Week 5 Flashcards
Dura mater
Most superficial covering; double layer of collagenous tissue; forms venous sinuses; adhered to skull
Epidural space
potential space that can fill with blood after skull fracture
arachnoid mater
fibroblasts and meningothelial cells; adhered to dura; villi (granulations) penetrate dural venous sinuses to conduct CSF into circulation
subdural space
potential space between dura and arachnoid maters; veins pass through, can be torn in minor trauma
pia mater
layer of cells tightly adhered to brain surface; anchors strands of arachnoid trabecular
subarachnoid space
arachnoid trabecular passes through; with aging, collagen is deposited; also subject to infection, neoplasm infiltration, and hemmorages
Virchow-Robinson space
perivenular space between arterial tunica and pia; continuous with subarachnoid space
Neuron. Large perikaryon; lots of nissl substance (RER), but abscent at axon hillock; large nucleus with prominant nucleolus and dispersed chromatin
Reactive Astrocytes
Response to brain injury. hyperplasia and hypertrophy
Astrocyte. Glial cell; major function is to wrap foot processes around the basement membrane of blood vessels and non-synaptic parts of neurons–nutrient exchange; short and highly branched in gray matter, sparse and straighter in white matter.
protoplastic astrocyte
capillary processes; heavily stained with GFAP
astrocyte stained for GFAP
(cells around neuron)
oligodendrocytes; myelinate CNS; smalelr, rounder, darker nucleus than astro; 2-3 normally found around neuron (excess is perineuronal satellitosis)
ependymal cells. glial-derived epithelium lining ventricles and spinal canal. no basement membrane. absorptive/secretory/propulsive functions
choroid plexus. gilal-derived secretory epithelium; long microvilli with few cells. many mitochondria, golgi, and basal nuclei
layers of neocortex and motor/sensory attributes
molecular (mostly pi), ext granular, ext pyramidal, int granular, int pyramidal, plexiform. motor areas are thicker, pyramidals more prominant in motor areas vs sensory.
red neurons. response to ischemic injury (12-24 hrs). shrunken soma, eosinophilia, loss of Nissl. nuclei often darker w/o nucleolus.
lipofuscin. normal age-related process of oxidized fatty acid accumulation. don’t confuse with SN, DMX, or locus ceruleus of rostral pons (pigmented areas)
flame-shaped cytoplasmic inclusions = neurofibrillary tangle in AD
Lewy Body inclusions
gliosis
common response to diverse injury. Astrocyte hypertrophy and hyperplasia. increased GFAP, larger cytoplasm
Routes of pathogen entry to CNS
Hematogenous, local extension (paranasal sinus, middle ear), retrograde transport form PNS, direct implantation (trauma, surgery)
most common predisposing factor to CNS infection
immunosuppression!
pachymeningitis
infection of dura
encephalitis
inflammation of brain parencyhma with mononuclear cells (usually viral)
cerebritis
inflammation of brain parenchyma with PMNs (bacterial)
Acute Bacterial Meningitis (Organisms)
Most common CNS infection. (<6mos: GBS; 6mos-60ys: S pneum, N meningitidis, H flu(less); >60ys: S pneum, Listeria)
Bacterial CNS abscesses (sources, organisms, Sx, imaging, path)
Sources: local or hematogenous (2ndry to septic emboli), S aureus, Strep, polymicrobial, present w/ fever and focal deficits related to localization, ring-enhancing lesion, central liquefaction with fibrotic capsule and mass effect.)
Mycobacterial infection of CNS (organism, localization, presentation, path)
TB! (often miliary), TB meningitis affects basal brain with CN involvement, necrotizing granulomas w/ lymphocytes syncytia and fibrosis
neurosyphilis
tertiary disease; presents as meningovascular, parenchymal, or tabes dorsalis; immunosuppression increases risk
neuroborreliosis
Lyme disease; aseptic lymphocytic meningitis; CNVII palsy; encephalopathyw
Asceptic meningitis (organism)
enterovirus in 80%
Acute Viral Encephalitis (organisms, path)
Seasonal: Arbovirus; nonseasonal: HSV, Rabies, CMV; path: perivascular inflamm infiltrate, microglial nodules and neuronophagia, intranuclear inclusions
hemorrhagic necosis of temporal lobes
HSV1
two settings of CNS pathology from CMV
congenital, immunosuppression
Fungal CNS infection general manifestations
Diffuse encephalitis, leptomeningitis, space-occupying lesions, septic infarcts, hemorrhages
aspergillosis (route, presentation, path)
often hematogenous (ACA, MCA pattern); mimics hemorrhagic infarcts; infiltration of blood vessels by hyphae (silver stain), thrombosis and infarct, variable inflammatory infiltrate.
Zygomycosis (presentation, path)
Diabetic ketoacidosis, Rhinocerebral disease; similar to Asper but wider non-septate hyphae
Amebic encephalitis (Organism, tropism, path, source)
Naegleria fowleri; frontal hemorrhagic necrosis with cerebral swelling; unicellular organisms in subarachnoid space with vesicular nucleus and prominant nucleolus; from contaminated water
cysticercosis
ingestion of contaminated pork, caused by Taenia solium, multiple small disseminated cysts, leading cause of epilepsy
CNS infections of immunocompromised host
Crypto meningitis, toxoplasmosis, HIV encephalopathy, progressive multifocal encephalopathy (JC virus)
Cryptococcal meningitis (organism, path, presentation)
Crypto neoformans; pseudocystic dilations of V-R space (“bubbles”) postivie india ink; variable presentation (slow-evolving with remission/relapse)
Toxoplasmosis (type of organism, pattern of infection, path)
obligate intracellular; ring-enhancing brain abscess; best seen with IHC
HIV encephalitis (tropism, path)
less common with HAART; subcortical white matter; widespread low-grade inflammation, multinucleated giant cells, patchy demyelination and variable gliosis.
Progressive Multifocal Leukoencephalopathy (organism, tropism, path)
JC virus, oligodendroglia, ill-definied demyelinating lesions, lipid-laden macrophages, intranuclear inclusions, bizarre astrocytes
early abcess: PMN infiltration
late abcess: PMN debris surrounded by fibroblastic collagenous
Acid-fast stain shows TB organisms
microglial nodules (acute viral encephalitis)
intranuclear inclusions (acute viral encephalitis)
microglial nodule and neuronophagia (acute viral encephalitis)
perivascular infiltrate (actue viral encephalitis)
aseptic meningitis
Negri bodies (circumscribed eosinophilic cytoplasmic inclusions). Rabies
cysticercosis (taenia solium). from ingesting eggs. Parenchymal, meningeal, ventricular, spinal (rare) cysts
naegleria fowleri. Primary amebic encephalitis. Fulminant, acute meningoencephalitis with swelling, hemorrhagic necrossis of frontal lobes. Path: unicellular organisms with vesicular nucleus in subarachnoid space
zygomycosis (mucor). Classically DKA, rhinocerebral disease. wider, non-septate hyphae
silver stain of aspergillus (thin, branching hyphae). Infiltrate blood vessels, causing vasculat thrombosis, hemorrhage, infarct with variable inflamm infiltrate. multiple lesions, early resemble hemorrhagic infarct, form abscesses, rarely fibrous ca[sule.
Direct seeding of cranial cavity results in chronic, localized ingection with fibrosis/granuloma
Glasgow Coma Scale
<9=severe; 9-12 = Moderate; 13-15 = Minor. Motor is predictive of overall score.
management of TBI in the field
Stabilize ASAP (not “scoop and run”). Hypotension/hypoxia bad!
Contact Loading TBI
focal injury –> contusion/hematomas and inertial loading. Animal model: pump fluid into rat brain.
Inertial Loading TBI
Results in Diffuse axonal injury (DAI)–most damaging!
Molecular/Morphological events after TBI
Necrosis/apoptosis (months); Inflammation (good and bad outcomes); Atrophy (year–cortex and hippocampus CA1)
Recovery after TBI
Plasticity (new/stronger synapses) and neurogenesis (hippocampus septal fibers regenerated).
Path of DAI
Axonal bulbs/undulations. Stretch injury breaks MTs. primary mechanical damage, 2ndry chemical damage –> MT catastrophe! –> relaxation of undulations but transport interruption. Taxol can improve by inhibiting axon degeneration
ionic dysregulation in DAI
Massive sodium influx reverse Na-Ca exchanger leading to Ca++ influx. NaCH proteolysis of inactivation gate.
repeat TBI
mild DAI (below threshold for Ca++ influx) predisposes to Ca++ influx on repeat injury
Imaging for TBI
Diffusion tensor imaging
Long-term consequences of TBI
Chronic Traumatic Encephalophaty (after moderate to severe TBI or repetitive mTBI). Amyloid-beta plaques and Neurofibrillary tangles. chronic microgliosis/atrophy of corpus callosum
General rules of head trauma
External lesions not a reliable indicator of deeper lesions.
Lethal lesions of skull/brain may be small or absent.
Linear fracture
contact with flat object…can heal on its own.
compound fracture
associated with scalp laceration
complex fractures
fracture involving multiple bones of skull
depressed fracture
2ndry to small object impact
countrecoup Fracture
located distant from point of injury
Basal/Hinge Fracture
Serious! associated with occipital impact
Hinge: along entire base of skull. Serious trauma
Epidural hemorrhage
Between skull and dura. Arterial bleeding.
Often temporal bone fracture with middle meningeal artery laceration
Results in flat compression of brain and herniation
Subdural hemorrhage
caused by motion of brain wrt to skull/dura and tearing of bridging veins
typically occurs over cerebral convexities
increased risk w/ brain atrophy
often accompanied by subarachnoid blood
“currant jelly” clot
Gray-blue appearance of overlying dura
if not evacuated and patient survives, membrane forms…newly formed vessels susceptible to tear
Contusion
surface injury to brain
laceration
tear of brain
Fracture C/L
at site of fracture; tend to be severe
Coup contusions
Caused by bending/rebounding of skull at site of injury with or without fracture
Moving obhect strujes stationary but movable head
Contrecoup contusions
Distant, usually opposite point of impact.
1. Moving head strikes fixed object (eg ground)
or
2. Impuslive loading – Head set in motion or moving head is stopped without being struck or impacted (eg blow to face)
Most common in orbito-frontal surfaces and temporal poles
Older C/L
golden discoleration (hemosiderin) and tissue retraction. Can cause post-traumatic seizures.
Closed Head Injury
Severe angular acceleration forces
Pedestrian-bicycle/vehicle impacts, helmeted cyclists, shaken babies
Paramedian lesions
diffuse axonal injury, concussion, swelling
Primary pontine trauma
common after motor vehicle accident
~12 hrs : retraction balls and axonal swelling
Abusive trauma in I/C
With/without evidence of trauma
with/without fracture of skull or long bones
shaken baby trauma
often small SDH
spinal cord, root, ganglia trauma
corp cllosum transection
optic nerve sheath hemorrhages
deep galeal or periosteal hemorrhages when head is struck against something
Black Brain
total brain necrosis 2ndry to shock and/or severe concussion
Chronic infant brain damage
extensive necrosis, white matter, hydrocephalus in child surviving abuse.
Choroid Plexus
“Kidney of the brain”: tightly regulates CSF composition. highly vascularized
fenestrated capillaries –> ultrafiltrate –> choroid epithelium (cuboidal glial cells with TJs)
CSF composition
much more stable than blood. less amino acids, K+, glucose. Very little protein. low osmolality
CSF reabsorption
Pressure gradient drives CSF from ventricles to subarachnoid space.
absorbed by arachnoid granulations and villi into superior sagital sinus and spinal veins
(possibly by transctosis of large vacuoles)
4 physiologic roles of CSF
Physical support–reduces effective weight of brain
Protection – shock absorber
supply–brain has strict demands and no supplies
Waste removal
3 features of brain capillaries that contribute to blood-brain barrier
Tight junctions between non-fenestrated capillary epithelial cells
Thick basement membrane
astrocyte endfood
Two CNS barriers
blood-brain: regulated by capillaries
blood-CSF: regulated by choroid plexus
BBB restrictions
can cross: uncharged/lipid-soluble molecules, water, some biomolecules (glucose, amino acids, nucleic acid precursers), some drugs
can’t cross: large charged molecules, many drugs
circumventricular organs
not as subject to BBB since have some interaction w/ blood
pituitary, pineal, subcommissural organ, etc
Lumbar puncture: procedure, contra-indications, complications, gross exam
Subarachnoid space sampling L3/L4 or L4/L5
contra: raised ICP–herniation!
Complications: headache
gross exam: first vial often bloody (traumatic tap)
Cloudy: leukocytosis. bloody: SAH. Orange: high carotine ingestions. Brown: metastatic melanoma. Viscous: metastic mucinous adenocarcinoma. Yellow: billirubin breakdown, remote SAH.
CSF lab findings normal vs bacterial vs viral vs fungal meningitis
normal: glucose 60 mg/dL; protein 30 mg/dL
Bacterial: Pressure inc, glucose <40 (PMN metabolism), WBC >1000 (PMNs), protein >100
Viral: normal pressure, glucose normal, WBC 10-200 (lymphocytes), protein normal
Fungal: variable pressure, glucose <60, WBC 10-200 (lymphos), protein >50
meningitis Sx
fever, headache, altered mental status, stiff neck, photophobia
Bacterial meningitis organisms (by age)
neonates: GBS, E Coli, Listeria
Children and aduls: Strep pneum, Neisseria meningitis, H flu
>60 yrs: Strep pneum, Listeria monocytogenes
Viral meningitis organisms
Enterovirus: seasonal, carried by kids, fecal-oral or respiratory
Herpesviruses: less common but significant morbidity/mortality
Arboviruses: RNA viruses spread by arthropods
HIV-associated meningitis
Fungal: crypto, coccidioides immitis, histoplasma
Bacterial: listeria, treponema pallidum, M TB
viral: CMV, VZV
means for crossing BBB
Attachment/transcytosis of endothelial cells (bacteria)
trojan horse–inside circulating cells
diruption of barrier (trauma/surgery)
seizure, provoked, unprovoked, epilepsy
seizure: sudden and transient dysfunction of part of brain due to excessive discharge
provoked: immediate precipitant (NOT EPILEPSY)
unprovoked: no immediate precipitant
recurren unprovoked = epilepsy
7 classes of CNS tumors
neuroepithelial, cranial/spinal nerves, meninges, lymphomas/haematopoietic, germ cell, sellar tumors, metastatic
importance of histological grading of tumors
predicts biological behavior, influences therapy
types of neuroepithelial tumors
astrocytoma, oligodendroglioma, ependymoma, embryonal, neurocytoma, mixed neuronal-glial
Non-infiltrating astrocytomas
pilocytic astrocytoma: mainly children, rarely progress, better prognosis, 7q34 BRAF mutx
plepomorphic xanthoastrocytoma (PXA)
subependymal giant cell astrocytoma: only in familiar tumor (tuberos sclerosis)
grading of diffuse, infiltrating astrocytomas
Atypia (pleiomorphism, angulated/hyperchromatic nuclei) w/o mitosis = Grade II (diffuse astrocytoma). 75% progression
Atypia + mytosis + foci of increased density/pleomorphism = Grade III (anaplastic astrocytoma) . Almost all progress
Atypia + mytosis + neovascularization or pseudopallisading necrosis = Grade IV (Glioblastoma)
diffuse astrocytoma. scattered, pleomorphic, angulated, hypochromatic nuclei w/o mitoses
gemistocytic variant diffuse astrocytoma (grade II). plump cells with glassy cytoplasm
anaplastic astrocytoma (grade III): atypia + mitoses. foci of increased density/pleomorphism
(tumor type and genetics)
glioblastoma (grade IV astrocytoma): high cellularity, atypia, mitoses, areas of necrosis and neovascularization.
IDH 1/2 = 2ndry GBM. IDH 1 = better prognosis
EGFR = probably primary
TP53 = probably secondary
(tumor type and genetics)
spony-cystic type pilocytic astrocytoma (non-infiltrating).
7q34 BRAF fusion
(tumor type and genetics)
compact type pilocytic astrocytoma (non-infiltrating) with Rosenthal fibers
7q34 BRAF fusion
oligodendroglioma (grading, histology, genetics)
highly infiltrating = always grade II
fried egg and chicken wire
80% 1p/19q loss of heterozygosity (favorable: respond to chemo/rad)
ependymoma (histology, prognosis)
tend to cluster around blood vessels, forming pseudorosettes, prognosis bad for children (brain), OK for adults (spinal)
embryonal tumors (demoraphics, grading, most common type)
children, all grade IV–infiltrative/invasive, medulloblastoma most common
Medulloblastoma (grading, location, histology, consequences of therapy)
All grade IV, arise from cerebellar vermis, well-circumscribed but invasive, densely-packed cells with round/ovoid nuceli and frequent mitoses; homer-wright rosettes ~40% considered signs of differentiation.
neuronal differentiation can be detected with antibody to neurofilament
therapy associated with cognitive impairment
homer wright rosettes (medulloblastoma–differentiated)
dense round/ovoid nuceli = medullablastoma
pseudorosettes surrounding blood vessels = ependymoma
ependymoma
fried egg + chicken wire = oligodendroglioma
tumors of cranial and paraspinal nerves (types)
Schwannomas
Slow-growing Schwann cell neoplasm. Usually benign but effect CN due to compression (displaces normal elements of the nerve).
Most commonly CN VIII, 2nd most common CN V
genetics: NF2 –> bilateral CNVIII schwannoma
Neurofibroma
usualy seen with NF1
infiltrate entire nerve, incorporating axons
technically benign but hard to treat
Dermal–>nodular lesion of skin
meningioma (demographics, cell of incedence, common locations, imaging, histo, immuno)
15% intracranial neoplasms. More common in females, increases with age
arise from arachnoid granulations
convexity, para-sagittal (falx), sphenoid ridge, sella, etc
even enhancement on contrast-MRI
transitional: whorls and cords; psammamatous: whols with psammoma bodies (10 ys post-radiation); fibrous
stain EMA
metastatic CNS tumors (prevalence, common primaries, imaging, prognosis)
15% intracranial neoplasms
lung, breast, skin, kidney, colon
sometimes (?) ring-enhancing
can often be removed, but prognosis depends on location
whorls with psammoma bodies = psammomatous meningioma
whorls and cords = transitional meningioma
General brain tumor incidence
2% malignant neoplasms; 20% in children (2nd to leukemia)
bimodal distribution (<5yo, 45-70 yo)
Males: gliomas and embryonal. Females: meningiomas
tumor type by age/sex
Males: gliomas and embryonal. Females: meningiomas
kids: embryonal/pilocytic astrocytoma
2-34: pituitary and meningioma
34-44: meningioma and nerve sheath
45+: meningioma and GBM
etiology of brain tumors
mostly sporadic/unknown
<5% associated with hereditary syndromes: NF1, NF2, tuberous sclerosis
~10 yrs after X-irradiation (meningioma)
immunodeficiency pre-disposes (AIDS)
Sx of brain tumor
epilepsy (focal or generalized)
focal neurologic deficit
mental changes (variable depending on location eg apathy/depression for frontal lobes)
obstructive hydocephalus –> headache
Sx of Brain tumor due to raised ICP
Headache (postural, nocturnal, early morning)
Vomiting (children)
Papilledema
Clouding of conciousness and coma
Can lead to arterial compression, vascular insufficiency, necrosis
Herniation sites and consequences
Subfalcine (ACA compression/lhemorrhage)
Transtentorial (parahippocampal gyrus)–>Duret hemorrhages in brainstem … Uncal if only the anteromedial part of temporal –> CNIII palsy
Tonsillar–>respiratory arrest
ILAE epilespsy classification (4 items)
MEEE: Mode of onset (focal, generalized)
Epilepsy syndromes (complex of signs that define a recognizable type)
Etiology (genetic, structural/metabolic, unknown)
Evolution (Self-limiting, treatment-responsiveness)
Generalized seizures
no motor asymmetry–bilateral
EEG symetrical
rapidly engage bilateral networks (corical, subcortical, both)
lots of focal-spreading seizures look generalized
diverse: absence, myoclonic, tonic-clonic, tonic, clonic, atonic
Focal seizures
Arise within networks limited to one hemisphere, preferential propogation
With or without impairment of awareness
Can evolve to bilateral convulsive
asymmetrical EEG
Frontal lobe onset focal seizure
Motor strip-clonic shaking of contra limbs
Anterior to motor strip near midline–complex, bilatteral hypermotor activity
Broca’s – expressive language dysfunction
Fronto-polar – arrest of activity, hypomotor (can look like absence seizure). Can progress to motor faster than temporal.
Temporal lobe onset focal seizure
characteristic look:
aura, arrest of activity, unresponsiveness, motor automatisms(“pointless fiddling”)!!
Parietal lobe onset focal seizure
difficult to localize. often clinically silent then present with lobe of propogation
Occipital lobe onset focal seizure
Visual signs (positve or negative)
often present as temporal
Epilepsy etiology
Genetic (presumed or proven) – often manifest 5-20 yo
Structural/metabolic (aquired: stroke, trauma, infection, tumor; developmental: malformations of development)
Unknown
epilepsy Tx
60% respond to first or second AED.
Then surgical assessment or rational duotherapy
Different Rx for focal vs general–importance of characterizing!
long-term consequences of epilepsy
Even if controlled, comorbid with many psychiatric and social problems–unplanned pregnancy, repeated grades, behavioral problems.
general seizure pathophys
disruption of excitiation/inhibition balance
increased excitation: mossy fiber sprouting, changes in EAA receptors, presynaptic changes
decreased inhibition: GABA receptor, loss of interneurons, change of interneuron activity.
epileptogenesis model
insult + genetics/age etc –> acute damage –> progressive damage –> hyperexcitability –> seizures –>progressive damage
focal seizure pathophys
Paroxysmal depolarization shift
sustained repetitive firing mediated by v-gated Na+ channels (can occur w/o Ca++ current)
paroxysmal depolarization shift
functional unit of focal seizure
prolognue Ca-dependent depolaruzation leading to sodium-mediated action potentials
prominant hyperpolarization after due to calcium-dependent K channels
Generalized seizure mechanism
disturbance in thalamo-cortical network. T-type / Na+ channel spike-wave pattern.
age-related pathophys of seizures
infants are in hyper-excitable state
intracellular Cl- is high during development –> GABA is excitatory (switch from NKCC1 activity to KCC2 changes this)
NMDA develop before AMPA
GDPs (GABA-mediated)
General principles of pharmacological Tx of seizures
treats symptoms, not underlying epileptic condition
Does not prevent epilepsy
Maximize QOL: minimize seizures and adverse drug effects
Types and mechanisms of AEDs
Na+ channel blockers – block repeptitive firing only. used for focal epilepsies
GABA enhancers – replace “lost” inhibition. Barbituates and benzos
Glutamate modulators – EAA antagonists
Ca++ channel blockers – modulate T-type Ca++
Syaptic transmission modulators – GABA reuptake inhibitors, GAD activators etc
MS definition and presentation
diagnosis of exlusion
primary demyelinating disease of CNS characterized by episodic neurological dysfunction and may result in progressive course of defects
Problems of white matter tracts – optic neuritis, UMN weakness/uncoordination, vertigo, speech, gait, bladder spasticity, INO
sensory dyesthesia
waxing/waning
pathogenesis of MS
immune activation of T cells (CD8) in periphery, migration to CNS (molecular mimicry, self antigen)
neuroinfalmmation, oligodendrocytes targetted
demyelination and axonal degerneration
gross brain atrophy
general criteria for MS diagnosis
Lesions disseminated in time and space
T2/FLAIR hyperintenities and T1 “black holes”: subacute/chronic lesions (eg Dawson’s Fingers)
Gd-enhancing lesions on T1: markers for inflammation and BBB breakdown. acute lesions.
Also oligoclonal IgG bands in CSF
DMTx for MS
suprression of relapses is goal
All act in periphery to prevent CNS entry/activation of T cells and monocytes
Tysabri: anti-T cell integrin mab
DDx excessive sleepiness
Narcolepsy, sleep apnia, insufficient sleep, medication effect
DDx insomnia
Mood disturbance, circadian rhythm disturbance, RLS
DDx unusual movement/behavior during sleep
Parasomnia emerging from REM or non-REM sleep, nocturnal seizure, movement disorder
Narcolepsy tetrad
hypersomnolence
cataplexy
hypnogogic/hypnopompic hallucinations
sleep paralysis
(sleep quality often impaird also)
Narcolepsy pathogenesis
deficiency in hypocretin/orexin (responsible for sleep/wake switch)
REM sleep behavior disorder
dissociated state: dream enacting behavior, increased tonic or phasic EMG in REM sleep, absence of epileptiform activity
REM sleep Behavior Disorder etiology/associations
normally, pon neurons inhibit motor
idiopathic, narcolepsy, neurodegenerative (PD, LBD), medications
RLS vs PLM
RLS = awake sensory phenomenon with volitional motor response
PLM = involuntary sleep-related motor phenomenon
most RLS patients have PLM, but not vice-versa
RLS pathophys
impairment of dopamine transmission?
iron def, pregnancy, renal failure
basic biology of circadian clock
SCN = master clock
VLPO = switch (inhibits monoamine systems)
pineal gland secretes melatonin
REM sleep
v different fro SWS. EEG looks almost like awake EEG but muscle atonia
