11.3 Neurology Flashcards
Where do PNS neurons originate from embryologically?
Neural crest
Where do oligodendroglia originate from embryologically?
Neuroectoderm
Where do CNS neurons originate from embryologically?
Neuroectoderm
Where do Schwann cells originate from embryologically?
Neural crest
Where do microglia originate from embryologically?
Mesoderm
Microglia, like Macrophages, originate from the Mesoderm.
Where do astrocytes originate from embryologically?
Neuroectoderm
Where do ependymal cells originate from embryologically?
Neuroectoderm
Ependymal cells make up the inner lining of ventricles, and make CSF)
What neurological structures originate from Neural crest cells?
Schwann cells
PNS neurons
What neurological structures originate from Neuroectoderm?
CNS neurons
Ependymal cells
Oligodendrocytes
Astrocytes
What neurological structures originate from Mesoderm?
Microglia
T/F Neurons do not divide in adulthood.
True. Neurons comprise the nervous system and are permanent cells, which means they don’t divide in adults.
T/F Neurons have prominent nucleoli.
True. Neurons are large cells with prominent nucleoli.
Where is nissl substance located in neurons?
Nissl substance = RER of neurons. It is located in the cell body and the dendrites, but NOT in the axons.
What is Wallerian degeneration?
Axon injury leads to neuron degeneration, which starts at the point of injury and spreads distally.
What are astrocytes and what do they do?
Star-shaped type of glial cell. Maintain the blood-brain barrier. Provide physical support and repair, K+ metabolism, and removal of excess neurotransmitters (take up glutamate and GABA). They also regulate pH/ion balance.
Cause reactive gliosis in response to injury (repair following trauma).
What is the marker for astrocytes?
GFAP.
GFAP is also the marker for glioblastoma, since astrocytes are a type of glial cell.
What is reactive gliosis?
Repair by astrocytes following a trauma.
The astrocytes proliferate and swell, leading to fibrosis. The fibrosis forms a glial scar in place of the damaged neurons.
What are microglia?
CNS phagocytes (the macrophages of the CNS).
They are mesodermal in origin (like macrophages).
They have small irregular nuclei and little cytoplasm.
When there is tsu dmg, the microglia become large ameboid phagocytic cells.
They make cytotoxins and neurotoxins like NO and glutamine which mediate inflam.
How are microglia stained?
They are not discernable in Nissl stains- use lectin to stain them brown.
What happens when microglia become infected w HIV?
They fuse to form multinucleated giant cells in the CNS.
What are oligodendroglia?
Myelinating cells of the CNS- each oligodendroglial cell myelinates up to 30 (!) CNS axons.
These are the predominant type of glial cell in white matter.
How do oligodendroglia stain?
Nissl stain: small nuclei w dark chromatin and little cytoplasm.
H&E stain: fried eggs
What cells look like fried eggs on H&E?
Oligodendroglia
Koilocytes (HPV)
Seminoma
Schwann cells
Myelinating cells of the PNS. Each schwann cell only myelinates one axon.
Promote axonal regeneration.
Derived from neural crest.
Acoustic neuroma
Type of schwannoma, usu located in the internal acoustic meatus (CN VIII)
In what disease are there bilateral acoustic schwannomas?
NF-2
What kind of cells are destroyed by MS?
Oligodendrocytes! (of the CNS)
What pathway do responses to mechanical stimuli take to get to the brain?
Mechanical stimuli –> afferent neurons in SC –> either dorsal column/medial lemniscus or in the spinothalamic tract.
What are the types of free nerve endings?
Free nerve endings are aka Ruffini endings.
A-delta: feel pain; fast myelinated fibers (fast first pain)
C - hot/cold, blunt trauma; slow unmyelinated fibers (longer lasting dull 2nd pain)
Where are free nerve endings (Ruffini endings) located, and what senses do they transmit?
All skin, epidermis, and some viscera
Transmit pain (A-delta endings ) and temp (C endings)
Where are Meissner’s corpuscles located and what senses do they transmit?
They are large, myelinated fibers located in glabrous (hairless) skin and dermis.
Transmit position sense and dynamic fine touch (manipulation). They adapt quickly.
Where are Pacinian corpuscles located and what senses do they transmit?
Large myelinated fibers- these are the ones that look like a fingerprint.
Located in deep skin layers, ligaments, and joints. Subcutaneous.
Transmit vibration and prs.
Where are Merkel’s disks located and what senses do they transmit?
Large, myelinated fibers located in hair follicles.
Transmit position sense and static touch (sharp edges, textures). They adapt slowly.
Also sense vertical indentation into skin.
What are the peripheral nerve layers?
Endoneurium- single nerve fiber
Perineurium- permeability barrier, surrounds a fascicle of nerve fibers; must be rejoined in microsurgery for limb reattachment
Epineurium- dense CT that surrounds entire nerve (fascicles + blood vessels)
Which layer of the peripheral nerves is most difficult for drugs to cross?
Perineurium (permeability barrier)
What is the main excitatory NT of the brain?
Glutamine
What is the main inhibitory NT of the brain? What other AA does it come from, and what’s required to make it?
GABA
Glutamate –> GABA, and Vit B6 is required for this.
What is the main inhibitory NT of the SC?
Glycine
Where is NE made?
Locus ceruleus (mainly) also, reticular formation and solitary tract
Where is Dopamine made?
Ventral tegmentum and SNc
Where is 5-HT made?
Raphe nucleus
Where is ACh made?
Basal nucleus of Meynert
In what dz does the Basal nucleus of Meinert degenerate?
Alzheimer’s dz
Where is GABA made?
Nucleus accumbens
What are the parts of the Reticular Activating System and what does it do?
Reticular Formation Locus ceruleus Raphe Nuclei It mediates consciousness and attentiveness (Lesions to RAS cause coma)
What feelings are propagated by the:
Locus ceruleus?
Nucleus accumbens and septal nucleus?
LC- stress and panic
NA and SN- reward center, pleasure, addiction
NT chgs in anxiety
Increased NE
Decreased 5-HT
Decreased GABA
NT chgs in depression
decreased NE, decreased 5-HT
NT chgs in Huntington’s
decreased GABA
decreased ACh
How do ACh levels change in REM sleep?
They decrease
In what dz’s/states does NE increase?
Anxiety
Mania
Amphetamine/Cocaine use
How does dopamine chg in Parkinson’s?
It decreases
What 3 structures form the BBB?
- Tight jns bt non-fenestrated capillary endothelial cells
- BM
- Astrocyte processes
Other than the BBB, what other blood/structure barriers exist?
Blood-testis barrier
Maternal-fetal barrier (placenta)
What substances cross the BBB by carrier-mediated transport?
Glucose and AAs
they cross slowly!
What substances cross the BBB by diffusion?
Nonpolar/lipid-soluble substances
(they cross rapidly)
many anesthetics are lipid-soluble and therefore can cross. the more lipid soluble, the more potent.
What areas of the brain have no BBB, and what does this allow?
Area postrema- vom after chemo
OVLT- osmotic sensing
The regions just have fenestrated capillaries.
They allow molecules from the blood to affect brain fn, or oppositely, neurosecretory products to enter circulation (eg post pit –> ADH –> blood)
Where is the area postrema?
Caudal wall of 4th ventricle in medulla
When can the BBB be breached?
Brain tumor/neoplasm
Infection
Infarction
These destroy endothelial cell tight jns, which leads to vasogenic edema. (Edema can be seen on imaging.)
What are the functions of the hypothalamus?
TAN HATS: Thirst/water balance Adenohypophysis control Neurohypophysis rls's hormones from hypothal Hunger Autonomic regulation Temp regulation Sexual urges
What are the inputs to the hypothalamus?
OVLT (senses osmolarity chgs) Area postrema (responds to emetics)
What part of the hypothalamus makes ADH?
SON- supraoptic nucleus
ADH makes the kidneys absorb more water
What part of the hypothalamus makes Oxytocin?
PVN- paraventricular nucleus
Oxytocin causes smooth musc contraction in the uterus/breast
What does the lateral area of the hypothalamus do?
Causes hunger
If it’s destroyed, no hunger, so anorexia, FTT in infants.
What does the Ventromedial area of the hypothalamus do?
Causes Satiety.
Destruction, no satiety, so hyperphagia.
Destruction can be caused by craniophryngioma.
What effect does leptin have on the hypothalamus?
Leptin inhibits the lateral area (hunger)
Leptin stimulates the ventromedial area (satiety)
Easy to remember if you know that leptin comes from fat cells. Fat –> Leptin –> don’t eat more (suppress Lateral/hunger) + do feel full (stimulate Ventromedial/satiety)
What does the anterior hypothalamus do?
Cooling
pArasympathetic
it detects increased body temp
A/C = anterior cooling
What does the posterior hypothalamus do?
Heating
sympathetic
it conserves heat
What does the septal nucleus of the hypothalamus do?
Sexual urges
What does the SCN of the hypothalamus do?
Circadian rhythm
SCN is right about the optic chiasm.
What part of the hypothalamus regulates the PNS?
Anterior hypothal
and preoptic nuclei, which is part of the ant hypothal
What part of the hypothalamus makes ADH to regulate water balance?
SON
What part of the hypothalamus will cause hyperthermia if destroyed?
Anterior hyperthal (and preoptic nuclei) These are responsible for cooling. So no Ant hyperthal --> no cooling --> hyperthermia
What part of the hypothalamus regulates the SNS?
Posterior hypothalamus (and lateral nuclei)
What part of the hypothal gets input from the retina?
SCN
What part of the hypothal mediates oxytocin production?
PVN
What part of the hypothal is responsible for sweating and cutaneous vasodilation in hot temps?
Anterior hypothal (and preoptic) Anterior does cooling! (A/C)
Destruction of which part of the hypothal causes neurogenic DI?
SON (bc it makes ADH)
What part of the hypothal causes eating when stimulated, and starvation when destroyed?
Lateral area (mediates hunger)
Destruction of which part of the hypothal results in inability to stay warm?
Posterior hypothal (Responsible for heating)
What part of the hypothal regulates rls of gonadotropic hormomes (LH, FSH)?
Preoptic nucleus
What part of the hypothal releases hormons affecting the ant pit?
Arcuate nucleus
What part of the hypothal is responsible for shivering and decreased cutaneous blood flow in the cold?
Posterior hypothal (and lateral nuclei) Posterior does warming- these are warming activities!
If this part of the hypothalamus is destroyed, savage behvr and obesity result.
Ventromedial area (controls satiety.) No VM --> no satiety, so hyperphagia.
From where is the posterior pit derived embryologically?
Neuroectoderm.
Post pit = NEUROhypophysis, which is from the NEUROectoderm.
What are the inputs to the posterior pit?
Receives hypothalamic axonal projections from the supraoptic nuclei (ADH) and the paraventricular nuclei (oxytocin).
It releases the hormones in response to stimuli.
What are the major parts of the thalamus?
VA VL VPL VPM Pulvinar LGN MGN Anterior nuclear group Mediodorsal nucleus
What kind of info does the thalmus receive, and where does it send the info to?
Gets ascending sensory info
Relays it to the cortex
What info comes into the VPL (and via where), and where is the info sent to?
VPL = body sensation.
The spinothalamic tract carries Pain/Temp to the VPL, and
The dorsal columns (medial lemniscus) carry Prs/Vibration/Touch/Proprioception to the VPL.
The VPL sends all of these to the primary somatosensory cortex
What info comes into the VPM (and via where), and where is the info sent to?
VPM = face sensation (put Makeup on your face- vpM) The trigeminal (CN 5) and gustatory pathway carries face sensation and taste to the VPM The VPM sends this info to the primary somatosensory cortex.
What kind of info do the ventral anterior and ventral lateral thalamic nuclei receive?
VA and VL get motor info.
Note that in the thalamus, motor (VA, VL) is anterior to sensory (VPL, VPM), just as in the cortex.
What info comes into the LGN (and via where), and where is the info sent to?
The optic nerve (CN 2) sends vision info to the LGN. (lateral = light)
The LGN then projects via optic radiations to the occipital cortex (to the calcarine sulcus- this is where the primary visual cortex is located!)
What info comes into the MGN (and via where), and where is the info sent to?
The superior olive and the inferior colliculus of tectum send auditory info to the MGN. (medial = music)
The MGN sends this info to the auditory cortex of the temporal lobe.
What is the blood supply to the thalamus?
P-Comm
PCA
ICA (anterior choroidal arteries)
What part of the thalamus communicates with the prefrontal cortex? What happens if it’s destroyed?
Mediodorsal nucleus
Memory loss if destroyed
What part of the thalamus sends info from the cerebellum (dentate nucleus) and basal ganglia to the motor cortex?
VL (ventral lateral)
What part of the thalamus sends info from the basal ganglia to the prefrontal, premotor, and orbital corticies?
VA (ventral anterior)
What part of the thalamus sends info from the mamillothalamic tract to the cingulate gyrus (part of the Papez circuit)?
Anterior nucleus
What part of the thalamus integrates visual, auditory, and somesthetic inputs?
Pulvinar
What does the cerebellum do, generally?
Integrates sensory info from both brain and SC
Coordinates smooth motor mvmts
What are the input nerves to the cerebellum?
Climbing and mossy fibers
Does the cerebellum receive ipsilateral or contralateral input? From where?
Both!
Gets contralateral cortical input (via middle cerebellar peduncle)
Gets ipsilateral proprioceptive info (from the inferior cerebellar peduncle.
What is the output pathway from the cerebellum to the cortex?
Cerebellar cortex sends Purkinje fibers to the deep cerebellar nuclei (D, E, G, F). The nuclei send outputs via the SCP (superior cerebellar peduncle) to the cortex. Note that the fibers cross(!) in the SCP, so the output is going to the contralateral side (as compared to where it came from in the cerebellum).
What are the deep nuclei of the cerebellum?
Lateral to medial: Dentate Emboliform, Globose Fastigal "Don't eat greasy foods"
The emboliform + globose are together referred to as the interposed nuclei.
What does the lateral cerebellum control?
Voluntary movement of extremities
What does the medial cerebellum control?
Balance
Trunkal coordination
Ataxia
Propensity to fall toward injured (ipsilateral side)
What does the vermis control?
Trunkal coordination
What does the intermediate cerebellum control?
limb coordination
Do the cerebellar hemispheres mediate motor movements of the body on the ipsilateral or contralateral side? Why?
Ipsilateral side!
Bc the fibers cross two times:
1. Through SCP
2. Pyramidal decussation of the corticospinal tract in the medulla.
Note: if you are just talking about info going from cerebellum to cortex, it is contralateral, bc the info crosses when going thru the SCP.
if you are talking about info going to the body, it is the ipsilateral side of the body. cerebellum to cortex crosses when going thru SCP, then cortex to body crosses when going thru the medullary pyramids.
What are the three main regions of cerebellum?
- Spinocerebellum (vermis + paravermal regions/intermediate hemisphere) is most medial
- Cerebrocerebellum (lateral hemispheres)- this is lateral
- Vestibulocerebellum (flocculonodular lobe + vermis)- this is underneath
Where do the regions of cerebellum project to (which deep nuclei)?
Spinocerebellum (vermis + paravermal/intermediate hemisphere) –> fastigial and interposed (globus + emboliform)
Cerebrocerebellum (lateral hemispheres) –> dentate
Vestibulocerebellum (flocculonodular lobe + vermis) –> dentate
What structure provides the major output pathway of the cerebellum?
SCP (aka brachium conjunctivum)
it goes to the contralateral Vl of the thalamus
If there was a lesion on one side of a cerebellar hemisphere, motor control on which side of the body would be affected?
Ipsilateral to the side of the lesion.
Cerebellum goes to the contralateral thalamus (via SCP, where it crosses), then that goes to the cortex, then to the corticospinal tract- which crosses in the medulla (in the pyramids) and goes to the contralateral side to the cortex.
2 crosses = ipsilateral side.
If there is dmg to the spinocerebellum, what will happen?
Spinocerebellum = vermis + paravermis/intermediate hemispheres). Dmg will cause: Postural instability Slurred/slow speech Hypotonia Pendular knee jerk reflexes
What sx are seen in anterior lobe (anterior vermis) syndrome? What is most common cause?
The most anterior part of the vermis = legs, so ataxia, dystaxia of legs, even when trunk is supported –> broad based, staggering gait.
Caused by chronic alcohol abuse –> thiamine deficiency –> degeneration of cerebral cortex, starting at anterior lobe.
What happens if the cerebrocerebellum (lateral hemispheres) is dmgd?
Lack of coordination of voluntary mvmts (both timing and rate)
Delays in initiation of mvmt, trouble stopping mvmt
Dysmetria (can’t control distance/speed/power of mvmt)
Intention tremor
Test these by hand flipping on thigh; finger to nose.
What is the difference b/t essential tremor, resting tremor, intention tremor?
Essential- occurs w mvmt and at rest; fam hx of tremor
Resting- disappears w voluntary mvmt; basal ganglia lesion; a/w Parkinson’s
Intention- only appears w voluntary mvmts (not at rest); a/w cerebellar dmg
Features and RX for essential tremor
Rapid fine tremor of head, arms, hands, voice
50% hv fam hx of tremor
Occurs w mvmt and at rest
Rx: beta-blocker (propranolol), primidone (anti-convulsant), clonazepam (benzo), or alcohol (pts self-medicate)
What happens if there is dmg to the vestibulocerebellum (vermis + flocconodular lobe)?
Disequilibrium- difficulty in maintaining balance
Abn eye mvmts (eg cerebellar nystagmus, more pronounced when pt looks to side of lesion)
Most common cause of dmg to the flocconodular lobe?
Medulloblastoma in childhood
What are the parts of the limbic system?
cingulate gyrus septal nucleus hippocampus fornix mammillary bodies
What does the limbic system do?
5 F's Feeding Fleeing Flighting Feeling Fucking
What does the basal ganglia do?
Collection of structures that are imp for voluntary mvmt and making postural adjustments.
Receives input from cortex, provides negative feedback to cortex to modulate mvmt.
What are the 2 main pathways of the basal ganglia?
Direct/excitatory pathway- promotes movement
Indirect/inhibitory pathway- inhibits mvmt.
What are the structures of the basal ganglia?
Striatum (putamen-motor + caudate-cognitive) Globus pallidus (GPe + GPi) Substansia nigra (SNc + SNr) STN (Note: lentiform = putamen + GP)
Putamen (motor) Caudate (cognitive) GPe: globus pallidus externa GPi: globus pallidus interna SNc: substansia nigra pars compacta SNr: substansia nigra pars reticulata STN: subthalamic nucleus
What are the two dopamine receptors of the basal ganglia?
D1 receptor- excitatory
D2 receptor- inhibitory
What happens when dopamine binds to D1?
To D2?
D1: There is mvmt.
D1 excites the direct pathway –> mvmt
D2: There is also mvmt
D2 inhibits the inhibitory pathway –> mvmt
So ultimately, BOTH cause mvmt! Imp!
What does the STN do to the GPi?
STN stimulates the GPi
What does the GPi do to the thalamus?
GPi inhibits the thalamus
What does the GPe do to the STN?
GPe inhibits the STN
Does the GPi inhibit or facilitate mvmt?
GPi inhibits mvmt (bc it inhibits the thalamus)
Does the striatum (putamen + caudate) inhibit or facilitate mvmt?
Striatum facilitates mvmt.
Does the GPe inhibit or facilitate mvmt?
GPe facilitates mvmt.
Does the STN inhibit or facilitate mvmt?
STN inhibits mvmt.
Does the SNc inhibit for facilitate mvmt?
SNc facilitates mvmt.
Explain the direct pathway (from the cortex)
Cortex stimulates striatum (putamen+caudate) using glutamate.
Striatum inhibits GPi (and SNr) using GABA and substance P.
GPi inhibits the thalamus (but here it doesn’t, since the striatum is inhibiting GPi)
Thalamus (which is uninhibited) stimulates cortex.
So, Direct pathway = mvmt.
Explain the indirect pathway (from the cortex).
Cortex stimulates striatum (putamen+caudate) using glutamate.
Striatum inhibits GPe using GABA and enkephalin.
GPe inhibits the STN (but here it doesn’t, since the striatum is inhibiting GPe)
STN (which is uninhibited) stimulates GPi.
GPi inhibits the thalamus.
Thalamus can’t stimulate cortex bc it’s inhibited.
So, indirect pathway = no mvmt.
Note: D2 receptors inhibit the indirect pathway, causing mvmt.
In Parkinson’s, there is decreased mvmt. Using the direct and indirect pathways, explain why.
Loss of dopamine in Parkinson’s means nothing binds to D1, so there is no stimulation of the direct pathway (by dopamine, that is. there will still be stimulation by the cortex.)
The direct pathway = mvmt. No dopamine to stimulate the direct pathway = less mvmt.
Loss of dopamine in Parkinson’s means nothing binds to D2, so there is no inhibition of the indirect pathway.
Usually the indirect pathway = no mvmt, but dopamine binding to D2 inhibits the pathway, causing mvmt.
If there is no dopamine to bind to D2, there will the the usual indirect pathway- which means no mvmt.
In both cases, there is less mvmt with less dopamine.
Which arteries supply the basal ganglia?
Lenticulostriate arteries.
They are v fragile, called “arteries of stroke”
Come from the MCA.
What are the most common sites of hypertensive hemorrhage?
Basal ganglia and thalamus.
What is Parkinson’s dz caused by?
Degenerative disorder of CNS a/w Lewy bodies (intracellular inclusions md of alpha-synuclein) and with depigmentation of the SNc (substansia nigra pars compacta) d/t loss of dopminergic neurons.
Depigment bc melanin is a precursor to dopa)
Rare cases linked to exposure to MPTP, a contaminent in illegal drugs.
Parkinson’s = excess cholinergic activity + loss of dopaminergic neurons
Sx of Parkinson’s
TRAP: Tremor (at rest, pill-rolling) Rigidity (cogwheel) Akinesia (can't start, can't stop, take more steps when turning) Postural instability (stooped)
It’s a bradykinetic mvmt disorder.
What dz looks similar to Parkinson’s?
Wilson’s dz can cause Parkinsonian sx d/t Copper accumulation in the putamen.
List the main drugs used to treat Parkinson’s.
BALSA: Bromocriptine Amantidine Levodopa (with carbidopa) Selegiline (and COMT inhibitors) Antimuscarinics (esp Benztropine, park your Benz)
For essential or familial tremor, use a B-blocker (eg propranolol)
Bromocriptine
Dopamine agonist used in Parkinsons. non-ergot.
Also used to stimulate the tubero-infundibular pathway (another dopaminergic pathway which regulates prolactin).
What Parkinson’s drugs are similar to Bromocriptine?
Other drugs that agonize dopamine receptors (so they are dopamine receptor agonists):
Pergolide (ergot, partial agonist)
Pramipexole (non-ergot)
Ropinirole (non-ergot)
Non-ergots are preferred (Bromocriptine is a non-ergot)
Amantidine
Parkinson’s drug that increased dopamine rls.
In the past, used as an antiviral against influenza A and rubella (now there is resistance)
Toxicity = ataxia
L-dopa (levodopa) and carbidopa
Drug of choice for Parkinson’s- increases level of dopamine in the brain.
Unlike dopamine, L-dopa/carbidopa can cross the BBB, and once inside the CNS is converted to dopamine by dopa decarboxylase.
Toxicity: arrhythmias from peripheral conversion to dopamine. If used long-term, can cause dyskinesia after admin and akinesia b/t doses.
Why is carbidopa given along with L-dopa (levodopa)?
Carbidopa is a peripheral decarboxylase inhibitor- so it makes sure that there are less peripheral side effects and that the bioavailability of L-dopa is increased in the brain (rather than in the periphery).
What Parkinson’s drugs prevent the breakdown of dopamine?
Selegiline (selective MAO-B inhibitor)
Entacapone
Tolcapone (COMT inhibitor)
Selegiline
Selective MAO-B inhibitor- it preferentially metabolizes dopamine before NE and 5-HT, so the availability of dopamine is increased.
Used along w L-dopa to treat Parkinson’s, but it may enhance the adverse effects of L-dopa (arrhthymias, dyskinesia, akinesia)
Benztropine
Antimuscarinic used for Parkinson’s (park your benz)
It improves tremor and rigidity
Doesn’t really help the bradykinesia tho.
What are the surgical treatments for Parkinson’s?
Lesion the STN
Deep brain stimulation to the STN (this decreases mvmt inhibition, so it facilitaties mvmt.)- don’t be confused by the word stimulation. DBS knocks out the STN (it over-stimulates it)
Hemiballismus
Sudden, wild flailing of one arm (+/- leg)
Happens d/t a contalateral lesion of the STN (eg lacunar stroke in pt w Hx of HTN)
Usually thalamus is inhibited by GP, but when the STN is lesioned there is no inhibition.
Hemi-ball-isitic = half ballistic (throwing a baseball)
If there is wild flailing of the right arm, where is the hemiballistic lesion?
Contralateral STN- in this case, on the left.
Huntington’s Dz
Auto-dom trinucelotide repeat CAG
On Chr 4 (Hunting 4 food)
Neuronal death via NMDA-R binding and glutamate toxicity (NMDA is the glutamate receptor).
Get chorea, depression, progressive demenita.
Onset 20-50yo
Loss of ACh and GABA.
100% penetrance- all individuals w gene will develop it
C’s: chorea, crazy (dementia), CAG repeat, Chr 4, caudate degeneration
What is the likelihood of inheriting Huntington’s if one parent is affected?
Huntington’s is auto-dom, so 50% (regardless of gender).
Explain anticipation in Huntington’s.
Early onset is a/w greater # of CAG repeats.
During spermatogenesis, the CAG repeats in the abnormal gene rapidly increase. So, pts who get it from their fathers will have more CAG repeats and will get it earlier.
If they get it from the mom, will get it at the same age, bc the # of CAG repeats stays the same in maternal txmsn.
So, there expansion of CAG repeats in paternal txmsn, and anticipation in those who get it from their fathers.
What are the changes in the brain anatomy in Huntington’s?
Atrophy of the caudate nucleus- causing loss of GABA (hence the chorea)
Enlarged lateral ventricles (bc caudate degeneration), atrophy of putamen, defined sulci.
How is GABA made?
Glutamate –> GABA, but must have Vit B6!
In Vit B6 deficiency will not have GABA.
Chorea
sudden jerky purposeless mvmts
characteristic for basal ganglia lesion (Huntington’s)
Athetosis
Slow, writhing mvmts
Esp of fingers
Characteristic of basal ganglia lesion (huntington’s)
Myoclonus
Sudden, brief muscle contraction
Jerks, hiccups (aka singultus)
Dystonia
Sustained, involuntary muscle contraction
Writer’s cramp, torticolis
What is the treatment for Huntington’s?
Dopamine antagonist- Haloperidol
What diseases commonly feature anticipation?
Trinucleotide repeats: Huntington's Fragile X Myotonic dystrophy Friedreich's ataxia
What kind of tremor is a/w cerebellar dysfunction?
Intention tremor- slow zig-zagging when pointing toward a target. Can’t mv limb in straight trajectory.
Resting tremor
most noticeable distally
seen in Parkinson’s (pill-rolling tremor)
disappears w mvmt
What is the treatment for an essential/postural tremor?
Beta blockers
Pts often self-medicate w alcohol, which decreases the tremor
What are the genetics of essential tremor?
Autosomal dominant.
50% of pts who have essential have a fam hx
What kind of tremor gets worse with action?
Essential/postural tremor (worsens when holding posture)
What does the central sulcus separate?
The frontal lobe (in front of the sulcus) from the parietal lobe (posterior to the sulcus)
Where is the principal motor area located?
The precentral gyrus (the part of the frontal lobe that is directly anterior to the sulcus)
Just like in a car- the motor is in the front!
Where is Wernecke’s area located?
In the temporal lobe, in the dominant hemisphere (usu left)
aka associative auditory cortex
Where is the principle visual cortex located?
Occipital lobe
Where is the Sylvian fissue?
Between the temporal lobe and frontal lobe
Aka lateral sulcus
Where is the primary auditory cortex?
Inside/underneath the lateral sulcus
Aka Herschl’s gyrus, transverse temporal gyrus
Where is the primary sensory area located?
The post-central gyrus, part of the parietal lobe.
Just posterior to the central sulcus.
Where are the frontal eye fields located?
Frontal lobe.
Where is Broca’s area?
In the frontal lobe, dominant hemisphere (usu left)
This does motor speech.
What is the connection between Broca’s and Wernicke’s areas? What happens if it is lesioned?
Arcuate fasciculus
Lesioned = can’t repeat sentences
What does the frontal lobe do?
Executive fns- planning, inhibition, concentration, orientation, language, abstraction, judgement, motor regulation, mood.
Frontal lobe lesion - lack of social judgement. (Damage = Disinhibition)
Homunculus
Used to localize lesion (e.g what blood vessel is occluded) by looking at deficits
There is a motor homunculus (precentral gyrus) and a sensory homunculus (postcentral gyrus)
Legs/trunk are medial
Hands in the middle
Face lateral
ACA is medial
MCA is lateral
If there is a motor problem with the leg, what artery is occluded/dmgd?
The ACA on the contralateral side.
B/c ACA supplies medial, area, and legs are medial on the motor homunculus.
What arteries give the ACA, MCA, and PCA?
Internal Carotid gives the ACA and MCA
Basilar gives the PCA
They all anastomose at the circle of willis
What area of the brain does the ACA supply?
Anteriomedial surface
Anterior (front) and medial (inside)
Basically a strip down the middle.
What area of the brain does the MCA supply?
Lateral surface
the sides
What area of the brain does the PCA supply?
Posterior and inferior surfaces
the back and the bottom (also medially the back and bottom)
Bilateral amygdala lesion
Kluver-Bucy syndrome
Hyperorality, hypersexuality, disinhibited behavior
A/w HSV-1
Frontal lobe lesion
Disinhibition and deficits in concentration, orientation, judgement
May have reemergence of primary reflexes
Right parietal lobe lesion (assuming this is the non-dominant side)
Spatial neglect syndrome (aka hemi spatial neglect)- agnosia of the contralateral(!) side of the world.
So not acknowledging L side eg only put makeup on one side of face
Left parietal lobe lesion (assuming left is dominant)
Gerstmann Syndrome:
Agraphia (can’t write)
Acalculia (can’t calculate/do math)
Finger agnosia- can’t distinguish fingers
L-R disorientation- can’t tell left from right
Lesion of Reticular Activating System
Reduced arousal and reduced wakefulness, coma
Bilateral mammillary body lesion
Wernicke-Korsakoff syndrome Wernecke: Confusion + Opthalmoplegia + Ataxia Korsakoff: Memory loss, confabulation, personality chg
Common in alcoholics
Lesion to basal ganglia
Depends on what part- can have resting tremor, chorea, athetosis
Lesion to Cerebellar Hemisphere
Intention tremor, limb ataxia (cerebellar hemispheres are laterally located- affect the lateral limbs)
Dmg to the cerebellum results in ipsilateral deficits bc the pathways cross twice: cerebellum –> SCP (cross)–> contralateral cortex –> corticospinal decussation (cross) –> Ipsilateral.
If there is lesion to a cerebellar hemisphere, would you fall toward or away from the side of the lesion?
Toward the lesion.
Cerebellar lesions are ipsilateral (bc they cross twice).
Eg leg would be messed up if there was a lesion on the same side.
Lesion to cerebellar vermis
Truncal ataxia, dysarthria
Vermis is centrally located- affects central body.
Lesion to Subthalamic Nucleus (STN)
Contralateral hemiballismus
Lesion to the hippocampus
Anterograde amnesia- can’t make new memories
Lesion to the paramedian pontine reticular formation (PPRF)
Eyes look AWAY from the side of the lesion.
Lesion to the frontal eye fields (in the frontal lobe)
Eyes look TOWARD the lesion
Lesion to the superior colliculi
Paralysis of upward gaze
aka Paranaud’s syndrome
What is central pontine myelinolysis?
Acute paralysis, dysarthria, dysphagia, diplopia, and loss of consciousness.
Commonly caused by v rapid correction of hyponatremia- the osmotic shift damages the pontine neurons.
MRI will show increased signal in the pons
Once this occurs it is irreversible! Be careful!
Injury to the recurrent laryngeal nerve
Lose all laryngeal muscles except for cricothyroid.
Causes hoarseness
Often injured in thyroidectomy.
What artery supplies Broca’s and Wernicke’s areas?
MCA
Superior division of MCA –> Broca’s
Inferior division of MCA –> Wernicke’s
What’s the difference b/t aphasia and dysarthria?
Aphasia - higher-order inability to speak
Dysarthria - mechanical motor inability to speak (problem w tongue, mouth)
What is Broca’s aphasia?
Broca’s broken boca
Non-fluent aphasia (can’t speak) but can comprehend just fine.
Broca’s area is in the inferior frontal gyrus, supplied by superior division of MCA.
What is Wernicke’s aphasia?
Wernicke’s is wordy, but makes no sense.
Fluent aphasia (can speak) but impaired comprehension.
Wernicke’s area is in the superior temporal gyrus, supplied by inferior division of MCA
Global aphasia
Broca’s + Wernicke’s
Nonfluent + no comprehension.
Both areas are affected d/t lg MCA infarct which dmgs both superior and inferior divisions.
Conduction aphasia
Problem w arcuate fasciculus, which connects Broca’s and Wernicke’s areas.
Fluent speech and intact comprehension, but poor repetition- can’t repeat a sentence.
Non-dominant Broca’s aphasia
Expressive dysprosody- inability to express emotion or inflection in speech.
Non-dominant Wernicke’s aphasia
Receptive dysprosody- inability to comprehend emotion or inflection in speech.
Where are the “watershed zones” of the brain?
Areas most susceptible to hypoperfusion-
B/t the ACA and MCA
B/t the MCA and PCA
What happens if the ACA/MCA watershed zone is infarcted?
THis mediates the proximal arm/leg (motor homunculus), so a lesion –> “man in barrel”
Pts can walk, but arms dangle and hips are weak.
What happens if the MCA/PCA watershed zone is infarcted?
This mediates the occipital lobe, so lesion causes visual agnosia (brain can’t recognize objects, even tho pt can see them) and cortical blindness.
Top 4 most common brain tumors in adults
MGM Studios:
- Metastasis
- Glioblastoma multiforme
- Meningioma
- Schwannoma
50% of adult brain tumors are metastases.
2,3,4 are primary brain tumors; primary tumors rarely undergo metatstasis.
Sx of a brain tumor
Clincal px is usu d/t mass effects- new onset seizures, dementia, focal neurological lesions, headache
Dx by MRI or CT
Where are brain tumors usually located in adults vs in children?
In adults- usu supratentorial (in cerebral cortex)
In kids- usu infratentoral (in cerebellum, or in brainstem)
Where do metastases in adults usually present?
at the gray-white jn
usu well-circumscribed
Glioblastoma multiforme
most common primary brain tumor, also the worst pgx: pleomorphic tumor cells which border central areas of necrosis and hemorrhage.
What kind of stain is used for glioblastoma multiforme?
GFAP- this is the stain for astrocytes
glioblastoma multiforme is a type of astrocytoma.
Meningioma
2nd most common primary brain tumor
Most often occurs at convexities of hemispheres and the parasagital region. Esp the falx.
Arises from arachnoid cells external to the brain. Resectable.
See spindle cells concentrically arranged in a whorled pattern; psamomma bodies (laminated calcifications)
Schwannoma
3rd most common primary brain tumor. Schwann cell origin Often localized to CN VIII: acoustic schwannoma Usu found at cerebellopontine angle Resectable S-100 positive (bc S-100 is in cells that are from neural crest, and schwann cells are) Unilateral --> vertigo Bilateral- found in NF 2
Oligodendroglioma
Rare, slow-growing
Most often in frontal lobes
Chickenwre capillary pattern; oligodendrocytes have a fried egg appearance- round nuclei w clear cytoplasm; they are often calcified in oligodendroglioma
What do oligodendrogliomas cause if they are in the frontal lobe? If they are in the temporal lobe?
Frontal- focal hemiparesis
Temporal- seizure
What does the embryologic Rathke’s pouch give rise to?
Anterior pituitary
Pituitary adenoma
Most commonly a prolactinoma.
Bitemporal hemianopia (d/t prs on optic chiasm) and either hyper- or hypo-pituitarism are sequelae.
Originates from Rathke’s pouch.
While it can have mass effects on optic chiasm, usu noticed for its endocrine sx first.
What sx might be seen with prolactinoma?
Amenorrhea
Hypogonadism
Galactorrhea
Astrocytoma aka pilocytic (low-grade) astrocytoma
Most common primary brain tumor in kids Usu well circumscribed Most often found in posterior fossa May be supratentorial GFAP positive; S-100 tumor marker Benign, good pgx See Rosenthal fibers- eosinophilic, corkscrew fibers (swollen pink axons) Cystic and solid grossly.
Medulloblastoma
2nd most common primary brain tumor in kids
Highly malignant
Cerebellar
A form of PNET- primitive neuroectodermal tumor (small blue-cell tumor)
Can compress 4th ventricle, causing hydrocephalus.
A/w APC gene mutation (and Turncott syndrome)
See Homer-Wright rosettes.
Solid (gross), blue cells on histo.
Radiosensitive.
What is the difference b/t Homer-Wright rosettes and perivascular rosettes?
Homer-Wright = tumor cells around a fibril Perivascular = tumor cells around a vessel
Ependymoma
3rd most common childhood primary brain tumor
Commonly found in 4th ventricle, so can cause hydrocephalus
Slow growing, but poor pgx.
Perivascular pseudorosettes.
Rod-shaped blepharoplasts (basal ciliary bodies) found near the nucleus.
Hemangioblastoma
Childhood brain tumor, most often cerebellar
A/w VHL syndrome when found w retinal angiomas
Can produce EPO –> secondary polycythemia
Foamy cells and high vascularity are characteristic; Lipid inclusions stain red.
What are the tumors a/w VHL?
Retinal angioma Renal cell carcinoma Pheochromocytoma Pancreatic cysts neuroendocrine tumors Hemangioblastoma
Craniopharyngioma
Benign childhood brain tumor
Often confused w pituitary adenoma bc it can also cause bitemporal hemianopia, and it is also derived from Rathke’s pouch.
Most common supratentorial tumor in kids
Calcification and cysts are common- like tooth enamel.
Pit adenoma = hypersecretion of 1 hormone, while craniopharyngioma = hyposecretion and a mixed hormonal picture.
What childhood brain tumors can cause hydrocephalus?
Medulloblastoma (compresses 4th ventricle)
Ependymoma (inside of 4th ventricle)
Tumor cause of bitemporal hemianopia in adults vs kids
Adults- pituitary adenoma
Kids- craniopharyngioma
What are the main anti-neoplastic drugs used to treat brain tumors?
Nitrosureas (end in “stine”- eg -mustine)
What are the tumors a/w VHL?
Retinal angioma Renal cell carcinoma Pheochromocytoma Pancreatic cysts neuroendocrine tumors Hemangioblastoma
Craniopharyngioma
Benign childhood brain tumor
Often confused w pituitary adenoma bc it can also cause bitemporal hemianopia, and it is also derived from Rathke’s pouch.
Most common supratentorial tumor in kids
Calcification and cysts are common- like tooth enamel.
Pit adenoma = hypersecretion of 1 hormone, while craniopharyngioma = hyposecretion and a mixed hormonal picture.
What childhood brain tumors can cause hydrocephalus?
Medulloblastoma (compresses 4th ventricle)
Ependymoma (inside of 4th ventricle)
Tumor cause of bitemporal hemianopia in adults vs kids
Adults- pituitary adenoma
Kids- craniopharyngioma
What are the main anti-neoplastic drugs used to treat brain tumors?
Nitrosureas (end in “stine”- eg -mustine)
3 most common brain tumors in kids
- Pilocytic astrocytoma
- Medulloblastoma
- Ependymoma
Brain tumor w pseudopallisading necrosis
Glioblastoma multiforme
Brain tumor causing polycythemia
Hemangioblastoma
bc it makes EPO
Brain tumor involved in NF2
Schwannoma
Brain tumor a/w VHL syndrome
Hemangioblastoma
Brain tumor w foamy cells and high vascularity
Hemangioblastoma
Brain tumor causing prolactinemia (anovulation, amenorrhea, galactorrhea)
Pitutary adenoma
Brain tumor w psamomma bodies
Meningioma
Brain tumor w fried egg appearance
Oligodendroglioma
Brain tumor w perivascular pseudorosettes
Ependymoma
Brain tumor w Homer-Wright rosettes
Medulloblastoma
Brain tumor w the worst pgx
Glioblastoma multiforme
