Vlad Neurology Week 5

7/30/2019 Vlad Neurology Week 5

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Neurology week 5

Central visual pathwaysRods and cones in retinaChain of neurons in retina which merge in optic nerve

Optic chiasm optic tracts thalamus optic radiationsPathway terminates in occipital lobe and primary visual cortex

RetinaRods and cones

Located in your neural layerHave photo pigment like Rhodopsin in laminated discsRod are night vision while cones are color visionFovea is surrounded by macula. Are highest regions of visual acuity

Neurons

Neuron 1 = bipolar cell

Neuron 2= ganglionic cellCollect at optic disc forming optical nerve, disc has a blind spotInterneurons are Amacrine cells and horizontal cells

Visual field

Each field has four quadrants Since we have two eyes, fields Overlap

Each retina is also divided into four quadrants Lens causes inversion and right-left reversal of visual fields and retinal

quadrants Optic nerves chasm and tract:

Optic nerve carries signal; macular fibers in centerNasals cross in chiasm, temporals uncrossed

Optic tract: ipsilateral temporal, contralateral nasal: thus each tract carrieseither both left halves or both right halves of vision taking a full binocular

field

Lets full right binocular field to be seen by the left cortex and vice versa

Lateral geniculate body (LGB)Neuron 3 for most fibers from tract. Ones that don't go here go to brainstormfor visual reflexesAfter LGB go to cortex via optic radiations

Optic Radiations:Go thru most posterior part PLIC. Called retrolentiform due to location behind


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lentinform nuTravel pattern: Axons from 2 lower retina quadrants (upper visual fields) make

a loop hugging inferior horn of lat ventricle (Meyer loop) and 2 upper ret quadsgo straight thru parietal lobe to cortex (hence better reaction to things coming

from below?)

Visual cortexReceives input of contralateral part of binocular vision

Axons that went straight go to cuneus (above calcerine sulcus)Axons that looped go to lingual gyrus

Macula represented most posteriorly, peripheral fields anteriorly

Homunculus: macula/fovea gets more brain real estate compared to peripheral Visual perception and initial processing here

Visual association cortexMedial and lateral (mostly) surface of occipital lobe

Subconsciously interprets all major visual stimuliImportant for accommodation reflex

More visual areas:Next step is ventral "what" pathway in temporal lobes: helps identify objectincluding face recognitionOr dorsal "where" pathway via multimodal for motion/object location in visualfield

Lesions of pathway and deficits that arise

Lesions anterior to chiasm will affect only ipsilateral eye, posterior both eyes

Anopsia = loss of vision full field, Hemianoxia=1/2Hemianopsia: bitemporal is both temporal fields hit

quadtantanopsia: 1/4 field affected

Specific deficits:Focal/massive damage to retina:

Scotoma: focal area of impaired vision; can be from multiple causes(diabetic retinopathy, infarct, infections)Papilledema: edema of optic disc from Intracranial pressure, which causescompression of optic nerve by meninges.Massive damage=retinal detachment, full diabetic retinopathy which lead toblindness

Lesions along visual pathways:Optic nerve lesions can lead to anopsia; frequent in MS, happens due toischemia, tumors, trauma, glaucomaChiasm: lesion causes bitemporal hemianopsia due to partial cross, pituitary


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tumors frequently cause this via compressionOptic tract: hit ipsilateral nasal pathway and contra temporal or full contra

1/2 of visual field. Called homonymous hemianopsia; could result fromtumors/ demyelination

PLIC: vascular lesions; same pathology as above but may hit motor and

other sensory as well. Frequently lacunar strokes spare visionTemporal and parietal lobes: temporal lobe hit causes superiorquadrantanopsia while parietal will cause inferior. Tumor or infarct arecommon cause Occipital lobe: cause homonymous hemianopsia with macular sparing incontra half of visual field. No clue why macula spared. During PCAocclusion possible anastomoses with MCA for macular region

Visual reflexesLight reflex

Shining light in one eye causes bilateral miosisAfferent limb: fibers bypass LGB into pretectal area, via barachium of

superior colliculus terminate in pretectal nuclei.Pretectal nu projects bilaterally to para nu of III (EW nu)Efferent limb: III para nu Ciliary ganglion pupil constrictor

Accommodation reflexOccurs when focus on near object after far object; 3 reflexes concurrent

Convergence of both eyes (medial recti of both contract)Miosis

Rounding of lens (via SM of ciliary body contract)Afferent: retinal ganglion/ optic nerveAssociation limb: LGN primary visual cortex Visual association cortexAccommodation center other than pretectal nuEfferent: accom center III nu medial recti/ciliary ganglia andconstrictor papillae and ciliary muscles


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Abnormal pupillary reflexesDamage to optic nerve will result in lost/sluggish reflex when affected eye

stimulated but normal when unaffected eye stimulatedIII nu/nerve lesion causes loss/sluggish in affected eye but normal consensual

reflex in opposite eye. When unaffected eye stimulated it will have normalreflex, but affected eye will have impaired consensual reflexLesions behind optic tract will spare light reflex since they branched off

Pupil reflex lost with intact accommodation in late syphilis.

Serotonin, histamine, GABA, and GlycineSerotonin

Big effects on cardio, GI and respiratory systemsEnterochromaffin cells in gut and platelets have lot of sero; little in brain

High [pineal] and also lots of serotonergic neurons in pons and upper brainstem

Synthesis

TRP have daily rhythmic variation thus 5-HT have circadian rhythm affect onbrain

Catabolism:

5-HT

Melatonin: Induces pigment lightening of skin

Suppress ovulation and controls sleep

Vary during day; mostly in evening

Testing for its use in fixing circadian rhythm disorders

Serotonin receptors14+ identified

G proteins except 5-HT 3 which is Na-ionophoreMescaline and psilocybin r agonists of 5-HT 2A&C thus why they r good

hallucinogens


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Many locations across brain

Neuropharmacology of serotonergic neuronsTRY hydroxylase mutation in PTs with manic-depressive illnessReserpine causes serotonin depletion

LSD is partial agonist of serotonin synapses in CNS

autoreceptors monitor 5-HT releaseSSRI inhibit reuptake like Prozac; Tx depression

OCD may be responsive to SSRI Txhallucinogens associated with 5-HT receptors

Sleep regulation linked to serotonin metabolism

Low 5-HIAA found in aggressive PTsEcstasy causes 5-HT release; reduces 5-HT availability for months and can leadto serious serotonin neuron loss later in life

HistamineMade by mast cells for immune response to allergens systemicallyIn brain made by hypothalamus

Made from histidine directly by histidine decarboxylase Broken down by methyl transferase

Histamine receptors:H-1: bronchoconstrictionH-2: regulate adenylate cyclase, neocortex, HC. Antagonists decrease gastric

acid secretion

H-3: autoreceptors; inhibit and you wake up

H-4: present in leukocytesHistamine pharm

Pharm effects: bronchospasm and hypotension

Alters food H2O intake in hypothalamusH-1 antagonists are sedatives

New antihistamines not sedative since they don't cross the BBBDriving under antihistamine is 2nd most dangerous after DU EtOH

Prolonged use of antihistamines causes AD like symptoms

GABAMajor inhibitory nt discovered at USC

Affected in many diseases like epilepsy, schizophrenia, tardive,Huntington's, and othersFound in Purkinje cells and spinal cord


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Doesn't cross BBB like all other nt'sMetabolism

Linked to Krebs cycleRegulated by decarboxylation of L-glutamic acid by GAC

Glial cells part of GABA metabolism and recycling

ReceptorsGABA-A gated chloride channels are inhibitory; hyperpolarize membranes

Benzodiazepam is agonist, bicuculline, antagonistPentobarbital binds to barbiturate site

Picrotoxin = antidote to barbiturate poisoning

GABA-BUse Second messengers: adenylate cyclase or phosphatidyl inositolMonitor [GABA]baclofen is powerful agonist for GABA-B

Large variety of GABA-A subtypes Subunit structure can change right after acute EtOH intoxication (TGIF party)or after chronic consumptionLow alcohol levels increase affectivity of some GABA receptors

Sobriety pill negates intoxicated behavior by acting on GABA (not FDAapproved)EtOH crosses BBB thus affects NMDA and 5-HT too

Glycine

Major inhibitory nt in brain stem and spinal cord

Used by short axon interneurons

Biosynthesis/ catabolismMajor metabolic GLY doesn't mix with nt GLY

Made from serineRemoved by GLY-transporters

GLY ReceptorCl channel with 5 subunits

Strychnine: GLY-R antagonist, causes convulsions

Picrotoxin, GLY-R inhibitor, is antidote for barbiturate poisoning

Human startle diseaseRare inborn neuromotor disease with exaggerated startle reflexNocturnal convulsions and seizuresDistinct over excitability and diminished inhibition in PT with hyperekplexiaSingle base mutation causing 100x decrease for GLY-Rs


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CNS Micro: meningitis General things

BBB protects CNS, which lacks intrinsic immunity

Scarce Ig's and immune cells in CNS unless infection

Infection of nervous system rare, usually effect of systemic infectionBBB prevents infection getting in but impedes its clearance once in

Immune systemAll antibodies in CSF from serum and at [LOW]

No lymphatics, complement, almost no phagocytes in CNS

Trauma/inflammation allow leak for those to get inPMNs are main WBC in acute bacterial infections of CNS

Mononuclear cells dominant in viral/subacute/fungal infectionsT cells go first then recruits B cells

Cellular structures

No brain-CSF barrier thus in direct contactBut very small gaps between nerve cells so not even virus can squeeze thru

Specialized neural cells in CNS infectionsDifferent neurons have different receptors that may allow viral cell entry

Send toxins and viruses like tetanus and rabies carried by axonoplasmictransport

Direct transfer via surgery, fracture, shunt, or congenital defects for infection

Hematogenous spread occurs for bacteria, fungi, virus, rickettsiae, parasites,builds up to large # of organisms. + some bacteria get rare variants that attackCNS

MeningitisDiffuse infection resulting in inflamed pia-arachnoid meninges

Neonatal bacterial meningitis: E. coli, B streptococcus, or listeria

Neonates are 10% of cases but 50% of deaths of meningitisAdult bacterial meningitis is due to Nisseria meningitidis & Strep pneumoniaeunless trauma/ immunosuppression N. meningitidis is epidemic, others sporadic

Viral meningitis more common but is benign

Clinical manifestation of meningitisHeadache, fever, stiff neck (nuchal rigidity) May reduce consciousness and seizures in kids

Fatal if untreated; cranial nerves palsied and hydrocephalus occur once purulentmaterial collects at base of brainSometimes skin symptoms give away infectious agent


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EXAMINE CSF! important diagnostic toolAcute bacterial infections caused increase PMN cell counts and decrease sugar

content in CSFViruses have less of a mononuclear cell response and CSF protein maybe up but

CSF sugar is normal

Treatment:BBB penetrating antimicrobial agents needed or ~100% fatalityStill relatively high mortality with treatment (15-30%)

Viral meningitis is usually self-limiting and only symptomatic treatment needed

Eye Microanatomy/Lab

the eye overview3 layers

CorneoscleralUveal (iris, ciliary body, choroid)


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RetinaAnterior and vitreous body chambers separated by lens

Chambers:Anterior chamber:

Between cornea and lens

Filled with clear aqueous humor which is secreted by ciliary epitheliumProvides nutrientsSimilar refraction to cornea

Vitreous chamber

Produced by certain retinal cells

Gel made of type II collagen, anchored to basil lamina, ciliary body, lensNo blood vessels or nerves in vitreous

Corneoscleral layer (tunica externa)

ScleraDense connective tissue collagen and some elastic fibers protects eye fromtrauma, and maintains eyeball shapeSite of attachment for extraocular musclesLamina cribosa: plate with holes thru which axons of optic nerve can passthru

Cornea

Transparent, avascular tissueGets nutrients from aqueous humor and tear fluid

Five layers:

Corneal epitheliumBowman's membrane basement membrane corneal epitheliumCorneal stroma bundle of type I and 5 collagen and hydrated groundsubstanceDescemet's membrane basement membrane corneal endothelium Corneal endothelium simple squamous epithelium which controlshydration stroma and has limited proliferative potential

LimbusTransitional zone between cornea and sclera

Increase humor leads from here via trabecular mesh work which merge to formcanal of SchlemmIf canal blocked, pressure increases resulting in glaucoma

Conjunctivamucous membrane that covers surface of anterior eyeball and the eyelidsProduces mucus and tears to lubricate eye + immuno protect


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Lens: 3 componentsLens capsule hypertrophied basal lamina

Subcapsular epitheliumMitotically active cuboidal cells on anterior lens surfaceMake lens capsule and lens fiber precursors

Lens fibers most of lens massLong hexagonal cellsLose nuclei as go internally into lens and become filled with crystallinprotein (gives lens transparency in refractive properties)

no blood or nerves in lens; nutrients from aqueous humorSuspended to the ciliary body by suspensory ligament, Zonule of Zinn

ciliary muscles can control tension of Zonule fibersDistance vision Zonule fibers under tension, Ciliary muscles relaxed

Accommodation Ciliary muscles tighten, Zonule fibers relax

UveaChoroid Heavily vascularized, pigmented connective tissue between sclera

and retinaBruch's membrane Border between choroid and retina

Ciliary body Triangular anterior extension of the choroidStroma Three groups of smooth muscle, 2 controlling zonular fibers, 1controls aqueous humor drainage

Epithelium Non-pigmented, bi-laminar, produces aqueous humor

Iris and pupil: determine amount of light in eye; 4 layersanterior surface Incomplete layer of fibroblastsStroma Connective tissue containing blood vessels, nerves, melanocytes(which determine eye color)Smooth muscle- sphincter papillae muscle medial, constricts pupil; dilatorpapillae dilates pupilEpithelium double layer blocks light so only light coming from pupilpasses thru lens

RetinaNeural retina:

Retina is mostly neurons: five class: photoreceptors, bipolar cells, horizontalcells, amacrine cells, and ganglion cellsPhotoreceptors: 3 parts;

outer segment with horizontal membrane disc stack


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Rods have rhodopsin, discs separate from plasma membrane, replacedCones: continuous plasma membrane discs, not replaced, have opsin

Connecting stalk with ciliumInner segment with organelles

Rods are in periphery, cones concentrated near fovea

Muller cell: glial cell in retinaRetina organized into 9 layers: from outside-inward

Photoreceptor layerExternal limiting membrane

Outer nuclear layer

Outer plexiform layerInner nuclear layerInner plexiform layerGanglion cell layer

Nerve fiber layerInternal Nerve limiting membrane

Retinal pigment epithelium: below 9 neural layers, have melanin granules,

stops light backscatteringphagocytoses parts of outer segment membraneEsterifies vitamin A

Retinal detachment between here and neural retinaSpecialized regions of retina

Optic disc: exit of optic nerve, blind spot

Macula lutea: site of central visionFovea: small depression; highest visual acuity here: only cones here and ininner layers of neural retina


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Neuroanatomy Case pathways

EncephalitisInfection of brain parenchyma

Abscess: focus of purulent infection/ bacterial usually

Brain abscesses develop from contiguous infections by hematogenous spread

(especially CPPD, subacute endocarditis, and cyanotic heart Dz)Mixed flora: strep, S. aureus, enterobacteria, bacterioides commonRarely fungiBrain parenchyma abscess from bacterial seeding of devitalized tissue (loveischemic tissue)Manifested by headache, focal signs, seizures


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If focal signs present, get CT or MRI instead of CSF sampleSeen as hypodense pus surrounded by dense capsule and vascularizationCSF usually sterile

Treated with antibiotics for broad spec if poorly defines area or if well

defined, drain abscess and find out organism to target

Spinal epidural and cerebral/spinal subdurals are emergencies

Spinal epidural: pain along root, paresthesias, then irreversible paraplegiaSubdural Abscess has wide area spread, causes hemiplegia and seizures

EncephalitisInflammation of the brain via wide spread intracellular viral infectionsHerpes simplex and arbovirus cause life threatening infection

Rabies too but insignificant case #Different pathogensis for each virus

Herpes 1&2 cause encephalitisNeonates are mostly HSV2 and full systemic infection tooKids and adults is HSV1 and localized (latent in V ganglion etc.)

Usually goes from face to anterior/middle fossa where it can go to orbitalfrontal or medial temporal lobes where it feasts on your CNS

Arbovirus spread from blood to brain, diffuse infection mainly neurons hitRabies goes from bite site via axonal transport to DRG then to CNS

When it infects limbic system you get rabies behavioral changesPolio selectively hits motor neuron populations hence asymmetric paralysis

Clinical manifestations

HSV1: Focal signs, headache, fever, hallucinations, bizarre behavior, focalseizures, hemiparesis, aphasia (loss of speech)Arbovirus: more diffuse&acute Dz. Loss of consciousness, more seizuresCSF exam in acute encephalitis

RBCs seen, high protein, normal sugar, need to PCR for HSV sinceculture and antibodies are negative early, but IgM for arbovirus in CSF isgood for initial presentation

Electroencephalogram (EEG) good for HSV diagnosis due to slow wavesand spikes in infected temporal lobe

Other infections less usefulCT can also vaguely show but brain biopsy is only definitive Dx

Treatment

Need fast Dx of HSV to reduce mortalitySome Arbovirus can be hit with vaccine or mosquito control

Other virals require supportive care


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Slow and chronic CNS infections and DzChronic infections

Spirochetes: Secondary syphilis: 1.5-3 months after primary infectionBorrelia burgdorferi (Lyme): mild meningitis with ECM rash

RetrovirusesHIV gets into CNS early

Can cause acute meningitis or GBSIn clinical aids can get dementia, myelopathy, pain sense neuropathy

HTLV-1: Caribbean and Japan, passed verticalRare progressive myelopathy if infected late in life

In RT infections, CSF has mild mononuclear cells, elevated protein andIgG

Conventional viruses and chronic DzCan cause chronic dz in CNS. Measles can cause it RARELYProgressive multifocal leukoencephalopathy due to JC papovirusRubella causes chronic encephalitis after congenital infection

Slow infections of nervous system

Predictable incubation periods then they go and resemble acute infections

Prions: 30 year incubationKuruCreutzfeldt-Jacob: mad cow dz; no immune response to prions

Parasites and CNS infectionAcute infection: Malaria (p. falciparum), amebiasis, trichinosis (porktapeworm)Chronic infection: sleeping sickness (African trypanosomiasis), Schistosomajaponicum, toxoplasma gondii, taenia solium (cystocercosis = most common

parasitic neuro dz, and most common cause of hydrocephalus and epilepsy inmany south American and Asian areas)

Pathology of CNS infections

Acute meningitisFast onset, fever, headache, lethargy, altered mental status, neck stiffness. canhave petechial rash. Usually bacterial10-15% mortality rate complications often permanent since CNS doesn'tregenerate Hyperemia (acute congestion) of leptomeningial vessels and edema


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Pus accumulates in sulci. Path slide shows base of brain in pusPus eventually fills entire subarachnoid space

Pus is degenerating PMNs and fibrinFrequent hemorrhagic necrosis found on autopsy

in viral, little pathology, just few mononuclear cells in CNS

Chronic meningitis

Similar symptoms to acute with gradual onset of cranial nerve deficits. LesscommonMost common by TB and crypto, but parasites and viruses can cause too

Usually granulomatous and causes hydrocephalus in immuno competent hostMost delicate nerves and arteries at base of brain so damage there is bad

Thick fibrotic leptomeninges with less purulent exudate than acuteCrypto has mucopolysaccharide capsule positive with mucin stain

Ventricles can become filled with gelatinous substance from fungal capsule

Cerebritis/abscess Papilledema: optic disc compression due to mass in brain or other pressure

increaseRing enhancing lesion could be an abscess

At late stage, abscess gets encapsulated; takes a while in brain due to lowconnective tissue stromaAbscess can rupture into subarachnoid and cause secondary meningitis or into

ventricles, causing purulent ventriculitis

Aspergillus: fungal Cerebritis affecting ppl with low immunity; multiplehemorrhagic necrotic lesions

Parasitic Cerebritis: cystercercosisTaenia solium

Many cysts, seizures occurInflammatory reaction happens when larvae die due to severe immune response,

asymptomatic when they're alive

Viral encephalitis/ encephalomyelitisViral infections have tropism (selective infections for types of CNS cells) andlatency Usually present acutely, infect healthy people, hit either gray, white matter orboth depending on virusMononuclear immune cells in CNS clue for virus

Perivascular cuffs mono nu cells surround vessel in "cuff"


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Microglia nodules: microglia, astrocytes, mono nu's activatedCalled neuronophagia when around dying neuron

HSV1 common cause; has microglial nodules and causes hemorrhagic necrosisof temporal lobes. Hits grey and white matter alike

Rabies have Negri body inclusion (sharp eosoniohilic inclusion in cytoplasm; circle or oval), very testable. Likes medial temporal lobe, hippocampus, andPurkinje cellsPolio takes spinal motor neurons and brainstem outArbovirus: most common cause of epidemic viral encephalitis

Subacute/chronic viral encephalitisPML is opportunistic subacute/chronic hitting white matter, caused by JC virus.Hits when immunity is down, fatal if immunity not reconstituted

Multifocal lesions, softening and discoloration of white matter

Myelin stain shows little myelin in these infectionsAttacks oligodendroglia

HIV can cause encephalitis (HIVE) and dementia

Lot of microglial nodules and multinucleated giant cellsPrions

Mutant protein, turns normal version into mutant via misfolding

Brain looks spongiformed with no inflammatory responses Stupor and ComaCerebral hemispheres and brainstem control consciousness

Reticular activating system (RAS)

Intralaminar nu and reticular nu @ thalamus/diencephalon Pre-aqueductal Gray @ midbrain

Tegmentum (projections from regimental fascicles @ Pons)Levels of consciousness

Alert: normalLethargic/obtunded: can be aroused; if hallucinate, called deliriumStuporous: unresponsive unless heavily aroused, knocks out again

Comatose: unresponsive no matter whatVegetative state: psychologically unresponsive, physiologic only, eyes open

to auditory stimuliDifferential:

Locked in syndrome: stroke of anterior pons; full paralysis but conscious,communicate by blinking


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Catatonia: mute and low motor activityStatus epilepticus: subclinical seizures

Pseudicoma: feigned coma

Clinical assessmentVitals

BP and pulseTemperature: can have hot or cold comasBreathing pattern:

Forebrain: post hyperventilation apneaHypothalamic/midbrain: Central neurogenic hyperventilation/apneusticbreath (pause at full inspiration)Medullary dysfunction: ataxic (irregular) breathing

State of consciousness: assess for aphasia

Pupils: size/reactivity: distinguish b/w metabolic and structural comaDiencephalic: small and reactiveMidbrain: mid position/irregular, fixed, unequal

Uncal herniation: ipsilateral fixed pupil dilationPontine: tiny pupils Medulla: Horner's

Drugs: anticholinergic (large), opiates (small), barbiturate (fixed)Visual fields check

Funduscopic exam: check papilledema and venous pulsations (indicate not high

intracranial pressure)

Eye movements:Check natural position to see any deviationSpontaneous blinking is good (pontine RAS intact)

Oculocephalic reflex: if neck ok, turn head, eyes should move (doll headeye), if damage to MLF, vestibular pathway, no reflex Oculovestibular reflex: cold water irrigation to ear, eyes deviate slowly

toward cold ear and quickly correct. If warm water opposite eyes go awayfrom ear but nystagmus back toward it. No reflex in brain dead.

nystagmus (fast correction): COWS: cold opposite, warm sameCorneal reflex: V and VII

Gag: IX and XMotor response: pain stimuli

Decorticating: arms flexed legs extended: forebrain above brainstem hitDecerebrate: both arms/legs extended: midbrain hit: worst prognosis

Neck stiffness: Burdzinski and Kernigs sign for meningeal infection


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Trauma: racoon eyes (skull fracture)battle sign (hematoma over mastoid, basilar skull break)Rhinirrhea: CSF leak. Check glucose. If + then CSF not nasal fluid

Glasgow coma scale 3-15 (normal)

Eyes 1-4Motor response 1-6

Verbal response 1-5Herniation

Displacement of brain tissue from a compartment

CSF usually displaced first if high ICP, brain nextMassive ICP increase will stop blood flow to brain = deathCT head before lumbar puncture!Herniation follows rostro-caudal pattern

Cingulate gyrus herniation: goes under falx cerebri; asymptomaticUncal herniation: goes under tentorium cerebilli; ispi fixed mydriasis andhemiparesis Tonsillar herniation: brainstem thru foramen magnum: heart/breath fail

Ways to lower ICPElevate headFluid restriction (can give Lasix)Steroid Decadron: good for vasogenic edemaIntubate and hyperventilate with CO2

Neurosurgery: shunt/ craniotomyBarbiturate anesthesia Mannitol: if herniating

Work upCBC, electrolytes, ABG, drug/EtOH/medication list,liver/renal fxn

Neuro imaging: CT/MRILumbar punctureEEG(electroencephalogram)

EP (evoked potentials)

Initial ER treatment for coma: thiamine, glucose, narcan (if opiate overdose),

flumenazil (if Benzodiazepine overdose)Common causes of altered consciousness :Structural or metabolic?

structural: tumor, abscess, stroke, hemorrhage, trauma, hydrocephalus Metabolic: toxins, drugs, nutritional, infection, inflammation, metabolicabnormalities (like hypoxia, renal failure, etc), endocrine, cancer effects andseizures


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Coma prognosisDepends: traumatic coma is better

Longer duration of coma, worse prognosisEEG: spindle coma is fair prognosis. Alpha coma worse

If no EPs in non-traumatic then bad

Brain deathCriteria:

Coma/unresponsiveNo brainstem reflexes

Apnea confirmed by apnea test

Check ABG and CO2, take PT off ventilator on 100% O2 for 8 minutes,check for spontaneous respiration, and ABG and CO2. If no respirationand CO2 above 60mg Hg, apnea +

Exceptions: hypothermia, drug/sedative/etc overdose, reversible medical

conditionCan have some other presentations like spontaneous limb movements, sweat,blush, tachycardia, normal BP/ sudden BP spikes, certain reflexes intact,Babinski reflexRepeat clinical eval in 6 hours advisedConfirmatory tests

Cerebral angiographyEEGEP

Transcranial DopplerTechnetium 99 brain scan (determines if no cerebral perfusion)EP

Depending on age different time points of observation recommendedIf all fails, brain death, discuss organ donation

Mood disordersMood: sustained emotional tone; internal state

Affect: external expression

Mood disorder: prolonged disturbance of mood, disturbs fxn

Major depressive episode: change in feelings, thinking, behavior, bodyHas either or both: constant depressed mood, loss of interest or pleasure inalmost everything everyday (anhedonia) (also lack of motivation)Must have 4:


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Significant unintentional weight/appetite changeInsomnia/hypersomnia

Psychomotor agitation/retardationFatigue

Feeling of worthlessness/ guilt

Diminished ability to thinkRecurrent thoughts of death suicide attempt

2+ week duration (usually 6-13 months)Impaired functioning

Random facts

Any age onset$83 billion loss due to disability2x more in womenDepressed mood vs somatic expression varies by culture. Kids usually

somaticizeIf severe depression, psychosis begins

causes:Bio: possible decrease of neurotransmitters, genetics affecting serotoninuptake, reduced left frontal love activityPsycho

Coping skills/defense mechs make it betterCatasrophize, exaggerate guilt and worthlessnessDepression brought in by stressors like disability or loss of someone close

Social Childhood adversity = susceptibility to depress Poverty, low education, loss of job/home can triggerSometimes no stressor needed

Need to treat with meds, therapy, and removing stressors biopsychosocial!

Bereavement Normal response to death of loved one

mimics depression but temporary

Want to be with person (but not commit/plan suicide to do so)

if crossover to suicide ideation, psychosis, pervasive feeling of worthlessness,then became depressive episode

Adjustment disorder with depressed moodDepressed mood secondary to stressor that causes impairment Doesn't meet criteria for bereavement or depressive episode


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Bipolar disorderBipolar I: manic episode with/without depression

Bipolar II: hypomanic episode w/ major depressionLifetime dz, need meds forever

Late adolescent onset

Bipolar EtiologyBio: 65% heritable aka big genetic component

Responds to antipsychotics, dopamine hypothesisTransduction change due to structural change in neuron membrane

TxMeds

Mood stabilizers like Li, valproic acid, carbamazepine, atypical antipsychotics

Avoiding street drugsConsistent sleep schedule

Family/ individual therapy

Manic episodeMust have: one week + of abnormally elevated/expansive/irritable mood

3 of following:Grandiosity, inflated self esteemDecreased need for sleepTalkativityFlight of ideas

Distractibility Increased goal directed activity

Excessive involvement in risky pleasure activities

Mood disorders secondary to general medical conditions...pretty much every big diseaseSubstance induced mood disorders

Cocaine/meth make you seem manicAlcoholism = depressionMood disorders vs. substance abuse hard to tell since often concurrent, needto treat both concurrently

SuicideAgitation and comorbid anxiety are suicide risk factors

Bipolars have higher suicide than unipolar depression


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Antidepressants and mood stabilizersPsychotherapy: CBT or IPT

1/3 get remission

As effective as antidepressants in mild cases of depression Need PT who can participate

Good for coping strategiesElectroconvulsive Therapy (ECT)

50-70% effective at episode treatment

Memory loss and headache SxGood for major psychotic depression and only option sometimes

Pharmacotherapy1/3 get remission with one antidepressant, Need more trails and meds for

optimal remission rateModulates nt's function; affects G-protein receptors; increases neuronal

repair by CAMP, CREB and BDNFTime course:

1-2 weeks sleep and appetite go up3 weeks energy up4-6 weeks mood and anhedonia improve6-8 weeks for full dose4-9 months @ full dose for all PT

Maintenance for 1-2 years @ full if 3+ episodes or lifetime if old/ 3+episodes in last 5 years

Antidepressants grouped by class (TCA) or by action, selective serotoninuptake SSRI, and monomania oxidase inhibitor MAOI

Main pointsTCA: amitriptyline (Elavil); effective and and inexpensive, can causecardiotoxicity/ heart block. Lethal overdoseSSRI: fluoxetine (Prozac); safe even in overdose; 30-50% sexual side effects

MAOI: phenelzine (Nardil); can't eat aged cheese or red wine w/ this

Sx mechs

5HT2 stimulation causes nausea/diarrhea, sexual disfunction, headacheWeight gain via hypothalamus affectSedation/dizziness: histamine 1R block/ alpha-1 adrenergic R blockDry mouth, constipation: muscarinic/cholinergic block

There are other type of meds with different Sx profiles

mitrazapine (Remeron): causes sedation and high weight gain but low to no


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sexual dysfunction, nausea, headacheBupropion (Wellbutrin): causes insomnia/upset stomach, seizure risk so no

for epileptics or bulimics, low to no sex dysfunction & weight gain (used forsmoking cessation ad ADHD)

Prozac common to give to kids and teens due to safety

Bipolar disorder treatments

Treat with Li or valproateDrug selection depends on many factors

Monotherapy only 50% effective, need combo therapySometimes supplement with atypical antipsychotics as first line moodstabilizersSometimes sedatives also needed

Need to check blood levels for Li and valproate for efficacy/toxicity

monitoringTaken lifelong to prevent bipolar relapseLi

Inhibits excitatory nt'sNarrow therapeutic/toxic rangeWeight gain, polyuria, polydipsiaInteracts with caffeine and ibuprofen

ValproateUps GABA

Wide therapeutic/toxic range

Weight gain, sedation, lethargyInteracts with aspirin, antacids

Other anticonvulsants are also used as mood stabilizers (carbamazepine,

lamotigine, topiramate, gabapentinBipolar depression requires maintenance of mood stabilizer and cautious useof antidepressants (stop if mania starts)

Cervical Fossa and lymphatics of head and neck

LymphaticsUltimately drains into venous system at right lymphatic duct (1/4) andthoracic duct (3/4)Patterns of lymph drainage and node locations important in cancer

Lymph --> lymphatic capillaries --> afferent vessels --> lymph node --> efferent


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vessels --> right lymphatic duct OR thoracic ductH&N lymphatic drainage

H&N lymph nodes clusters are at pericervical collar (junction of head and

neck)

Superficial cervical nodes (neck) course with external and anterior jugular

veinsThese are swollen in infections and clinicians palpate them

From pericervical collar, efferents can drain into both superficial and deepcervical nodes

Deep cervicals found in connective tissue of carotid sheath with the IJDivided into superior and inferior group

Jugulodigastric node: large node on IJ inferior/posterior to digastric muscleJugulo-omohyoid node: on IJV superior to omohyoid tendon

Cancer and lymphaticsTongue cancer is good example of malignancies spreading through lymphaticsCan go bilaterally

Use "en bloc" technique where you remove all connective tissue and part ofjugular. Radical neck dissection to stop spreadRetropharyngeal, pretrachal, and paratracheal nodes drain to deep cervicals

Cervical fascia

Superficial fascia has muscles of facial expression in it.

Deep fascia, delineates neck into compartments

NeckSupportive structures: C vertebrae, hyoid bone, thyroid and cricoid cartilagesMuscles: SCM, traps, supra/infrahyoids, scalenes

Vessels: carotid sheath ones+ branches, subclavian branches (vertebral)

Lymphatics: see aboveOrgans: pharynx, larynx, trachea, thyroid/parathyroid, salivary glands

Nerves: parts of V3, VII, IX, X, XI, XII, brachial plexus roots, phrenic,

sympathetic trunk and cervical ganglionRoot of neck starting at thoracic inlet important clinically since many structuresleave/enter thorax from there3 main neck compartments:

Visceral: anterior part represented by trachea with all organ stuff

Structural/skeletal: cervical spine+associated muscles


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Carotid sheath: carotid, IJ, XAll compartments enclosed by deep fascia, forming cylinders of deep fascia

Investing layerPrevertebral fascia

Pretracheal fascia

Carotid sheathAll structures of neck go in these compartments

Petracheal and prevertebral are inferior to the thorax and have space calledretropharyngeal space between them. Infection can thus spread from adjacent topharynx to superior/inferior mediastinum via this space

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Vlad Neurology Week 5