dying neurons (neurophagia) - Reactive microglia- arrow - Astrocyte- arrowhead

Question 328

Acute ischemic injury 6-12 hours

Answer 328

- diffuse eosinophilia of neurons (red neurons) - Loss of nissl substance - Neurons also begins to shrink - Nuclear pyknosis and kayorrhexis - infiltration by neutrophils around 24 hrs after injury, lytic enzyme release

Question 329

Global ischemia diffuse acute morphology

Answer 329

- Diffuse swelling- edema increased weight (heavy) - widened and flattened gyri - narrowing of the sulci

Question 330

Global ischemia diffuse late morphology

Answer 330

- pseudolaminar necrosis - uneven loss of neurons with gliosis, layers 3, 5, and 6 most sensitive and lost - thinning of grey matter with layers

Question 331

Focal Cerebral Ischemia

Answer 331

- classic stroke, clinical deficits determined by the anatomic distribution of the infarction not underlying cause - neurologic symptoms develop rapidly over minutes - degree of slow improvement during period of months generally occurs - same lifestyle and genetic risk factors as CVD

Question 332

Embolism

Answer 332

- thromboembolism: larger, mural heart thrombus following MI - atheroembolus: smaller, atheromatous debris from carotid bifurcation - paradoxical embolism: lower extremity DVT through an ASD

Question 333

In situ thrombosis

Answer 333

- vasculitides (inflammatory vasculitis) - hypertensive arteriolosclerosis - occlusion, lacunar infarct

Question 334

What area is most affected by embolization?

Answer 334

- Middle cerebral artery-- direct extension of the internal carotid and 80% of blood flow. Right and Left equally affected

Question 335

What causes embolization?

Answer 335

- Cardiac mural thrombus from the left heart (MI, Afib) - Thromboemboli/atheroemboli from carotid bifurcation - Paradoxical emboli, from venous thromboemboli or right heart (children w heart malformations)

Question 336

Showered embolism is seen in what?

Answer 336

- bone fractures from massive trauma- bone marrow emboli - generalized dysfunction of cortical and cerebellar areas

Question 337

Focal cerebral ischemia- thrombotic occlusions

Answer 337

- most commonly associated with atherosclerosis and plaque rupture, and clot formation - Common sites: carotid bifurcation, MCA, basilar arteries

Question 338

Hemorrhagic infarct morphology

Answer 338

- similar to that described for non-hemorrhagic infarct with the addition of blood extravasation and resorption - anticoagulant drugs are a risk factor - venous infarct- superior sagittal sinus or deep cerebral veins - spinal cord infarct: traumatic interuption of feeding vessels from aorta

Question 339

Lacunar infarct

Answer 339

hypertensive arteriolar sclerosis of deep penetrating arteries that supply basal ganglia and brainstem, vessel wall thickens and lumen becomes occluded lenticular nucleus > thalamus > IC > deep white matter > caudate nucleus > pons

Question 340

Slit hemorrhage

Answer 340

rupture of small caliber penetrating artery resulting in a small slit-like blood filled space. hemorrhage resorbs leaning a small slit surrounding by brownish discoloration grossly

Question 341

Hypertensive encephalopathy

Answer 341

- clinical/pathological syndrome arising in the setting of malignant hypertension - characterized by cerebral dysfunction: HA, confusion, vomiting, convulsions sometimes leading to coma - rapid intervention needed to reduce the increased intracranial pressure

Question 342

Vascular dementia

Answer 342

- small bilateral infarcts over multiple years - grey matter: cortex, thalamus, basal ganglia - white matter: centrum semiovale - Symptoms: dementia, gait abnl, pseudobulbar signs with superimposed focal deficits

Question 343

Three types of underlying vascular disease that contribute to vascular dementia

Answer 343

1. cerebral arteriolar sclerosis from chronic hypertension 2. cerebral atherosclerosis 3. Vessel thrombosis or embolism from carotids or heart

Question 344

Ganglionic hemorrhage

Answer 344

Cerebrovascular intraparenchymal hemorrhage of the basal ganglia and thalamus from hypertension

Question 345

Lobar hemorrhage

Answer 345

Cerebrovascular intraparenchymal hemorrhage of the lobes of the cerebral hemispheres from cerebral amyloid angiopathy

Question 346

other contributing factors to Cerebrovascular intraparenchymal hemorrhage

Answer 346

- systemic coagulation disorders - neoplasms - vasculitis - aneurysms - vascular malformation

Question 347

What is the risk factor most associated with deep brain parenchymal hemorrhage?

Answer 347

Hypertension deep white/grey matter > brainstem > cerebellum

Question 348

Sign of Cerebrovascular intraparenchymal hemorrhage

Answer 348

Proliferative change and frank necrosis of arterioles

Question 349

What is the risk factor most commonly associated with cerebral lobar hemorrhages?

Answer 349

Cerebral Amyloid Angiopathy (CAA) - amyloidogenic peptides are deposited in walls of medium and small caliber meningeal and cortical vessels which weakens vessel walls - gene association: Apolipoprotein E gene, E2 or E4 associated with repeat bleeds

Question 350

What does cerebral amyloid angiopathy (CAA) look like?

Answer 350

- thickened vessel wall - IHC + for amyloid Abeta40 (turns brown) - leptomeningeal and cerebral cortical arteries typically involved - lobar hemorrhage - sometimes vessels in the molecular layer of the cerebellum - + congo red stain under polarized light - apple green color

Question 351

Where does hypertensive hemorrhage start in 50-60% of cases?

Answer 351

Putamen thalamus > pons > cerebellar hemispheres rarely

Question 352

The look of intraparenchymal hemorrhage at stages

Answer 352

Acute: blood extraversion and compression of adjacent brain tissue Old: cavitary destruction, rim of brownish color (hemosiderin) Early lesion: core of clotted blood with anoxic neuronal change in adjacent tissue with edema --> hemosiderin and lipid laden macrophages appear later on

Question 353

Acute clinical consequences of subarachnoid hemorrhage and ruptured aneurysm

Answer 353

- increased risk of additional ischemic injury from vasospasm - most significant with basilar SAH as major vessels can spasm

Question 354

Late clinical consequences of subarachnoid hemorrhage and ruptured aneurysm

Answer 354

- healing - fibrosis and scarring can obstruct CSF flow and the normal pathway of resorption

Question 355

What is the most common cause of a clinically signficant subarachnoid hemorrhage?

Answer 355

rupture of a saccular (berry) aneurysm in a cerebral artery

Question 356

4 groups of brain vascular malformations leading to intracranial hemorrhage

Answer 356

1. arteriovenous malformation* stroke risk 2. cavernous malformation* stroke risk 3. capillary telangiectasias 4. venous angiomas

Question 357

What areas of the brain are most vulnerable to damage?

Answer 357

Hippocampus, neocortex, cerebellum (large pyramidal neurons, purkinje cells)

Question 358

Where do the anterior and posterior circulations meet?

Answer 358

Circle of Willis

Question 359

The working brain consumes energy by:

Answer 359

1. maintenance of synaptic transmission 2. transport of sodium and potassium 3. preserving structural integrity

Question 360

energy metabolism during ischemia

Answer 360

decreased O2 and decreased glucose --> increased NADH, decreased ATP and KP, increased conc. lactate --> shortage of energy, acidosis

Question 361

Lipid metabolism of ischemia

Answer 361

increased Ca2+ --> activation of membrane phospholipase A2 --> release of poly-unsaturated fatty acids into intracellular compartment --> activation of phospholipase C --> arachidonic acid --> PGL, LT, TBX

Question 362

Consequences of brain ischemia

Answer 362

1. damage to membrane structure and function 2. dysfunction of receptors and ion channels 3. Free radical formation 4. inhibition of axonal transport, blebbing

Question 363

Ischemic penumbra

Answer 363

- ring-like area of reduced flow around an ischemic area where functional activity of the neurons is suppressed but structural integrity of the cells is maintained and can be reversible and viable - autoregulation of blood flow in the penumbra is disturbed, ATP normal, decrease in glucose amount

Question 364

Cerebral edema

Answer 364

- Excess accumulation of fluid in the intracellular or extracellular spaces of the brain - morphological changes: gyri are flattened, sulci are narrowed, and ventricular cavities become compressed - may lead to increased ICP and brain herniation --> respiratory arrest, cardiac arrect, and death

Question 365

Causes of cerebral edema

Answer 365

1. Ischemic strokes 2. Brain hemorrhages and strokes 3. TBI 4. infections: meningitis, encephalitis, Reye's, toxoplasmosis, subdural empyema 5. tumors 6. High altitudes: above 4900 feet: severe acute mountain sickness (AMS), high-altitude cerebral edema (HACE)

Question 366

Vasogenic cerebral edema

Answer 366

- due to a breakdown of the tight endothelial junctions that make up the BBB - resulting from trauma, tumors, inflammation, late stage cerebral ischemia, and HTN encephalopathy

Question 367

Hydrostatic cerebral edema

Answer 367

acute malignant hypertension: direct transmission of pressure to cerebral capillaries with transudation of fluid from the capillaries into the extravascular compartment

Question 368

Cerebral edema from brain cancer

Answer 368

Cancerous cells (glioma) of the brain can increase secretion of VEGF, which weakens the junctions of the BBB. Dexamethasone can be of benefit in reducing VEGF secretion

Question 369

High altitude cerebral edema (HACE)

Answer 369

capillary fluid leakage due to the effects of hypoxia on the mitochondria-rich endothelial cells of the BBB. immediately descend by 2000-4000 feet is a life saving measure

Question 370

Cytotoxic cerebral edema

Answer 370

- BBB intact, but a disruption in cellular metabolism impairs functioning of the sodium and potassium pump in the membrane, leading to cellular retention of Na and therefore water - seen in toxins such as: dinitrophenol, triethyltin, hexachlorophene, isoniazid

Question 371

Osmotic and Interstitial cerebral edema

Answer 371

- plasma dilution decreases serum osmolality resulting in a higher osmolality in the brain compared to the serum. This creates an abnl pressure gradient and movement of water into the brain, which can cause progressive cerebral edema - occurs due to a rupture of the CSF-BBB in obstructive hydrocephalus

Question 372

Brain herniation

Answer 372

- protrusion of brain tissue through one of the rigid intracranial barriers (tentorial notch, falx cerebri, foramen magnum) - Cingulate: subfalcine -- around the crista gali - Transcalvarial: through the skull - uncal: cortex under falx cerebelli - Transtentorial: upwardness of the cerebellum - tonsillar: dowardness of the cerebellum

Question 373

Cushing reflex

Answer 373

- systolic hypertension with increased pulse pressure, irregular respirations, and bradycardia - caused by significant increased ICP

Question 374

Treatments for Cerebral edema

Answer 374

- osmotherapy using mannitol or hypertonic soln - Diuretics (furosemide): to decrease fluid volume - Corticosteroids (dexamethasone) to suppress immune system and decrease brain inflammation - Hypothermia: lowering body temperature and reduce brain swelling - Ventriculostomy: to drain the blood from the ventricle - Surgical decompression

Question 375

Regrowth of axons in CNS or PNS

Answer 375

- reactivation of development - axon growth and guidance - synapse formation - activity-dependent competition

Question 376

Restoration of damaged neurons

Answer 376

- Glial overgrowth "scar" - recruitment of glia by inflammatory response - released cytokines suppress neural growth and synapse formation

Question 377

Genesis of new neurons

Answer 377

- neural stem cells - Strict rules: right place, right amount in order to become right neurons

Question 378

Peripheral nerve regeneration

Answer 378

-Henry Head's experiment: Precisely cut two nerves and recovered 1. Sensitivity to general pressure and touch 2. sensitivity to local stimuli - proved adult peripheral nerve regeneration

Question 379

molecular and cellular basis of peripheral nerve degeneration

Answer 379

1. injury to peripheral nerve 2. Macrophages rapidly remove myelin debris 3. expression of growth-related genes 4. Growth cone interacting with schwann cells, adhesion molecules on schwann cells for cone to attach and grow, axon growth promoting signals, neurotrophins, and ECM helping with growth, proliferating schwann cells promote axon regeneration

Question 380

Molecular mechs for regenerating peripheral nerves

Answer 380

- protein interactions are key: LRP4 and Agrin --> MuSK --> Rpsyn --> activate dystroglycan

Question 381

Damages to CNS

Answer 381

1. TBI: sports (Grimsley's brain), war 2. Hypoxia due to ischemia (Stroke) 3. Degeneration (alzheimer's, parkinson's)

Question 382

Limitations for regeneration in the CNS

Answer 382

1. Damage engages necrosis and apoptosis mechanisms 2. Damage does NOT reactivate developmental signaling 3. Damage upregulates growth-inhibiting chemorepellent factors Cytokine release --> inhibits Bcl2 --> Cytochrome C released from mitochondria --> activates Caspase 9 --> activates caspase 3 --> apoptosis and phagocytosis

Question 383

If a glial scar forms"

Answer 383

it inhibits the regrowth of the CNS neurons

Question 384

If a glial scar forms:

Answer 384

it inhibits the regrowth of the CNS neurons

Question 385

Inhibitory signals that limit axon growth in the CNS

Answer 385

MAG --> Lingo-1 Nogo-A --> NgR1, NgR2 OMgp --> PirB/LILRB2

Question 386

Where does neurogenesis occur in the adult mammalian brain?

Answer 386

1. olfactory bulb: granule and periglomerular cells 2. Hippocampus: granule cells

Question 387

Advantage of stem cells in adult neurogenesis and brain repair

Answer 387

- pluripotent which may be injected and form multiple types of cells for repair - Engineered to secrete needed factors for the regeneration process - Can be monitored for progression of the repair

Question 388

Three types of repair in the adult nervous system

Answer 388

1. regrowth of peripheral axons to reestablish sensory and motor synapses on muscles or other targets 2. Local sprouting of axons and dendrites at the damaged sites of the brain or spinal cord (impaired by death/extensive neuron damage, cytokine release causing inhibition, and glial scar formation) 3. ongoing generation in the brain (olfactory/hippocampus)

Question 389

Glasgow coma scale

Answer 389

Eyes: 1- does not open 2- opens to pain 3- open in response to voice 4- open spontaneously Verbal: 1- no sounds 2- incomprehensible sounds 3- incoherent words 4- confused, disoriented 5- oriented, converses normally Motor: 1- no movement 2- extension to pain (decerebrate) 3- abnl flexion to pain (decorticate) 4- flexion/withdrawal to painful stimuli 5- localizes to painful stimuli 6- obeys commands

Question 390

Opioid toxidrome

Answer 390

Recognition: miosis, bradycardia, bradypnea, hypotension, urine tox screen Management: Naloxone, Supportive- oxygen, BP stabilizers, consult poison control/pharmacy

Question 391

What two overdose drugs have the longest duration of action (therefore requiring more doses of naloxone)

Answer 391

- Methadone - Fentanyl - also morphine

Question 392

What causes a urine tox screen false positive?

Answer 392

- poppy seeds - prescription meds: verapamil, doxylamine, quetiapine, hydroxyzine - OTC: diphenhydramine - pts with lactic acidosis: diabetes, liver disease, other toxins ingested

Question 393

What causes a urine tox false negative?

Answer 393

- dilution with outside water source - substitution, someone else's urine - extra internal dilution, drinking excessive water or internet detox-kits - Rapid metabolizers

Question 394

Naloxone

Answer 394

- Sub-Q, IM, IV, or intranasal - Rapid action, short half-life, binds to opiate receptors - precipitates withdrawal symptoms - OTC

Question 395

Naltrexone

Answer 395

- oral - longer onset, longer half-life, and active metabolite - GI side effects, insomnia, mood issues - used to block cravings for opioid or alcohol

Question 396

Seizures

Answer 396

Temporary disruption of brain functioning resulting in abnormal, excessive neuronal activity Types: 1. Focal seizures: partial seizures, secondary generalized 2. Primary generalized: Grand mal, petit mal

Question 397

Epidemiology of seizures

Answer 397

- children and elderly most common - Causes: stroke, trauma, tumors, infections - Underlying cause: genetic, structural, metabolic - Positive signs: seeing flashes, arms jerking - Negative signs: impaired consciousness and self awareness, transient blindness, paralysis

Question 398

Temporal lobe seizures

Answer 398

- prolonged febrile convulsion - encephalitis

Question 399

Selective vulnerability for seizures

Answer 399

- hyperexcitability and excitotoxicity of the thalamus or hippocampus

Question 400

What types of genetics are involved in seizures?

Answer 400

- ion channels - synaptic transporters - DNA-binding proteins

Question 401

What conditions do you see with epilepsy?

Answer 401

1. Rett syndrome: mutant MeCP2 gene (methylation) --> altered gene expression --> abnl developments 2. Tuberous sclerosis complex: Cortical malformations, CNS maturation

Question 402

Field potential

Answer 402

Extracellular electrodes detecting synchronized actions of multiple neurons ( 100+ ms) measured with EEG in uV

Question 403

Action potential

Answer 403

Intracellular electrode detecting a signal action potential nerve firing (1-2 ms) measured in mV

Question 404

EEG cell contributions

Answer 404

Cortex strongest > deep structures such as hippocampus and thalamus

Question 405

EEG normal

Answer 405

- 1-30 Hz - 20-100 uV

Question 406

EEG alpha waves

Answer 406

- 8-13 Hz - relaxed wakefulness - parietal/occipital cortex

Question 407

EEG beta waves

Answer 407

- 13-30Hz - intense mental activity - frontal cortex

Question 408

EEG theta and delta waves

Answer 408

- 4-7 Hz theta - 0.5-4 Hz delta - drowsiness and early slow-wave sleep SWS

Question 409

What can sharp EEG spikes indicate?

Answer 409

The location of a seizure focus

Question 410

Focal seizures- partial

Answer 410

- originate from a small group of neurons - usually in the primary motor cortex: twitching of finger/ jerking of limb - limbic system alters behavior and consciousness

Question 411

Focal seizures: Secondary generalized

Answer 411

- starts in a focus, spread to both hemispheres - LOC, fall, rigidity (tonic), and jerking (clonic) phase - first symptom associated with the activity in the focus: twitch - preceded by auras

Question 412

Neural activity at focus of seizure

Answer 412

- synchronized response of small group neurons - Paroxysmal depolarizing shift (PDS) - sudden large (20-40mV), long (50-200ms) depolarizations --> train of action potentials lead to an "after-hyperpolarization" and stabilization

Question 413

Neural mech of depolarizing phase

Answer 413

- activation of Glut channels (AMPA and NMDA receptors) and voltage-gated ion channels - NMDA receptor enhances excitability by relieving Mg2+ blockage on AMPA receptors during depolarization --> extra Ca2+ entry --> more APs

Question 414

Surround inhibiton

Answer 414

- increase focal activity --> interictal spike - confined by after-hyperpolarization - Ca2+ activated K+ channels and GABA released from interneurons (inhibitory x2)

Question 415

How does surround inhibiton cause seizures?

Answer 415

- failure of surround inhibition and GABA release - no after-hyperpolarization --> continuous high frequency action potentials --> synchronization of neighbors --> seizure spreads

Question 416

What breaks surround inhibition?

Answer 416

- GABAergic transmission is labile, intense discharges result in failed GABA response - Depletion of readily releasable pool of GABA - Changes in gene expressivity or sensitivity of channels

Question 417

How does seizure activity spread?

Answer 417

- through existing circuits: thalamocortical, subcortical, transcallosal --> distant neurons --> project back to the focus (BACK-PROPAGATION) - both hemispheres: secondary generalized seizures --> LOC

Question 418

What terminates a seizure?

Answer 418

- after-hyperpolarization reappearing and GABA inhibition is restored - Symptoms: post-ictal, confusion, drowsiness, focal deficits

Question 419

Primary generalized seizures

Answer 419

- not preceded by aura or focal seizure - involve both hemispheres simultaneously - driven by THALAMO-CORTICAL circuits - Grand mal and petit mal (absence)

Question 420

Grand mal vs petite mal

Answer 420

Grand mal: Convulsive, tonic-clonic seizure that begins abruptly --> fall/rigidity --> incontinence --> cyanosis - tonic phase: 30 sec --> clonic jerking 1-2 min --> sleepiness, HA Petit mal: non-convulsive, seen in children frequently. 10 seconds, LOC but not posture (trance-like) and not followed by confusion

Question 421

Absence seizure

Answer 421

- childhood: 3-Hz spike-wave for 10-30 seconds, rhythmic sleeping activity - rapid generalization in the upper brain stem or thalamus--> projects diffusely to cortex - preceded and followed by normal background activity

Question 422

Propagation of primary generalized seizures

Answer 422

increase thalamus activity --> synchronization --> cortical hyperexcitability --> feedback --> GABAergic inhibition --> hyperpolarize for 200mn after each burst --> inhibition -- differs from focal seizures by preserved GABAergic inhibition. Depolarization depends on AMPA channels and Transient-type Ca2+ channels in thalamic relay nuclei

Question 423

Facilitation of generalized seizure activity

Answer 423

interneuron hyperpolarize relay neurons --> activate T-type Ca2+ channels in relay neuron --> rebound firing --> stimulation of GABA neurons --> repeat -- relay neurons also excite cortical neurons in the same rhythmic, oscillatory pattern

Question 424

Seizure triggers

Answer 424

- stress and sleep loss - sensory stimuli (flashing lights) - circadian rhythms and hormonal patterns

Question 425

Focal epilepsy is highly localized in:

Answer 425

Temporal lobe, hippocampus -- unilateral shrinking or hippocampus + dilation of temporal horn

Question 426

PET imaging for seizures

Answer 426

- increased metabolic demand - decreased O2, ATP - increased lactate - the brain increases blood flow to compensate but the need to restore large ion shifts takes a lot of energy - interictal hypometabolism in the focus of the seizure

Question 427

Systemic deificits of repeated seizures

Answer 427

- hypoxia, hypotension, hypoglycemia, acidemia, decreased ATP Complications: cardiac arrhythmias, pulmonary edema, hyperthermia, and muscle breakdown

Question 428

Status epilepticus

Answer 428

repeated generalized seizures without full consciousness. 30+ minutes of convulsive seizures may lead to brain injury and death

Question 429

Excitotoxicity

Answer 429

- immature brains: ineffective K+ buffering by glia, decreased glucose transport - loss of pyramidal neurons of hippocampus - excess Glu release --> neuronal damage - increased intracellular calcium --> activate Ca-dependent enzymes (phosphatases like calcineurin, and proteases like calpains, and lipases) -domoic acid toxicity

Question 430

Domoic acid toxicity

Answer 430

- glutamate analog found in algae, and shellfish leading to severe seizures and amnesia, direct effects on hippocampus

Question 431

Surgical resection for seizures

Answer 431

- removal of temporal lobe in hippocampal seizures for drug-resistant epilepsy -SE: memory loss, social problems

Question 432

When to refer a veteran from primary care

Answer 432

Primary care: screening for MH conditions. initiation of pharmacological treatment for mild/moderate symptoms, co-management PC-MHI: Mild/moderate mental health conditions, follow-up care post initial screening, behavioral interventions for chronic problems Specialty mental health: Specialty treatment of PTSD, severe depression/anxiety, serious mental illness, substance dependence treatment, inpatient psychiatric care

Question 433

Examples of evidence based psychological treatment

Answer 433

-CBT for the treatment of insomnia - mindfulness - Exposure therapy -

Question 434

Exposure therapy

Answer 434

- most effective for PHOBIAS, also for OCD, PTSD, panic disorder, and GAD - hierarchal approach: 1. interoceptive exposure 2. imaginal exposure 3. in-vivo exposure

Question 435

Division of the VA

Answer 435

- Veterans integrated service network (VISN) - Veteran Health Administration (VHA) - IHS reimbursement for AI/AN

Question 436

Principle of antiseizure drugs

Answer 436

- decreases excitatory Glu transmission - increase inhibitory GABA transmission

Question 437

Side effects of antiseizure drugs

Answer 437

- sedation, drowsiness, ataxia, diplopia - Stevens-Johnson syndrome - Liver toxicity - Cytochrome p450 induction - teratogen (cleft palate, facial dysmorphia, lower IQs)

Question 438

Phenytoin

Answer 438

- Blocks voltage gated Na+ channels - also alters K+ and Ca2+ conductance, membrane potentials, etc - Seizure types used for: Partial (focal), generalized tonic-clonic, status epilepticus prophylaxis - zero-order kinetics - cytochrome P-450 induction - sedative only at higher doses

Question 439

Phenytoin and zero order kinetics

Answer 439

- CYP2C9 and CYP2C19 fully saturated at therapeutic concentrations , DDIs - clearance independent of concentration - small dose increase can lead to a large increase in drug in the body - other SEs: nystagmus, hirsutism, gingival hyperplasia

Question 440

Carbamazepine

Answer 440

- Blocks voltage-gated Na+ channels - seizure types used for: Partial (focal), Generalized tonic-clonic - CYP 450 induction - non-sedative

Question 441

Lamotrigine

Answer 441

- blocks voltage-gated Na+ channels - inhibits VG Ca2+ channels (absence seizure help) - seizures used for: Partial (focal), generalized tonic-clonic, absence seizures in children - non-sedative, yes drowsiness

Question 442

Sedation vs drowsiness

Answer 442

Sedation: slower reaction times and impaired performance in activities that require diligent attention Drowsiness: subjective feeling of being tired

Question 443

Topiramate

Answer 443

- Blocks voltage-gates Na+ channels - potentiates GABA, possible antagonist of AMPA - Seizures used for: partial (focal), Generalized tonic-clonic - sedative, cognitive slowing

Question 444

Gabapentin

Answer 444

- Blocks voltage-gates Ca2+ channels - inhibits trafficking of N-type channel subunit from the cytoplasm--> membrane - seizure types used for: Partial (focal), generalized tonic-clonic - sedation and/or drowsiness

Question 445

Ethosuximide

Answer 445

- Blocks voltage gates Ca2+ channels - Specifically low traffic T-type channels in the thalamus (responsible for generating rhythmic cortical discharge in absence) - Seizures used for: Absence (first line) - non-sedative - Transient fatigue/lethargy - gastric distress is common (pain, nausea, vomiting)

Question 446

Levetiracetam

Answer 446

- Binds synaptic vesicle proteins SV2A (poorly understood) - Seizures used for (adjunctive): partial (focal), generalized tonic-clonic - non-sedative, yes drowsiness

Question 447

Valproic acid

Answer 447

- Blocks voltage-gated Na+ channels - blockade of NMDA receptor mediated excitation - increases synaptic GABA levels by: increasing production, inhibiting reuptake by GAT-1, and inhibits degradation by GABA transaminase/ GABA-T -Seizures used for: partial (focal), generalized tonic-clonic, absence (preferred to ethosuximide if pt has concomitant tonic-clonic) - non-sedative, GI distress common, hepatotoxicity esp under 2 or if already taking many other drugs

Question 448

Phenobarbital

Answer 448

- Allosteric modulator of GABAA receptors to potentiate GABA activity - Seizures used for: Partial (focal), generalized tonic-clonic - sedative - CYP450 induction

Question 449

Benzodiazepines

Answer 449

- Allosteric modulator of GABAA receptors to potentiate GABA activity - Seizures used for: Acute status epilepticus, Diazepam given IV or rectally - acute use only - Sedative

Question 450

Tiagabine

Answer 450

- Inhibits GABA reuptake by GAT-1 (esp in forebrain, hippocampus) - Seizures used for (adjunctive): Partial (focal) - non-sedative, yes drowsiness - difficulty concentrating, confusion

Question 451

Vigabatrin

Answer 451

- Inhibitor of GABA transaminase (GABA-T) irreversibly - seizures used for: partial (focal) refractory to other treatments - non-sedative, yes drowsiness - long-term use associated with peripheral visual field defects in 30=50% of patients

Question 452

Diffuse global ischemia

Answer 452

Thinning of grey matter and preservation of white matter. Pseudolaminar necrosis of grey matter looking like stripes