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Neuro > Unit 2 > Flashcards

Unit 2 Flashcards

1
Q

Identify neurons and all types of glial cells, their normal functions, and their reactions to injury

A
  • types of glial cells: astrocyte, oligodendrocyte, ependymal cell, microglia cell
  • “matrix” of grey matter is called neuropil and is made of processes of neurons and glial cells and has blood vessels dispersed within it
  • subarachnoid space dips into CNS around leptomeningeal vessels to form perivascular space
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2
Q

Discuss the significance of the RER/Nissl substance and how it reacts to axotomy

A
  • large round nucleus
  • prominent nucleolus due to high protein demand
  • Nissl substances stain basophilic in H&E to reflect protein synth
  • in axotomy (transection of axon), RER disaggregates and neuronal cell body swells –> cytoplasm is smooth and nucleus is displaced towards the periphery of cell –> chromatolysis
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3
Q

ID the basic components of the neuronal cytoskeleton and how alterations of some of these components are associated with neurodegenerative diseases

A
  • cell body contains neurofilaments and neurotubules (alpha and beta tubulin) which form a lattice cytoskeleton that supports axon
  • cross bridges of tau protein and microtubule associated proteins link neurotubules to each other
  • in alzheimer’s: abnormal filaments appear and form neurofibrillary tangles
  • dead/dying neurons are called “red cell” and shrink, become eosinophilic (due to condensation of mitochondria) and nucleus becomes pyknotic
  • neuronal storage diseases accumulate materials if deficiency in lysosomal enzymes
  • axonal alterations in Wallerian degen
  • neuritic plaques in alzheimer’s disease: amyloid accumulates in brain
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4
Q

Discuss the uses of silver stains in the histological study of the CNS

A
  • H&E does not stain neuronal processes
  • ammoniacal silver deposits into cytoskeleton
  • commonly used is Bielschowsky stain
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5
Q

Recognize that GFAP is a key protein of astrocytes

A
  • astrocytes have intermediate filaments made of glial fibrillary acidic protein (GFAP)
  • Abs against GFAP are used to find reactive and neoplastic astrocytes
  • rosenthal fibers are in astrocytic processes and contan GFAP
  • mutations of GFAP lead to Alexander disease –> diffuse deposition of Rosenthal fibers –> white matter degen and neurological dysfunction
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6
Q

Describe how myelin is formed and what cells make myelin in the CNS and PNS

A
  • oligodendrocytes in CNS

- Schwann cells in PNS

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7
Q

Describe the role of microglia in CNS inflammation and repair

A
  • phagocytic system in brain
  • after injury, migrate to lesion, mitosis, engulf foreign material
  • receptors that sense damaged tissue, viruses, and other toxins
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8
Q

Describe the structure of the sarcolemma and key intracellular, transmembrane, and extracellular proteins associated with it, and how they are involved in the pathogenesis of muscular dystrophies

A
  • myofibers are bound to ECM by proteins: dystrophin and DAC
  • dystrophin is under sarcolemma and attaches to cytoskeletal actin
  • DAC made of dystroglycans and sarcoglycans
  • dystrophin is bound to beta dystroglycan
  • dystroglycan is bound to merosin
  • mutatons in dystrophin –> DMD and becker’s
  • defect in sarcoglycan cause limb girdle dystrophies
  • deficiency in merosin is found in congenital muscular dystrophies
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9
Q

Describe how type I and type II fibers are distributed in normal muscle and in the denervation atrophy

A
  • type 1 are slow and red
  • type 2 are fast and white
  • in mammals, type 1 and type 2 fibers are present in all muscles but proportion differs in different muscles
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10
Q

Compare and contrast the differences between central and peripheral myelin

A
  • axons >1micron are myelinated in CNS and PNS
  • CNS: myelin is produced by oligodendrocytes; each cell wraps around many axons
  • ## PNS: myelin is produced by schwann cells; only makes one segment of myelin –> more efficient regen
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11
Q

Describe the pathogenesis and pathological process of Wallerian degeneration and segmental demyelination. Which is faster?

A

Wallerian degen:

  • neuron cell body maintains azon through axoplasmic flow and chromatolysis to make more protein to regen axon
  • regen depends on how well cut ends are put together –> bad = collagen, schwann cell processes, and axonal sprouts

segmental myelination:

  • breakdown and loss of myelin over a few segments
  • axon is intact and there is no change in cell body
  • dec conduction velocity
  • schwann cells make new myelin
  • demyelinated axons, thin myelin, onion bulbs (concentric Schwann cell processes and collagen)
  • occurs in inflammatory demyelinative neuropathies and CMT
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12
Q

Define concussion or mild traumatic brain injury

A

temporary (or not) unconsciousness caused by a blow to the head

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13
Q

ID the peak age groups in which head injuries occur and the mechanisms whereby these injuries are received

A
  • peak age is 24-35, but also for 0-4yo and >65yo

- traffic, transport, assaults, homicides, suicides, falls

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14
Q

Discuss the pathophysiology of various types of head injury and how they occur

A

Skull fractures:

  • contact
  • linear: ID through xray
  • depressed: bone fragments pushed down maybe into brain
  • basilar: high velocity; CSF leaks
  • diastatic: separation of skull at suture lines
  • growing: infancy; dural tears and herniation of arachnoid

Epidural Hematoma:

  • intracranial, extradural arterial bleeding
  • shearing of middle meningeal artery
  • lucid interval

Subdural hematoma:

  • translational accel
  • rupture of bridging veins that connect brain with sagittal sinus

Cerebral contusion:

  • superficial hemorrhagic contusions of brain
  • hemorrhage –> herniation
  • prevent brain swelling and evacuate large hematomas

Diffuse axonal injury:

  • rotational accel injury
  • shearing of axons –> retraction balls
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15
Q

Recognize the goal of treatment in head injuries

A
  • prevent brain swelling, inc ICP, further hypoxia, dysautoreg, and herniation
  • primary injury is usually irreversible; secondary is due to after effects and preventable
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16
Q

Discuss the reason for the control of intracranial pressure in the treatment of head injury

A
  • brain is non compressible so if mass keeps getting bigger, you inc ICP and at some point the brain will herniate
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17
Q

Recognize the signs and symptoms of increased intracranial pressure. Understand the clinical and pathologic features of the 4 herniation syndromes presented here

A
  • trauma, ischemia, neoplasm, infection, and hydrocephalus can cause mass effect

herniation syndromes:
- all share symptoms of lethargy and poor responsiveness –> sign of inc in ICP

1) subfalcine:
- cingulate gyrus pushed away from expanding mass –> herniates below falx cerebri
- kink in ACA –> may lead to stroke here

2) transtentorial (uncal):
- uncus of medial temporal lobe) herniates across tentorial edge and into posterior fossa
- compresses midbrain and cerebral peduncle –> ipsilateral 3rd nerve palsy and contralateral hemiparesis
- hemorrhage in BS

3) central herniation:
- downward pressure centrally –> bilateral uncal herniation

4) tonsilar herniation:
- cerebellar tonsils herniate downward into foramen magnum
- compress medulla –> CV and resp changes and Cushing’s

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18
Q

Recognize the Glasgow Coma Scale, its utility in predicting injury severity and outcome, and the elements of the clinical evaluation of concussion

A
  • looks at eye opening, best motor response, and verbal response
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19
Q

List 5 of the most common symptoms of concussion

A
  • confusion and amnesia
    1) headache
    2) dizziness
    3) poor attention
    4) inability to concentrate
    5) memory problems
    6) fatigue
    7) irritability
    8) depressed mood
    9) intolerance of bright light
    10) sleep problems
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20
Q

Should you do a lumbar puncture with an intracranial mass lesion?

A

NO

- will precipitate a herniation syndrome because of differential pressures between cranial and spinal subarachnoid space

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21
Q

Describe the pathophysiology of traumatic brain injury

A
  • mechanical forces –> massive depol –> excitotoxicity of neurons due to overactivation of receptors for glutamate –> Ca influx into cells –> lots of enzymes activated –> damage cell structures and BBB –> vasogenic edema
  • spike in extracellular K –> glutamate transporter (Na+Glu K) reverses and Glu can’t be cleared –> influx of K –> cell swells –> cytotoxic edema
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22
Q

What is the treatment for inc ICP?

A
  • manipulate intravascular space, brain parenchyma, and cerebrospinal fluid space
  • ABCs of life support
  • give O2 –> dec blood volume due to vasoconstriction
  • osmotic diuretics (mannitol)
  • ventricular catheters to drain CSF space
  • drug induced coma with barbiturates dec metabolic demand
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23
Q

Recognize the general presentation of a large vessel or small vessel ischemic stroke and TIA

A

Large vessel:
- deficits in multiple systems (e.g. hemiparesis, hemisensory loss, hemianopsia)

Small vessel:

  • isolated motor/sensory deficit on one side of the body
  • occlusion of small penetrating vessels
  • lacunar infarcts –> multinfarct dementia

TIA:
- neuro deficits disappear by 24hrs

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24
Q

Discuss the non-atherosclerotic causes of stroke in a young patient

A

Vasculopathies: non inflam hyperplasia of arteries

    • fibromuscular dysplasia: women in 30s; media hypertrophy –> stenosis; renal artery; arterial dissection and intracranial saccular aneurysms
    • moya moya: focal occlusion of MCA; intimal hyperplasia;
    • spont arterial dissection: tear in endo of artery –> dissection –> emboli; treat with anticoag or surgery

Hematological Disorders:

  • factor deficiencies
  • malignancies
  • sickle cell anemia
  • hyperviscosity states
  • oral contraceptives
  • antiphospholipid antibodies

Inflam mech:

  • vasculitis
  • migraine (vasospasm)

Venous Infarction:
- dehydration, CNS infections, hypercoag states

Vasospasm:
- symp drugs; HTN; vessel irritation

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25
Q

Intraparenchymal hemorrhage

A
  • formed blood clots which dissect into brain
  • often due to HTN and age
  • typically in basal ganglia, thalamus, pons, and cerebellar deep grey matter
  • amyloid angiopathy –> recurrent lobar hem –> dementia and disability
  • mild headache, deficit, nausea –> progress rapidly
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26
Q

Intraventricular hemorrhage

A
  • hemorrhage that finds its way into the ventricular system

- rarely in isolation

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27
Q

Hemorrhagic transformation

A
  • large vessel cortical strokes

- asymptomatic if mild bruising or fatal if large hematoma

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28
Q

Clinical presentation of hemorrhages

A
  • sudden onset of neuro deficits

- headache, nausea, vomiting, dec consciousness

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29
Q

Treatment of hemorrhage

A
  • prevent with control of BP
  • smoking cessation
  • anti-platelet or anticoagulants
  • ICP monitoring device or drainage
  • treat with nimodipine or statins to reduce ischemic damage from vasospasm
  • surgical fix of bleeding source
  • do not over anticoagulate
  • helmets
  • suspect aneurysms
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30
Q

Discuss the importance of mechanism of stroke in both resuscitation and prevention

A

1) minimize worsening of initial event
2) understand event to prevent further events
3) evaluated for rehab
4) risk factors addressed

  • for ischemic stroke: get history, physical exam, CT, EKG, and blood tests
  • echo if cardiac embolus is likely
  • small vessel: no further testing usually
  • single event in large vessel or embolic pattern and afib on ECG: no further testing
  • LP to exclude neurosyphilis, vasculitis, and other inflam conditions, but not routine part of ischemic stroke, but helps in determining sucarachnoid hemorrhage
    \
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31
Q

Discuss the basic principles of emergency treatment of ischemic stroke or hemorrhage

A
  • give thrombolytic agents (TPA) within 4.5hrs
  • keep fluids up, max CO, and resist lowering BP
  • be careful of saline and water but give if dehydrated
  • TPA contraind if abnormal CT and stroke has progressed past recovery, severte HTN, coag problems, or coma
  • ## give glucose only when hypoglycemia exists
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32
Q

Define the syndrome of delirium

A
  • a rapidly developing disorder of attention characterized by an inability to maintain a coherent line of thought
  • commonly underaroused, lethargic, and somnolent
  • toxic and metabolic causes are common
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33
Q

Discuss the common etiologies and evaluation of delirium

A
  • common in hospitalized patients
  • perturbations in metabolic environment of brain
  • cholinergic, dopaminergic, histaminergic, noradrenergic, and serotonergic neurons are vulnerable
  • usually ok if fix insult within a few days
  • drugs and toxins
  • metabolic disorders
  • infection and inflammatory disease
  • evaluate with history, PE, and neuro exam –> metabolic panel, CBC, urinalysis, utox, ECG, CT/MRI
  • get LP if suspect brain infection
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34
Q

Define the syndrome of dementia

A
  • acquired and persistent impairment in intellectual function with deficits in 3 of memory, language, visuospatial, emotion/personality, and complex cognition
  • interferes with social and occupational activities
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35
Q

Discuss the common etiologies and evaluation of dementia

A
  • reversible and irreversible causes

reversible (15%):

  • drug/toxins
  • mass lesions
  • hypothyroidism
  • vitB12 def
  • neurosyphilis
  • inflam disease
  • systemic inflam
  • severe depression
  • mild traumatic brain injury

irreversible (85%)

  • AD
  • FTD
  • vascular dementia
  • huntingtons
  • parkinsons
  • lewy body
  • CJD
  • MS
  • HIV assoc dementia
  • severe traumatic brain injury
  • evaluate: important to look for reversible causes
  • history, PE, CMP, CBC, TSH, B12, RPR, CT/MRI scan
  • LP, EEG, HIV, ESR, Abs for AI disease, Wilson’s, heavy metals, genetic testing, angiography, brain biopsy
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36
Q

Understand the principles guiding treatment of delirium and dementia

A

Treatment of delirium:

  • ID and correct cause quickly
  • change environment: clock, calendar, sleep, etc.

Treatment of dementia:

  • avoid drugs that worsen mental status (benzos, antichol drugs)
  • low dose atypical antipsychotics
  • antidepressant (SSRI) treatment if depression is significant
  • informed counseling
  • treat AD with AChEIs (donepezil) and memantine (NMDA antagonist)
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37
Q

Compare delirium and dementia

A

Delirium

  • acute
  • fluctuating consc
  • impaired attention
  • poor memory
  • incoherent speech
  • usual toxic and metabolic causes
  • usually reversible

Dementia

  • chronic
  • normal consc
  • normal attention
  • amnesia
  • aphasia
  • rarely toxic/metabolic
  • usually irreversible
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38
Q

Describe Alzheimer’s disease

A

Clinical features:

  • early memory and visuospatial problems
  • age-related
  • stage 1: amnesia is most notable, stage 2: dementia is notable, stage 3: severe mental and physical incapacity
  • mild cognitive impairment is a transitional stage between normal aging and AD

Neuropath:

  • cerebral atrophy
  • amyloid plaques and neurofibrillary tangles
  • diagnosis of definite AD is from brain biopsy (rare) or autopsy
  • typically found in cortex and hippocampus

Etiology:

  • genetic and environmental factors
  • trisomy 21 related
  • APP gene on chr21, presen1 on chr14, presen2 on chr1, E4 allele of APOE
  • generally unknown
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39
Q

What is the Cholinergic Hypothesis?

A
  • ACh is deficient in AD –> loss of cholinergic cells in basal forebrain is correlated with cognitive impairments in AD
  • donepezil and other AChEIs have been approved for AD
  • memantine an NMDA antagonist helps in AD
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40
Q

Describe Frontotemporal dementia

A
  • early behavioral, executive, and language problems
  • changes in behavior and comportment, but not really memory
  • degen disease of frontal and temporal lobes
  • disinhibition, apathy, and exec dysfcn
  • early involvement of frontal and temporal lobes but late sparing of hippocampus
  • serotonergic dysfunction
  • NF tangles
  • ubiquitin inclusions, tau reactive intraneuronal inclusion, CDP-43 deposition
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41
Q

Describe Parkinson’s disease

A
  • resting tremor, bradykinesia, rigidity, and postural instability
  • lewy bodies in substantia nigra
  • dopamine deficiency
  • standard PD drugs and AChEI help
  • lewy body dementia is related (dementia, parkinsonism, visual hallucinations, fluctuating consc)
  • see disturbances of synculein
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42
Q

Describe Huntington’s disease

A
  • AD disease with dementia and chorea
  • personality changes
  • caudate atrophy
  • CAG genetic testing
  • neuroleptic drugs and tetrabenazine can help for chorea
  • look at pattern of atrophy
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43
Q

Describe Binswanger’s disease

A
  • vascular dementia due to long standing HTN –> ischemia –> lacunar infarction
  • slowly progressive
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44
Q

Describe Normal Pressure Hydrocephalus

A
  • reversible
  • dementia, gait, urinary incontinence, enlarged ventricles with normal sulci on imaging –> hydrocephalus
  • CSF pressure may increase at night
  • if respond to large volume spinal tap –> can try for ventricular or lumbar shunt
  • rare
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45
Q

Describe Multi-Infarct Dementia

A
  • vascular dementia
  • repeated strokes erode cognitive fcn –> brain tissue destroyed –> dementia
  • large vessel or small vessel
  • stepwise deterioration
  • best treatment is prevention of strokes
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46
Q

Describe CJD

A
  • rare, but rapidly progressive and always fatal and transmissible
  • prion (proteinaceous infectious particle) disease –> conformational change
  • 90% of cases are sporadic but have been transmitted
  • present with dementia that progresses over weeks to months
  • confusion, psychosis, myoclonus, periodic EEG, cortical or subcortical hyperintensities on MRI
  • death w/in 4-12mos
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47
Q

Describe Progressive supranuclear palsy

A
  • bradykinesia
  • rigidity
  • falls
  • abnormal vertical eye movements
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48
Q

Describe amyotrophic lateral sclerosis

A
  • weakness and atrophy
  • fasciculations
  • UMN and LMN signs
  • spontaneous death of neuronal populations involved in motor neurons in spinal cord
  • disturbance of ubiquitin
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49
Q

Recognize the WHO grading system for selected examples of primary CNS neoplasms

A

1 (least aggressive) to 4 (most aggressive)

based off of histologic origin

1) tumors with low proliferative potential and possibility of cure following surgical resection alone
2) generally infiltrative; low proliferation; tend to progress to higher grade; treat with watchful waiting of irradiation
3) evidence of malignancy; nuclear atypia and mitotic activity; treat with adjuvant radiation and/or chemo
4) cytologically malignany; mitotically active; necrosis prone; rapid pre and postop disease evolution and fatal outcome

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50
Q

Compare and contrast the WHO grade 1 tumor that is usually amenable to cure by surgical resection alone, versus the diffuse astrocytomas and oligodendrogliomas, grades 2-4, that are NOT curable by resection alone

A

a

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51
Q

Discuss how histological typing and grading of these tumors correlates strongly with prognosis and affects treatment

A

a

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52
Q

Identify which tumor type(s) tends to spread throughout the CSF axis

A

a

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53
Q

Describe Ganglioglioma

A
  • grade 1
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54
Q

Describe Ganglioglioma

A
  • grade 1
  • usually in temporal lobe
  • cystic
  • well demarcated
  • calcified
  • diagnosis based on histo features of lesion
  • jumbled, cytologically abnormal neurons in a low grade glial background
  • microcysts with mucin
  • BRAF V600E gene
  • treat with surgical excision
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55
Q

Describe choroid plexus papilloma

A
  • grade 1
  • intraventricular
  • more abundant papillary formations
  • in children occur in lateral ventricles
  • in adults occurs in 4th ventricle
  • low mitotic rate and mild nuclear atypia
  • treat with surgical excision
  • block CSF flow and produce hydrocephalus
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56
Q

Describe diffuse astrocytoma

A
  • grade 2
  • arise in white matter in 30-50yo
  • blurred boundaries
  • rarely can be excised but can be debulked
  • lots of fibrillary astrocytes
  • mild hypercellularity
  • mild nuclear pleomorphism
  • irregular dist of tumor astrocytes
  • mitotic activity
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57
Q

Describe oligodendroglioma

A
  • grade 2
  • mostly in adults
  • white matter but infiltrate cortex
  • seizures
  • calcified tumors
  • round monotonous nuclei with little cytoplasm –> fried egg appearance
  • low mitotic activity
  • not curable with resection alone
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58
Q

Describe ependymoma

A
  • usually present before 20s
  • usually 4th ventricle
  • obstructive hydrocephalus
  • calcified tumors
  • protrude from 4th ventricle
  • well demarcated
  • ## formation of perivascular psudorosettes (perpendicular cells around blood vessels)
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59
Q

Describe anaplastic astrocytoma

A
  • grade 3
  • inc mitotic rate
  • MIB1 nuclear labeling indices
  • does not show histo features of necrosis or microvascular prolif
  • crowded tumor cells
  • nuclear hyperchromatism and variation in shape and size
  • tumor cell growth rate correlates with prognosis strongly
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60
Q

Describe anaplastic oligodendroglioma

A
  • grade 3
  • round, uniform nuclear features
  • scant cytoplasm
  • fried egg appearance
  • microvascular prolif
  • more mitotic activity
  • higher MIB1 labeling index
  • prognosis related to genetic signature: LOH1p19q = better prognosis than without
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61
Q

Describe anaplastic ependymoma

A
  • grade 3
  • more mitotically active
  • usually childhood and 4th ventricle
  • histo =/= prognosis
  • recurs over several years due to CSF dissemination
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62
Q

Describle glioblastoma

A
  • grade 4
  • most common of all gliomas
  • synonymous with astrocytoma
  • most malignant
  • usually de novo instead of due to progression (primary)
  • 50-60yo and peds
  • multifocal origins
  • not surgically curable but try to debulk
  • less than 1yr survival
  • diagnose with: nuclear abnormalities, mitotic activity, microvascular, proliferation necrosis
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63
Q

What does a BRAF fusion lead to?

A
  • grade 1 pilocytic astrocytoma
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64
Q

What can and IDH mutation lead to?

A

1p/19q co deletion –> oligodendroglioma –> anaplastic oligodendroglioma

1p/19q codeletion or TP53 mutation/17p loss –> oligoastrocytoma –> anaplastic oligoastrocytoma

TP53 mutation/17p loss –> difuse astrocytoma –> anaplastic astrocytoma –> secondary GBM

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65
Q

How does primary GBM occur?

A

10q loss, PTEN mut, EGFR amp, CDKN2A/B del –> primary GBM

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66
Q

Describe medulloblastoma

A
  • grade 4
  • tumor of cerebellum
  • children
  • metastasizes through CSF pathways
  • inc ICP signs (headache, vomiting, papilledema)
  • gait, nystagmus, dysmetria –> cerebellum affected
  • tumor responds to chemo and good outcome if has not spread through CSF
  • small blue cells
  • originates from external granular cell layer over cerebellum
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67
Q

Describe mesenchymal and meningeal tumors

A

meningiomas

  • grade 1
  • sometimes difficult to remove surgically

hemangiopericytoma

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68
Q

Describe schwannomas

A
  • neurofibromas
  • mostly benign
  • sometimes can become malignany neurofibrosarcoma
  • 8th cranial nerve affected usually –> acoustic schwannoma
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69
Q

What are the familial tumor syndromes?

A

neurofibromatosis 1

  • AD with intra and extracranial schwann cell tumors
  • see optic gliomas, astrocytomas, and meningiomas

neurofibromatosis 2
- bilateral vestibular schwannomas and multiple meningiomas

tuberous sclerosis

  • AD mutation in TSC1 and TSC2
  • hamartin and tuberin bind to inhibit kinas mTOR
  • hamartomas and benign neoplasms of brain
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70
Q

What are the most common CNS metastases?

A
  • lung, breast, melanoma, kidney, GI

- meninges

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71
Q

How is MS classified?

A
  • on phenotype not pathology

1) relapsing-remitting (85%)
2) primary progressive
3) secondary progressive
4) relapsing progressive

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72
Q

Who does MS usually affect?

A
  • young women (15-45yo)

- caucasians

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73
Q

What are type1/2 subtypes of MS associated with?

A
  • encephalomyelitis
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74
Q

What are type3/4 subtypes of MS associated with

A
  • oligodendrocyte dystrophy
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75
Q

What are the genetics involved in MS?

A
  • risk linked to DR2, IL7, IL2 receptor mutations

- inc risk in family members by 10-20x and twins

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76
Q

What environmental factors play a role in MS?

A
  • EBV
  • smoking inc 2x
  • vit D defic
  • obesity in young women
  • AI dysfcn (T cells cross BBB and damage myelin)
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77
Q

What is the DDx for MS?

A

infection, tumor, metabolic, inflam, vascular, cervical spondylosis, disc herniation, Arnold-Chiari, syringomyelia, heriditary ataxias, degen (ALS)

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78
Q

How does MS present clinically?

A
  • clinically isolated syndrome is first attack
  • radiologically isolated syndrome: see findings on MRI but no symptoms
  • early: onset is unifocal - optic neuritis, single cord lesion, numbness, tingling, gait, weakness, diplopia, urinary problems
  • later: multifocal - fatigue, sex dysfcn, depression, cog dysfcn, pain, dysphagia, hearing loss
  • neuro exam shows asymmetric, UMN signs, dec visual acuity, optic atrophy, nystagmua, sensory loss, ataxia, tremor
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79
Q

How do you diagnose MS?

A
  • multiple CNS lesions
  • RRM: 2+ attacks 30+ days apart
  • PPMS: min 12mos of progression and symptoms

path:

  • demyelination
  • perivasc lymph infiltrate
  • axonal loss, axon bulbs
  • gray matter lesions
  • lymph node with B cells in meninges

MRI:

  • T1: holes –> axonal damage; enhancing lesions –> BBB damage
  • T2: bright lesions
  • atrophy: hydrocephalus ex vacuo: enlarged ventricles due to atrophy

CSF:

  • protein normal
  • WBC normal
  • glucose always normal
  • inc IgG
  • myelin basic protein elevation is non specific

Other:
- prolonged conduction due to demyelination

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80
Q

How do you treat MS?

A

Acute attacks:

  • methyprednisolone
  • plasma exchange
  • treat symptoms

Immunomodulators:

  • IFNbeta, ABCR
  • tysabri (AB to integrin that allows lymphoctes to bind and go through BBB) –> high risk of PM

prognosis:

  • BAD if old, african american, male, high relapse, early disability
  • GOOD: if young, caucasian, female, low relapse rate, nonsmoker
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81
Q

Discuss the clinical presentation, most common organisms for different age groups, basic CSF profile (cell # and type, glucose, protein) for acute bacterial meningitis

A

Clinical presentation:

  • medical emergency
  • 2 out of 4 of: fever, headache, neck stiffness, and altered mental status
  • altered consc, seizures, N/V, myalgias, CN palsies, focal deficits, papilloedema
  • median age is 42

Age group bacteria:

1) less than 2mos:
- S. agalactiae (GBS)
- gram neg rods (enterobacteriacae)
- L. monocytogenes

2) 2-23mos
- Strep pneumoniae
- N. meningitides
- S. agalactiae (GBS)
- H. influenzae

3) 23mos-34yrs
- N. meningitides
- S. pneumoniae
- H. influenzae
- S. agalactiae
- L. monocytogenes

4) >35yrs
- S. pneumoniae
- N. meningitidis
- H. influenzae
- L. monocytogenes

CSF profile:

  • 100-10k WBC mostly PMN
  • protein high >50
  • glucose low less than 40
    • bacteria
  • get gram stain
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82
Q

Discuss the basic medical management for bacterial meningitis in different age groups

A

1-3mos:
- ampicillin AND cefotaxime

3mos-50yrs:
- ceftriaxone OR cefotaxime AND vancomycin

> 50yrs:
- ceftriaxone or cefotaxime AND vancomycin AND ampicillin

any age:

  • this is hospital acquired or recent head trauma, IC, or alcoholics
  • vancomycin AND meropenem (and maybe ampicillin)
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83
Q

Discuss how to distinguish the clinical features and most common viruses in cases of viral meningitis and viral encephalitis

A

Most common viruses:

  • enterovirus
  • HSV-2
  • arboviruse
  • HSV-1
  • EBV
  • VZV
  • HIV
  • HHV-6
84
Q

Discuss the clinical features, most common organisms, basic CSF profile, and key diagnostic tests for viral meningitis and encephalitis

A

1) viral meningitis

Clinical features:
- headache, fever, meningeal irritation (milder than bacterial meningitis)

Diagnosis:

  • CSF lymphocytic pleocytosis/normal glucose
  • PMNs may predom in 1/2 of WNV cases
  • PCR amplification
  • viral cultures
  • CSF IgM of arboviruses

Treatment:

  • acyclovir for HSV and VZV
  • antiretrovirals for HIV
  • foscarnet, ganciclovir and cidofovir for CMV
  • rimantidine for flu
  • pleconaril for enterviruses
  • supportive treatment for WNV

2) viral encephalitis

Clinical features:

  • infection of brain tissue (not just subarac space)
  • altered consciousness, fever, and headache
  • seizures, focal neuro signs/symptoms, personality change, alteration in mental status/level of consc, aphasia, hemiparesis, ataxia, CN palsies, visual loss

Etiologies:

  • 60% no cause
  • can be autoimmune

Diagnosis:

  • CSF pleocytosis
  • EEG abnormalities
  • PCR amplification of viral nucleic acid from CSF
  • WNV IgM

CSF Profile:

  • 10-2k WBC
  • lymphocytes
  • normal glucose
  • normal/elevated protein
  • do PCR

Treatment:

  • acyclovir for adult HSV
  • acyclovir for neonatal HSV
  • acyclovir for VZV
  • ganciclovir for CMV
  • none for WNV
85
Q

Describe the basic clinical and CSF profile for chronic meningitis cases and know the most common causes of chronic meningitis in the US

A

a

86
Q

Understand that the basis for the receptor (generator) potential is the opening or closing of different ion channels. What is a transduction channel and how does it differ from voltage-dependent ion channels? Why are APs necessary to transmit info in long sensory receptors?

A
  • stimulus affects sensory receptors and elicits a change in membrane potential
  • APs are not necessary in short channels because the depol or hyperpol effective changes the Vm to affect NT release since the cell is so small
  • long cells needs APs to propagate info down to the end of the cell
87
Q

Understand that in different sensory systems stimulation by the sensory stimulus results in either depol, hyperpol, or oscillatory changes in membrane potential. Thus in mechanoreceptors, pushing on the membrane results in depol, in the photoreceptor, light elicits hyperpol and in the auditory system, sound elicits oscillatory changes in membrane potential

A

Mechanoreceptors:

  • nonselective cations with reversal potential close to 0 so have depol
  • mechanosensitive cation channels open after touch and depol sensory ending

Rod photoreceptors:

  • closure of receptive area cation channels
  • short receptor cells with -40mV of membrane potential
  • high cGMP and lots of opened cGMP-gated cation channels at rest that bring in Na
  • rhodopsin is a 7 transmembrane protein
  • 1cis-retinal absorbs light and changes to 1-trans-retinal –> conformational change in receptor to metarhodopsin –> G protein called transducin is stimulated –> activates a cGMP PDE to break down cGMP –> closure of cGMP-gated cation channels –> hyperpol
  • does not fire APs

Auditory fibers:
- respond to stimulation with oscillatory change in potential

88
Q

Understand the concept of labeled lines: how do we perceive the modality of a stimulus? What is the route generally taken by sensory information that will reach sensory cortex to become conscious? Understand that, with the exception of the olfactory system, sensory systems send axonal input into the thalamus where they convey info, through synaptic input, into thalamic neurons. Thalamic neurons then convey info to sensory cortex

A

Modality:

  • sensory receptors in each sensory organ respond to specific stimuli
  • determined by selectivity of the sensory receptor cells

Labeled lines:

  • conscious appreciation of sensory modality is determined by specific neuronal connections from sensory organs through thalamus to cortex
  • conscious sensation is relayed through thalamus to cortex; other is reflex
  • different info go to different areas (visual to LGN to occipital while auditory to MGN to temporal)
  • olfactory does not have to go through thalamus to get to olfactory cortex
89
Q

Explain how stimulus intensity is encoded by sensory receptors. How is the encoding of stimulus intensity different between short and long receptors?

A
  • intensity is the magnitude of the generator potential increases as the intensity of the stimulus is increased
  • cells that respond with depol become more depol and cells that respond with hyperpol become more hyperpol
  • fraction of time the channel is open depends on stimulus intensity
  • weak touch = channel is open for a small percent of time; strong touch = channel is open most of the time
  • long sensory receptor cells code stimulus intensity as an inc in AP firing frequency
90
Q

How are peripheral nerves innervating the skeletal muscles and the skin classified in terms of conduction velocity and size? What is the relationship between size/myelination and conduction velocity? What kind of info do different size peripheral nerves carry?

A
  • classes of fibers according to conduction velocity
  • C fibers: small unmyelinated axons about 1um in diameter and .4-2m/s
  • larger size/myelination = vaster conduction velocity

Aalpha:

  • Ia - muscle spindle afferent
  • Ib - tendon organ afferent

Abeta:
- II - mechanoreceptors of skin, secondary muscle spindle afferents

Adelta:
- III - sharp pain, cool temp, extreme hot

C:
- IV - warm temp, burning pain, itch, crude touch (unmyelinated)

91
Q

Discuss the classification of sensory receptors of the skin in terms of adaptation properties and receptive field. Which of these receptors detect vibration? touch? What is meant by receptive field? How are sensory receptors of skin classified in terms of receptive field?

A
  • receptive field is the area of the skin in which a mechanical stimulus elicits a response from the cell

Meissner’s corpuscles:

  • in fingertips
  • RA is few mm
  • rapidly-adapting afferents

Pacinian corpuscles:

  • RA covers palm of hand and deeper in skin
  • rapidly adapting
  • vibratory stimuli

Merkel’s disk:

  • small fields
  • slowly adapting

Hair follicle receptor:
- rapidly adapting

Ruffini free nerve endings:

  • large RA
  • slowly adapting
  • stretch
92
Q

Describe the flow of info (anatomical pathway) along the medial lemniscal and trigeminal lemniscal system

A
  • mechanoreceptors in skin have large myelinated axons (Abeta) –> cell bodies of mechanoreceptors in dorsal root ganglia –> enter spinal cord and split –> reflex pathway and ascending pathway to DCML through FC and FG to NC and NG in medulla –> synapse is made then cross midline to form medial lemniscus –> joined in midbrain by fibers from trigeminal nuclei –> ascend and synapse in ventro basal part of thalamus (VPL-trunk and limbs and VPM-head nucleus) –> areas 3, 1, and 2 of posterior bank of central sulcus (S1) –> M1 and S2
  • LE go up FG while UE go up FC

Trigeminal lemniscal pathway:

  • afferent info regarding touch, proprioception, pain, and temp on face and head go through this nerve and also motor and autonomic neurons
  • opthalmic, maxillary, and mandibular branches
  • trigeminal ganglion –> principal nucleus of trigem complex in pons –> synapses onto secondary neuron that crosses over and ascends –> joins medial lemniscus –> goes to VPM of thalamus –> primary somatosensory cortex
93
Q

Define somatotopy and describe why some regions (e.g. mouth and hands) are enlarged compare to others in the somatotopic map in primary somatosensory cortex

A
  • somatotopy is the precise and orderly mapping of the body surface onto the cortex
  • neighboring cells throughout all levels of the somatosensory system can make a coherent contiguous map of the body surface
  • hands and feet are richly innervated by primary afferents so they have larger areas of cortex devoted to them
94
Q

Describe parallel somatotopic maps in different Brodmann’s areas in somatosensory cortex

A
  • individual maps for each sensory modality
  • 1 and 2 arranged to somatosensory but respond to more complex stimuli
  • 3a and 3b respond to simple punctate stim, but 1 and 2 that are sensitive to direction and orientation and shape-sensitive due to convergent input from 3a and 3b to 1 and 2
  • thalamus projects widely to more than just primary somatosensory cortex –> multiple maps arise due to parallel processing of different sensory modalities by cortex
  • S2 are more complex stimulus than S1
  • S2 info comes from S1
95
Q

Describe cortical barrels or columns

A
  • circular arrangements of cells that run throughout the cortical depth
  • it is a morphological specialization of the cortex that reflects a functional organization
  • cells in a column have similar modality and nearly identical receptive field location
  • different 6 layers project to and receive input from different areas of the brain (4 from thalamus, 6 to thalamus, 5 to other subcortical structures, 2 and 3 to other somatosensory cortex areas)
96
Q

Recognize the pathways for processing of pain and temp info and describe where pain and temp info is first detected, where the info first enters the CNS and how the info gets to the brain

A

anterolateral system:
- warm and cool receptors at skin –> DRG send axons into CNS and synapse with dorsal horn of spinal cord/spinal trigeminal nucleus –> cross anterior white commissure –> ascend contralaterally –>

1) at medulla:
- body temp info goes to reticular formation then hypothalamus
- spinoreticular
- pain inputs –> forebrain arousal and elicit emotional responses

2) at midbrain:
- go to mesencephalon at periaqueductal gray region (PAG)
- spinomesencephalic
- descending control of pain

3) at thalamus:
- go to ventrobasal nuclei of thalamus (VPL) then somatosensory cortex
- spinothalamic tract
- pain info

Trigeminal system:
- pain and temp inputs from head and neck –> trigemnial ganglion neurons –> enter CNS at pons and descend to caudal position –> synapse at spinal trigeminal nucleus in rostral spinal cord to caudal brain stem

97
Q

Recognize the type of receptors that detect temp info

A

1) cool receptors
- 10-37deg
- Adelta fibers

2) warm receptors
- 30-48deg
- C fibers

  • extreme hot (>43) Adelta
  • extreme cold (less than 5) C
98
Q

Describe how temp receptors code their info

A
  • temp info from periphery is transduced into a receptor potential –> triggers APs
  • frequency of APs gives info about intensity of stimulus
  • info about actual temp and change in temp
99
Q

Discuss the types of manipulations that distinguish first pain from second pain

A
  • first pain is transmitted by Adelta fiber and is tolerable, localized, pricking (smaller RF)
  • second pain is transmitted by C fiber and is burning, intolerable, and diffuse (larger RF)
100
Q

Discuss the stimuli that activate polymodal receptors

A
  • C fiber afferents

- activated by high intensity mechanical, chemical, or thermal stimuli

101
Q

ID chemicals that acts pain activators and sensitizers

A

Activators:

  • direct act of nociceptors
  • bradykinin from kininogen; tissue damage –> proteases degrade serum proteins –> bradykinin –> activates pain receptors of Adelta and C
  • potassium
  • 5HT
  • acids

Sensitizers:

  • threshold for act of nociceptors decreases –> makes more sensitive (hyperalgesia)
  • prostaglandins
  • substance P; released by C fibers after repetitive elec stim
  • ATP
  • ACh
  • 5HT
102
Q

ID the stimuli that activate the VR-1 receptor. Where is the VR-1 receptor located?

A
  • vanilloid receptor (activated by vanilloid moiety containing compounds)
  • VR-1 is the capsaicin receptor and is strongly activated by capsaicin and weakly activated by acids and moderate heat
  • VR-1 is on polymodal receptors
  • when receptor is act –> NSC channel opens –> depol
103
Q

Discuss the type of pain info that is carried by C fiber afferents

A
  • extremely cold temperatures

- second pain (burning, intolerable, diffuse)

104
Q

ID the location of the first synapse in the pain pathway and the NTs that operate at this synapse

A
  • afferent fibers synapse in the dorsal horn of the spinal cord or the trigeminal spinal nucleus
  • glutamate is the primary exc NT
  • C fibers terminate in Rexed’s laminae in the dorsal horn of spinal cord
  • Adelta fibers terminae in other laminae
  • substance P can also be released during intense stimulation –> binds to neurokinin1 receptor –> closes K channels –> depol
105
Q

Describe the differences between and the properties of AMPA and NMDA receptors at the dorsal horn synapse

A
  • major NT released by pain neurons in dorsal horn is glutamate
  • AMPA and NMDA are both ionotropic and activated by glutamate
  • AMPA –> rapid
  • NMDA –> slow and require a simultaneous postsyn depol and glutamate to open
  • C fibers stimulate AMPA receptors first; if strong stimulation then postsyn depol during later periods of stimulation –> NMDA also activated
  • ## NMDA makes long lasting changes in exc: NMDA receptor is phosphorylated by PKC and TKs –> doesn’t need depol to activate it anymore
106
Q

Describe the bases for the analgesic action of aspirin

A
  • aspirin prevents COX converting AA to PG –> dec sensitization
107
Q

Describe the basis for the triple response

A
  • reddening, wheal, and flare after injury
  • tissue damage –> bradykinin production –> vasodilation –> heat/red and awelling
  • flare is due to large receptive fields of C fibers activated by bradykinin –> depol and APs –> go to cell body and more peripherally –> substance P released along collateral terminals –> milder pink vasodilation aka flare due to axon reflex
108
Q

ID the location of action and the effects of Substance P

A
  • sensitizer that dec threshold activation of nociceptors
  • from C fibers
  • released at synapse and in periphery from axon during periods of reptitive stimulation
109
Q

Describe the role of the PAG in modulation of pain

A
  • stimulation of PAG causes a powerful analgesia
  • PAG neurons in midbrain project to nucleus raphe magnus in medulla which are serotonergic –> project to spinal cord via dorsal lateral funiculus –> 5HT leads to inhibition of 2nd order neurons of dorsal horn by exciting inhibitory interneuron that uses enkephalin as NT by blocking presyn VGCC and opening postsyn K channels
110
Q

Describe the role of the PAG in modulation of pain

A
  • stimulation of PAG causes a powerful analgesia
  • PAG neurons in midbrain project to nucleus raphe magnus in medulla which are serotonergic –> project to spinal cord via dorsal lateral funiculus –> 5HT leads to inhibition of 2nd order neurons of dorsal horn by exciting inhibitory interneuron that uses enkephalin as NT by blocking presyn VGCC and opening postsyn K channels
  • opiates also strengthen the effect of the PAG
111
Q

Describe the bases for the placebo effect and stress-induced analgesia

A

Stress:
- stress leads to inc activity of limbic system –> act of PAG –> inh of second order neurons of dorsal horn in pain pathway

Placebo:

  • naloxone blocks placebo effect –> endogenous opiate release associated with placebo effect
  • PAG receives input from limbic system and cortex
  • expects pain relieving drug –> activity in cortex/LS –> PAG activation through inc secretion of endorphins –> inhibition of second order neurons
112
Q

Describe mechanisms underlying neuropathic pain

A

Peripheral mechanisms:

  • spontaneous activity in primary sensory neurons –> stimulus independent pain conditions
  • sensory afferent have 2 types of Na channels: one sensitive to TTX and one resistant to TTX, which plays a big role in setting inflam pain thresholds (w/o = higher pain threshold)
  • ATP after cell death binds to purinergic receptors on sensory neurons and affects TTXres Na channel
  • after damage, Na channels are weird –> spont discharge of primary pain afferents so Na channel blockers can help, but can cause CNS and CV problems

Central mechanisms:

  • after injury –> neuronal loss, dec in GABA and GABA receptors –> dec in inhibition of dorsal horn neurons –> inc exc
  • drugs that augment central inhibition can help
  • injury to C fibers –> nerve sprouting and weird signaling
  • usually, SG receives inputs from pain C fibers, but after injury have Abeta afferents which control non pain afferents
  • injury leads to inflam at lesion, DRG, and spinal cord –> astrocytes and microglia and immune cells maintain neuropathic pain
  • macrophages secrete TNF that sends signal to change TTXres Na channels
  • in dorsal horn, ATP activates microglial cells to secrete BDNF –> changes Cl reversal potential so that GABA causes exc not inh
  • dec inh in dorsal horn = hyepralgesia
113
Q

Why does rubbing a hurt area help?

A
  • touch activates non-nociceptive Abeta fibers –> activation of dorsal horn interneurons –> inhibit synapses on nucleus that is activated by nociceptive fibers
  • gate control theory
114
Q

Describe the general structure of local anesthetics, and key chemical properties of the structures

A
  • 3 parts: 1) lipophilic aromatic, 2) intermediate alkyl chain, 3) hydrophilic amine portion
  • intermediate chaine is either an ester or amide
115
Q

Describe the structural and chemical differences between amide and ester local anesthetics

A
  • one i = ester
  • two i = amides
    ester = shorter and no nitrogen
  • amide is longer and with nitrogen
116
Q

Describe the role of pH in determining the effectiveness of local anesthetics

A
  • weak bases with pKa from 7.7-9
  • partly ionized at 7.4
  • neutral/ion = 10^(pH-pKa)
  • needs both charged and neutral form so pH maintenance is important
117
Q

Describe the molecular target and structure-based mechanism of action of local anesthetics

A
  • block of Na channels depends on state of channels
  • binding site is in a wide region of the water filled pore of Na channel
  • drug is too big to get to binding site via extracellular entrance so goes via intracellular pore entrance
  • drug in neutral crosses plasma membrane to become intracellular and then are able to bind to site when Na channel opens and in charged form
  • can also go through protein wall of the channel when closed or open
  • use-dep block: more the channel is open, greater the degree of local anesthesia
  • block flow and stabilize inact form
118
Q

Describe the physicochemical properties of local anesthetics that determine potency, onset, and site of drug action

A

Physicochemical properties:
- potency correlated to lipid solubility

Onset:

  • speed is determined by pKa
  • lower pKa inc lipid solubility by inc fraction of uncharged molecules
  • lower pKa and higher lipid solubility = more rapid onset

Duration of action:

  • related to protein binding capacity
  • inc percentage of bound to plasma protein = longer duration

Termination:

  • esters are hyrdolyzed by sterase
  • amides are metabolized by liver
119
Q

Describe the methods of local anesthetic application

A

1) topical:
- directly onto skin, cornea, mucous membranes
- abs into circulation, which can be toxic

2) infiltration:
- injection into tissue
- usually underlying organs are unaffected but need large doses that might be abs into circulation

3) nerve block:
- injection of high concentration near a peripheral nerve or nerve plexus
- larger regions can be anesthetized

4) IV regional (Bier’s Block):
- use a tourniquet and inject anesthetic with a catheter
- have tourniquet pain and ischemic injury

5) spinal:
- inject into CSF
- large regions
- good really only for lower abdomen and LE surgeries

6) epidural:
- inject just outside dura of spine
- can use catheter for repeated/cont dose
- plasma levels are higher –> toxic

120
Q

Describe the rationale for use of a vasoconstrictor with a local anesthetic

A
  • prolongs duration of conduction blockage
  • delays systemic absorption of anesthetic by reducing blood flow
  • ## epinephrine is typical vasoconstrictor
121
Q

Describe the side effects of local anesthetics

A
  • can block AP conduction in all organs that generate APs using VGSCs –> convulsions and interference with ANS function
  • CV problems
  • can cause arteriolar dilation
  • local anesthetics can enter fetal circulation
  • can inhibit neuromuscular transmission by blocking ACh receptors
  • can be allergic to local anesthetics (use promethazine)
122
Q

Describe how local anesthetics differ in action from tetrodotoxin and saxitoxin

A

a

123
Q

Describe how local anesthetics differ in action from tetrodotoxin and saxitoxin

A
  • TTX and STX act by binding to and blocking extracellular entrance of Na channels
  • Na channels in nerve and muscle have nanomolar affinity; cardiac Na channels have micromolar affinity –> paralyzes resp muscles not heart
124
Q

Describe how local anesthetics differ in action from tetrodotoxin and saxitoxin

A
  • TTX and STX act by binding to and blocking extracellular entrance of Na channels
  • Na channels in nerve and muscle have nanomolar affinity; cardiac Na channels have micromolar affinity –> paralyzes resp muscles not heart
125
Q

Recognize the epidemiological implications of HA

A
  • > 50% of reasons people see a doctor

- 15% of US will seek advice about HA

126
Q

Differentiate the difference between a primary and secondary HA syndrome

A
  • primary has no known cause (migraine) and are episodic/chronic
  • tension types, migraines, trigeminal autonomic cephalalgias
  • secondary is attributed to a systemic or cephalic disorder (meningitis) and usually constant
127
Q

Recognize the common primary HA syndromes: migraine, tension type, cluster, and trigeminal neuralgia

A

Migraine:

  • > 5 recurring HAs that last 4-72hrs and are 2 of the following: unilateral, pulsating, moderate/severe, and inc with physical activity and must also have either nausea/vomiting or photophobia/phonophobia
  • 4 stages: 1) premonitory (alterations in mood), 2) aura (neuro symptoms) 3) HA, 4) postdrome (exhaustion and lethargy)
  • triggers are missed meals, little sleep, alcohol, etc.
  • treatment is abortive and sometime preventative –> NSAIDs (nonspecific) or serotonin receptor agonists (specific) that are selective (triptans) or nonselective (egotamine deriv)
  • prophylactics are beta blockers, CCBs, TCADs, anti epilectics
  • migraine aura: 2 epsiodes with visual, sensory, language, motor, BS, retinal changes AND 2 of unilateral, gradual development over 5min, lasting 5-60min, or with a HA; visual auras are most common

Tension type:

  • > 10 episodes of HA lasting 30min-7days with 2 of: pressing/tight sensation, mild to moderate severity, bilateral, not aggravated by physical activity
  • NO nausea or vomiting and only one or none of photophobia or phonophobia
  • featureless headache and opposite of migraine
  • abort HA with NSAIDs; prevent with TCADs, SSRIs, psycho and physical therapy

Cluster:

  • > 5 episodes of severe, unilateral, periorbital/temporal pain lating 15-180min
  • recurs ever other day up to 8x a day
  • ipsilaterally can see: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, eyelid edema, ptosis, miosis, facial swelling, ear fullness, agitation
  • more common in men
  • triggers are alcohol or vasodilators
  • abort with O2, triptans, ergotamine deriv, lidocaine, corticosteroids
  • prevent with CCBs

Trigeminal Neuralgia:

  • brief pain in trigeminal nerve distribution from less than 1sec to 2 min
  • intense, sharp, superficial, or stabbing
  • triggered by sensory stimulation like chewing or brushing teeth
  • can be primary or secondary
  • treat with anti-epileptics or baclofen
128
Q

Describe the potentially dangerous conditions often presenting with a HA: meningitis, trauma to the head, subarac hem, giant cell arteritis, idiopathic intracranial HTN

A

Head injury:

  • pain w/in 7 days of injury and resolved w/in 3mos
  • dizziness, poor concentration, irritability, insomnia

Infection/meningitis:

  • acute pain
  • HA, fever, neck stiffness
  • N/V, altered consciousness
  • kerning/brudzinski signs
  • diagnose with LP
  • treat with antibiotics

Subarach hem:

  • sudden, intense HA
  • diffuse pain
  • trauma, ruptured aneurysm, AVM
  • neck stiffness, photophobia, N/V, neuro signs on exam
  • dec arousal
  • get CT
  • get LP

Giant cell arteritis:

  • jaw claudication, temporal artery tenderness, joint pain, fever, malaise, weight loss
  • ESR and CRP elevated
  • treat with steroids

Inc ICP:

  • HA worse with exertion, retro orbital pain, N/V, vision loss
  • 6th nerve palsies, papilledema
129
Q

Describe the potentially dangerous conditions often presenting with a HA: meningitis, trauma to the head, subarac hem, giant cell arteritis, idiopathic intracranial HTN

A

Head injury:

  • pain w/in 7 days of injury and resolved w/in 3mos
  • dizziness, poor concentration, irritability, insomnia

Infection/meningitis:

  • acute pain
  • HA, fever, neck stiffness
  • N/V, altered consciousness
  • kerning/brudzinski signs
  • diagnose with LP
  • treat with antibiotics

Subarach hem:

  • sudden, intense HA
  • diffuse pain
  • trauma, ruptured aneurysm, AVM
  • neck stiffness, photophobia, N/V, neuro signs on exam
  • dec arousal
  • get CT
  • get LP

Giant cell arteritis:

  • jaw claudication, temporal artery tenderness, joint pain, fever, malaise, weight loss
  • ESR and CRP elevated
  • treat with steroids

Inc ICP:

  • HA worse with exertion, retro orbital pain, N/V, vision loss
  • 6th nerve palsies, papilledema
130
Q

What are drugs for preventing tension HAs?

A

TCADs

SSRIs

131
Q

What are drugs for aborting tension HAs?

A

NSAIDs

acetaminophen

132
Q

What are drugs for preventing migraines?

A 
beta blockers
anticonvulsants
antidepressants
CCBs
NSAIDs
5HT2 receptor antag
133
Q

What are drugs for aborting migraines?

A 
DHE
ergotamine
isometheptene
NSAIDs
tramadol
triptans
134
Q

What are drugs that prevent cluster HAs?

A

lithium
methersgide
verapamil

135
Q

What are drugs that abort cluster HAs?

A 
DHE
ergotamine
glucocorticoids
lidocaine
O2
sumatriptan
136
Q

What is the currently understood mechanism for migraines?

A
  • primary neuronal dysfunction leads to a sequence of intracranial and extracranial changes that account for migraine symptoms
  • 5HT plays a role
  • first phase is cerebral vasoconstriction and ischemia with 5HT release
  • second phase is cerebral vasodilation and pain with trigeminal neurovascular system releasing vasoactive peptides, substance P, and other triggers for vasodilation and neuroinflammation of pial and dural vessels

generally:
- trigeminal neurovascualr dysfcn –> trigeminal neurovascualr activation –> release of vasoactive peptides –> neuroinflammation (PG release) and vasodilation of pial and dural vessels –> moderate to severe pain

  • NSAIDs target neuroinflammatory PG release
  • triptans and ergot alkaloids target TG NV act, release of vasoactive peptides, and vasodilation of vessels
137
Q

What is the currently understood mechanism for migraines?

A
  • primary neuronal dysfunction leads to a sequence of intracranial and extracranial changes that account for migraine symptoms
  • 5HT plays a role
  • first phase is cerebral vasoconstriction and ischemia with 5HT release
  • second phase is cerebral vasodilation and pain with trigeminal neurovascular system releasing vasoactive peptides, substance P, and other triggers for vasodilation and neuroinflammation of pial and dural vessels

generally:
- trigeminal neurovascualr dysfcn –> trigeminal neurovascualr activation –> release of vasoactive peptides –> neuroinflammation (PG release) and vasodilation of pial and dural vessels –> moderate to severe pain

  • NSAIDs target neuroinflammatory PG release
  • triptans and ergot alkaloids target TG NV act, release of vasoactive peptides, and vasodilation of vessels
138
Q

What is the general approach to treatment of migraines?

A
  • if vomiting, pretreat with antiemetic and consider parenteral routes
  • if severe symptoms, go straight to triptans or ergot; if still no improvement go to opiates
  • if mild symptoms, start with NSAIDs then add acetaminophen then triptans and ergots
139
Q

What is the mechanism of triptans in migraine?

A
  • first line for moderate to severe migraines
  • agonist activity at 5Ht-1B/1D receptors –> vasoconstriction of cerebral vessels, inhibition of release of vasodilatory and inflammatory peptides, prevention of activation of pain fibers in trigeminal nerve
140
Q

What are the pharmacokinetics of triptans?

A
  • oral

- poor CNS penetration

141
Q

What are the adverse effects of triptans?

A
  • tingling, flushing, dizziness, drowsiness, fatigue

- can cause coronary vasospasm and angina, MI, and arrhythmia

142
Q

What are the DDIs of triptans?

A
  • do not use with ergot alkaloid or MAOI because vasoconstriction can be additive
  • do not use with SSRIs because it inc risk for serotonin syndrome
143
Q

What is the mechanism of ergot alkaloids?

A
  • not first line
  • agonist at 5HT-1B/1D receptors
  • similar to triptans but less effective and more toxic
144
Q

What are the pharmacokinetics of ergot alkaloids?

A
  • ergotamine: oral, sublingual, rectal; slow onset; long duration
  • dihydroergotamine: intranasal and parenteral; quick onset
145
Q

What are the adverse effects of ergot alkaloids?

A
  • N/V/D

- vascular occlusion and gangrene

146
Q

What are DDIs with ergot alkaloids?

A
  • avoid nonselective beta blockers –> ischemia
  • dont use with triptan
  • dont use with CYP3A4 inhibitor –> vasospasm
147
Q

What helps prevent migraines?

A

anti-HTN agens:

1) beta blockers
- first-line
- continuous prevention
- reduce frequency and severity
- cause fatigue, exercise intolerance, depression, orthostatic hypotension

2) CCBs
- verapamil
- third line

3) ACEIs
- 2nd or 3rd line

Antidepressants:

  • amitripyline
  • second line
  • sedation

Anticonvulsants:

  • valproate and topiramate (first line)
  • nausea, tremor, weight gain, hair loss; paresthesias, lang impairment, weight loss

Botox:

  • second line
  • HA, neck pain, muscle weakness, drooping eyelids

Methysergide:

  • 5HT receptor antagonist
  • blocks vasoconstriction
  • N/V/D

NSAIDs:
- short term prevention

Dietary supplements:

  • riboflavin
  • butterbur
  • feverfew
148
Q

What are extramedullary lesions more likely to cause?

A
  • outside cord
  • early pain and UMN signs
  • pain and temp sensation evolves in an ascending fashion
149
Q

What are intramedullary tumors more likely to cause?

A
  • inside cord
  • early bladder dysfunction
  • late development of pain
  • pain and temp in a descending fashion
150
Q

Describe the somatotopic organization to the fibers in the major tracts in the spinal cord

A
  • in DCML: sacral is medial, cervical is lateral
  • in corticospinal: cervical is medial, sacral is lateral
  • in anterolateral: cervical is medial, sacral is lateral
151
Q

Where is the C5 dermatome?

A

back of shoulder and lateral arm

152
Q

Where is the C6 dermatome?

A

thumb and second digit

153
Q

Where is the C7 dermatome?

A

third digit

154
Q

Where is the T4 dermatome?

A

nipple line

155
Q

Where is the T5 dermatome?

A

xyphoid process

156
Q

Where is the T10 dermatome?

A

umbilicus

157
Q

Where is the L4 dermatome?

A

kneecap, medial leg

158
Q

Where is the L5 dermatome?

A

dorsum of foot, great toe

159
Q

Where is the S1 dermatome?

A

lateral foot, small toe, sole of foot

160
Q

Paresthesia

A

abnormal sensation (burning, pricking, tickling, tingling)

161
Q

Dyesthesia

A

impairment of sensation short of anesthesia

162
Q

Paresis

A

muscle weakness

163
Q

Dermatome

A

cutaneous area served by an individual sensory root

164
Q

Myotome

A

Muscles innervated by an individual motor root

165
Q

Radiculopathy

A

Sesnory and/or motor dysfunction due to injury to a nerve root

166
Q

Myelopathy

A

Disorder resulting in spinal cord dysfunction

167
Q

Describe functions of the 3 major spinal tracts and ID where they cross

A

Corticospinal:

  • motor control
  • crosses at pyramids of medulla

DCML:

  • touch, vibration, joint position, proprioception
  • crosses at nuclei in medulla

anterolateral:

  • pain and temperature
  • cross at the spinal level across the anterior white commissure
168
Q

ID where the nerve roots exit

A

for C1-C7: nerve roots exit above same numbered vertebra

C8 exits below C7 and above T1 vertebra

T1-2-5 exit below same numbered vertebra

169
Q

ID the spinal cord level that each vertebral body overlies

A

Upper cervical: vertebra # = cord segment #

Lower cervical: vertebra # = cord segment # + 1

Upper thoracic: vertebra # = cord segment # + 2

Lower thoracic/lumbar: vertebra # = cord segment # + 2-3

Lower edge of L1 vertebral body overlies conus medullaris

170
Q

Recognize the symptoms of a radiculopathy and understand Lhermitte’s symptom

A
  • shooting, burning, tingling pain
  • LMN signs
  • use dermatomes to localize
  • lhermitte’s sign: neck flexion results in electric shock sensation down back and into arms
171
Q

Recognize the neurologic signs used to distinguish lesions affecting the LMNs vs UMNs

A
  • LMNs muscle weakness, hypotonia, hyporeflexia, flaccid paresis, fasciculations, atrophy
  • UMNs immediate weakness and hypotonia (spinal shock) then spasticity and hyperreflexia
172
Q

Describe the major tract deficits associated with 10 spinal cord syndromes

A

1) complete cord transection:
- deficit in sensory and motor levels below lesion
- spinal shock followed by UMN signs

2) central lesions:
- syringomyelia, ependymoma
- pain/temp loss at lesion
- sparing of position sensation
- cape dist if cervical

3) posterior column syndrome:
- DCML affected
- bilateral loss of position and vibration sense

4) combined anterior horn cell-pyramidal tract syndrome:
- CS and LMN cells
- loss of bilateral strength

5) Brown-sequard (hemi-section)
- crossed ALS, uncrossed DCML, crossed CS
- loss of pain and temp contralat below lesion and loss of position and strength ipsilat below lesion

6) Posterolateral column syndrome:
- DCML + CS
- bilateral loss of position and vibration and strength

7) anterior horn cell syndrome:
- LMNs
- bilateral loss of strength

8) anterior spinal artery occlusion:
- ALS + CS
- bilateral loss of strength and pain and temp
- sparing position

9) pyramidal tract syndrome:
- CS
- bilateral UMN weakness and spastic gait
- sparing of all sensory tracts and bladder function

10) myelopathy with radiculopathy
- any or all 3 tracts
- bilateral UMN with spastic gait
- possible bladder dysfunction

173
Q

Distinguish conus medullaris syndrome from cauda equina syndrome

A

CM: S2-S5, late pain in thighs and butt, pelvic floor muscle weakness, symmetric numbness, early bladder dysfcn, early sex dysfcn

CE: L1-S5, early root pain to legs, leg weakness, asymmetric numbness, late bladder dysfcn, late sex dysfcn

174
Q

Recognize the basic neural pathways involved in the control of micturition

A

1) detrusor muscle:
- activated by pregang para from S2-S4

2) involuntary sphincter:
- pregang symp outflow from T10-L2

3) pelvic floor skeletal muscle:
- alpha motor neurons from S2-S4

175
Q

Recognize that injuries at different levels can result in a flaccid or spastic bladder

A
  • if para LMNs are injured –> bladder cannot contract and no sensation of a full bladder –> outflow incontinence and won’t hold urine
  • desc pathways are injured –> UMN signs –> flaccidity then spasticity –> frequency and urgency
176
Q

Recognize the sensory territory, unique motor territory, and reflex components of C5, C6, C7 and L4, L5, S1 nerve roots

A

C5

  • motor: deltoid, infraspinatus, biceps
  • sensory: shoulder, upper lateral arm
  • reflex: biceps

C6:

  • motor: wrist extensors, biceps
  • sensory: 1st and 2nd digits
  • reflex: biceps, brachioradialis

C7:

  • motor: triceps
  • sensory: 3rd digit
  • reflex: triceps

L4:

  • motor: psoas, quads
  • sensory: knee, medial leg
  • reflex: patellar

L5:

  • motor: foot dorsiflexion, big toe extension, foot eversion and inversion
  • sensory: dorsum of foot, big toe
  • no reflex

S1:

  • motor: foot plantar flexion
  • sensory: lateral foot, small toe, sole of foot
  • reflex: achilles
177
Q

Describe ALL of the material presented under reflexes except special situations

A
  • biceps: C5, C6
  • brachioradialis: C6
  • triceps: C7
  • patellar: L4
  • achilles: S1
  • plantar response: scrape from heel to toe –> arch toes; if extend toes that is Babinksi’s sign
  • hold patients middle finger and flick fingernail downward –> thumb flexion and adduction is hoffman’s sign
178
Q

What are the phases of Traumatic Spinal Cord Injury?

A

Phase 1:

  • complete loss/weakening of all reflexes below injury
  • lasts for a day

Phase 2:

  • return of some but not all reflexes below injury
  • bulbocavernous reflex reappears because it is polysynaptic
  • deep tendon reflexes take longer

Phase 3:

  • hyperreflexia
  • interneurons and LMNs below injury sprout

Phase 4:

  • chronic spasticity
  • 1month+
179
Q

Recognize the medical circumstances in which opioids are indicated and contraindicated

A

indicated:

  • pain from malignancy
  • surgery
  • post op pain
  • obstetric anesthesia
  • patient controlled analgesia
  • cough
  • anti diarrheal

contraindicated:

  • resp dysfunction
  • head injury
  • hypotension
  • shock
  • hypothyroidism
  • impaired hepatic function
180
Q

Discuss the potential adverse interactions of opioids with other drugs

A
  • barbiturates: CNS depression
  • phenothiazines: inc analgesia but inc resp dep, inc hypotension
  • MAOI and TCADs: inc resp dep, seizures
181
Q

Discuss the life-threatening side effects of opioid drugs and the appropriate means to avoid/treat these action

A
  • respiratory depression due to dec in CO2 sensitivity in brainsteam (inc CO2 in blood –> cerebral vasodilation)
  • nausea and vomiting
  • cough suppression
  • miosis
182
Q

Describe the mechanism by which opioids act upon the CNS and PNS

A

1) decrease neuronal excitability through hyperpolarization
2) direct inhibition of Ca channels, act of K channels, inh of NT release
3) inh of cAMP synth

inhibition of transmission in pain pathway:

  • inh NT release from primary afferent terminals in dorsal horn
  • inh of anterolateral ascending output neurons
  • act of desc inh systems in medulla, PAG, mediated by 5HT and NE
183
Q

Define tolerance and dependence and discuss the degree to which these phenomena develop in various opioid sensitive systems

A
  • tolerance: a dec response to a drug due to previous exposure
  • factors that affect tolerance: frequency, dose, duration of use
  • does not affect GI and pupil constriction
  • dependence: the continued use of a drug to maintain a normal state or craving for a drug
  • physical dependence is usually mild with short term opioids
  • withdrawal: flu-like symptoms (dilated pupils, insomnia, restless, yawning, rhinorrhea, sweating, diarrhea, nausea, chills)
  • clonidine is used to treat withdrawal
184
Q

Identify the sites of opioid action in the CNS and periphery

A
  • analgesia: periaqueductal gray (desc pain), medulla nuclei (resp dep), spinal cord dorsal horn (asc pain)
  • limbic and motor CNS: amygdala, hippocampus, straitum
  • reinforcement regions in CNS: ventral tegmentum, nucleus accumbens
  • gut: myenteric plexus
185
Q

Recognize that in chronic pain associate with terminal malignancy, the responsibility of the physician is to ensure that the patient is pain-free and comfortable

A

aite

186
Q

Recognize the different classes of endogenous opioids and list representative of each class

A
  • enkephalins: NTs and hormone, broken down by peptidases so act on short distances, brain and SC
  • endorphins: NT and hormone, hypothalamus and pituitary (beta endorphin)
  • dynorphin: dynorphin A is most biologically active and kappa selective
  • endomorphins: mu receptor selective
187
Q

Recognize the names and describe the uses of opioids agonists from each classification

A 
Opioid phenanthrene (mu agonists)
- morphine, heroin, codein, oxycodone, tramadol

Meperidine and other phenylpiperidine (mu agonists)
- meperidine, loperimide, fentanyl,

Methadone phenyl heptamines (mu agonists)

  • methadone
  • propoxyphene

Mixed agonist/antagonists and partial agonists (benzmorphans)

  • buprenorphine
  • pentazocine
  • butorphanol
  • nalbuphine
188
Q

mu receptors (u)

A
  • central analgesia
  • resp depression
  • beta endorphin
  • morphine
189
Q

delta receptors

A
  • analgesia
  • met/leu enkephalin
  • beta endorphin
  • no drugs
190
Q

kappa receptors

A
  • spinal analgesia
  • dynorphin 1-17
  • pentazocine
191
Q

What are the behavioral effects of opioid drugs?

A
  • euphoria (mu receptors)
  • dysphoria with kappa receptors (hallucinations)
  • sedation, lethargy, confusion
  • behavioral excitation (acute toxicity)
192
Q

What are the effects of opioids on the brainstem?

A
  • resp depression
  • nausea and vomiting
  • coug hsuppression
  • pupil constriction
193
Q

What are the effects of opioids on smooth muscle?

A
  • constipation
  • inc smooth muscle tone –> spasm
  • inc biliary pressure
  • urine retention
194
Q

What are the CV effects of opioids?

A
  • dec cardiac workload
  • inh of barorefelx –> ortho hypotension
  • be careful of hypovolemia
  • good for MI
  • good for pulm edema
195
Q

What are the opioid antagonists?

A
  • naloxone
  • naltrexone
  • alvimopam
  • naloxogol
196
Q

How do you classify pain?

A
  • severity, duration, and origin

Severity:
- look at behavioral, cognitive, social, and cultural aspects

Duration:

  • acute: usually due to healing of tissue damage
  • chronic: chronic disease, cancer, neuropathic

Origin:

  • nociceptive: somatic or visceral
  • neuropathic: nerve damage, abnormal operation of the nervous system
197
Q

Describe the role of each of the following pharmacotherapeutic categories in the management of acute pain (review the pharmacology that has been presented in other lectures – efficacy / pharmacokinetics / side effects): Opioid analgesics; NSAIDs - Acetaminophen - COX-2 inhibitors; Local anesthetics; and a-2 adrenergic agonists / NMDA receptor antagonists.

A

NSAIDs:
- inhibit COX-2 and PG synthesis –> reduce peripheral and central sensitization

Local anesthetics:

  • block VSSC –> reduce nociceptive stimuli AP
  • NMDA receptor antagonists –> block glutamate receptor depol at 2nd order neuron –> dec transmission of nociceptive stimuli

Modulation of transmission:

  • mu opioid receptor agonists: block glutamate-substance P release from primary neuron and hyperpol 2nd order neuron –> dec afferent evoked exc of 2nd order neuron
  • alpha2 adrenergic receptor agonists –> block glu-subsance P release etc.
198
Q

Acute pain management

A

Mild:
- treat with NSAID or acetaminophen and maybe adjuvant analgesic

Moderate:
- immediate release, short acting opioids with slow titration + non opioid and maybe adjuvant analgesic

Severe:
- immediate release short acting opioids with rapid titration + non opioid and maybe adjuvant analgesic

199
Q

Describe the pharm aspects of opioids

A
  • agonists at mu receptors
  • IV is fastest but other routes of admin
  • different duration of releases
  • side effects: constipation, N/V, sedation, resp depression, pruritus
200
Q

Describe the pharm aspects of local anesthetics

A
  • antagonists at VSSC
  • dec systemic opioid need and dec risk of opioid related side effects
  • epidural or spinal infusion or peripheral nerve block
  • side effects: neurotoxicity, hypotension, dizziness, drowsiness
201
Q

Describe the pharm aspects of NSAIDs

A
  • COX2 inhibitors –> inh PG synthesis in inflammatory cascade
  • dec post op opioid req
  • IV and oral
  • side effects: GI ulcers, inc bleedign risk, renal dysfcn, CV problems
202
Q

Describe the pharm aspects of acetaminophen

A
  • inhibits COX2 for CENTRAL sensitization only
  • alternative to NSAIDs
  • oral
  • side effets: hepatotoxicity
203
Q

Describe the pharm aspects of alpha2 adrenergic agonists

A
  • clonidine
  • act at alpha2 adrenergic receptors on dorsal horn neurons to modulate pain
  • epidural infusion
  • side effects: hypotension, bradycardia, sedation, rebound HTN
204
Q

Describe the pharm aspects of NMDA receptors antagonists

A
  • ketamine
  • block glutamate binding at NMDA receptors
  • reduce tolerance to opioids
  • IV and intranasal
  • side effects: HTN, diplopia, dizziness, arrhythmias, N/V
205
Q

Describe the approach to treating chronic pain

A
  • enhance desc inhibitory pathway: act opioid receptors (opioids) and block NE/5HT reuptake (TCADs, SSRIs)
  • dec central sensitization: block VSCC (anticonvulsants) and block NMDA-Glu receptors (ketamine)
  • dec peripheral sensitization: block VSSC (anticonvulsants, local anesthetics)
  • ## emphasis on nonopioids analgesics

Neuro (4 decks)

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