NEUROSCIENCE

the longitudinal fissure does not form properly and causes defects like the cyclopia --most often associated with SHH abnormalities because it is present in the midline 

People with Patau syndrome and fetal alcohol syndrome are more likely to acquire this

congenital aqueductal stenosis 

--Chiari Malformations: cerebellum dislocates and pushes on the vertebral canal-- there is a canal associated there-- pushing against it causes back flow of the fluid also causing hydrocephalus

All of the ventricles are interconnected. Of them all cerebral aqueduct is the most narrow and occlusions can cause fluid to become backed up and cause hydrocephalus 

this can cause cerebral and white matter atrophy (neuron death)

• medulla (have an alar plate--4 medullary columns and basal plate--3 medullary columns)
• lower part of the fourth ventricle

• Pons (ventral basal plate)
• and the cerebellum (dorsal alar plate)
• upper part of the fourth ventricle

Remains the Midbrain-- alar plate (superior and inferior colliculi--vision and auditory respectively)

basal plate-- substantia niagra (reward and movement) and red nucleus (motor coordination) 

Associated with the aueduct

All the thalamus containing structures 

Epithalamus becomes the pineal gland and HABENULA (reward circuitary)

post pituitary 

associated with the third ventricle

derived from the forebrain (proencephalon): cerebral hemispheres and the lateral ventricles

At the cranial end of the neural tube initially 3 vesicles are formed: forebrain, midbrain, and the hindbrain 

After a couple weeks the forebrain (prosencephalon) separates into the telencephalon and the dicencephalon 

Midbrain remains--aka mesencephalon 

Hindbrain (rhombencephalon)-- Mete and Myel 


"Tel Di MES met My"

separates the alar and basal plate 

important for function--The segregation facilitates the formation of specific neural circuits and pathways within the central nervous system.

Consist of neuroblasts and glioblasts 

Alar plate--at the top and responds to BMP which is released by the dorsal layer (ectoderm)-- information arrives here so this will be the sensory neurons

Basilar plate-- at the bottom and responds to SHH which is released by the notochord ).. so this is more ventral--information will leave here so motor neurons

This applies for both the brain and the spinal cord. 

Neural Tube--medial (near the cavity--CSF) you have the neuroepithelial cells (neural ectodermal): VENTRICULAR 

These cells proliferate and differentiate in the mantle zone (intermediate zone) and this is where the gray bodies are located

Axons extend and create the marginal zone--white matter

Most development occurs during weeks 3-8 so exposure to any sort of teratogen will be most impactful during this time

• You can do an ultrasound at 20 weeks and onwards 
• You can do blood tests on the mother to test for AchE (which is usually not significant in the blood--but if baby has a defect elevated amounts of this is found in the blood) 
• You can also do a blood test to detect a-fetoprotein 

To confirm you can do amniocentesis and check the fluid of the fetus for fetal alpha protein

• Nutritional deficiencies-- folate 
• genetic
• environmental toxins--valproic acid, methotrextate, retinoic acid, maternal DM, TORCHes (infections that can cross the maternal fetal barrier), Phenytoin

• The entire spinal cord and the cauda equina are protected by meninges. 
• Terminale refers to the pia matter attaching to the the coccyx allowing for structural support. This support helps prevent excessive movement or displacement of the spinal cord and spinal nerves during activities such as bending, stretching, or other mechanical stresses.

bundle of nerves that extend inferiorly from the medullary cone of the spinal cord

it includes all 5 sacryl nerves, 1 coccyl nerve, and all the lumbar nerves from L1 or L2 depending on where the cone ends

initially the vertebra and the medullary cone are at the same height. 

The vertebrae outgrows the medullary cone and ends at around L1-L2... that is why the lumbar puncture is done at L3 so that you are not damaging the cone which consists the cell bodies 

There are nerves from the medullary cone that extend downwards 

MEDULLARY CONE not the same as MEDULLA.

• Called the meninges: comprised of the
• dura mater (outermost layer)-mesoderm derived 
• arachnoid-- middle--neural crest cells
• pia (inner)--neural crest cells

• usual sympathetic pathway: preganglion.. postganglion.. and target cell
• but for adrenal medulla the postganglion cell is in the target adrenal medulla cell and it releases NE/Epi... it doesn't have an axon

• B1: cardiac; increases force and rate of contraction 
• b2: lungs: dilation
•       VASCULAR: DECREASES VASOCONSTRICTION (INCREASES BLOOD FLOW)

Alpha 1: vascular smooth muscle-- constriction--increases blood pressure 

Alpha 2: presynaptic terminal: decreases NT release. also increases vasoconstriction

There are two subclasses of receptors alpha and beta--within alpha there are 2 classes and within beta there are 3 classes--they are associated with different downstream signaling molecules and have either excitatory or inhibitory responses

they are essentially the same molecules and are released during sympathetic activation by adrenal medulla predominantly and other postganglions of the sympathetic pathway 

difference: epinephrine has effects on more organs than NE does

Tyrosine--->dopamine--->epinephrine (norepinephrine). Stored in a vesicle. Released with calcium uptake 

Clearance: diffuses into the blood stream and thus can cause widspread effects.

Can bind to NE transporter on the presynaptic cell and either be reused or broken down

IT Can also bind to receptors on the presynaptic cleft and decrease the release of neurotransmitters--modulates its activity

celiac ganglion: stomach, spleen, liver, and gallbladder 

superior mesenteric ganglion: small intestine and ascending and transverse colon

inferior mesenteric ganglion: descending colon, kidney, bladder.

How much the post synaptic potential is in comparison to the threshold required to produce an action potential. 

Neurons less than 1: The graded potential is less than the threshold required to trigger an action potential. (neurons)

Greater than 1: muscular-- the graded potential (EPP) is greater than the threshold required to trigger and action potential.. because the amount of AchR are greater due to the junctional folds--greater surface area and the amount of neurotransmitter released is a lot more than required.

voltage gated sodium channels, amount of NT released, amount of NT receptor dictate the safety factors.

Vesicle has a protein called Synaptobrevin which binds to plasma membrane, syntaxin and SNAP. 

Calcium bings to synaptotagmin and initiates release 


":breve (brave) to inch forward.. calcium "tags" to go"

An empty vesicle is brought to the terminal and the material needed to make the NT is also sent to the axon terminal-- the NT is made at the end and then loaded into the vesicle:

Primary active transport: ATP is used to transport H ions against the gradient into the vesicle.

Secondary active transport: H is taken out of the vesicle with the gradient and then the NT is brought into the vesicle against the gradient

• vagus nerve
• Dorsal motor nucleus in the medulla (basal plate) which has a post ganglion in several locations (most often on the target organs) innervates the abdomen and the thoracic cavity

inferior salivary nucleus in the medulla innervates the otic ganglion which goes and innervates the paratoid gland 

all these glands make saliva but contribute different amounts

Pons house the superior salivatory nucleus which goes and synapses with the pterygopalatine ganglion which innervates the lacrimal and the nasal glands 

via the submandibular ganglion it innervates the submandibular and sublingual gland

Starts in the midbrain with the EDINGER nucleus and then synapses at the ciliary ganglion which then goes and innervates the sphinter pupillae and the ciliary muscle

• 3: ciliary muscle and pupil constrictor (occulomotor nerve)
• 7: All other glands (facial nerve)
• 9: parotid gland (glossopharyngeal nerve)
• 10: abdomen and thoracic (vagus nerve)

The only nerves from this that affect the Parasym/sym unit are the sacral nerves-- these affect CU PKU (Colon, urinary tract (bladder), penis, kidney, uterus

Most organs are innervated by both the parasympathetic and sympathetic nervous system-- so if you lose one the other one gets activated essentially

EXCEPT PILORECTOR MUSCLES, sweat glands, AND BLOOD VESSELS of the skin and extremities (only have sympathetic input)... these regions depending on the amount of NT released will either cause dilation or contraction--no dual innervation required

• located on vascular endothelial and many other surfaces 
• Ach induces NO release which stimulates the effector function

• Trimethaphan--Aortic dissection 
• the effect will be on whatever innervation is more dominant 
• because of dual innervation and difficulty predicting whether sympathetic or parasympathetic will prevail-- this drug is often not used

• Neostigmine 
• Physostigmine 

"stick with me : stig with me" stay in the synaptic cleft

reactivates the acetylcholinesterase enzyme--given during organophosphate poisoning--reverses irreversible modifications (add a phosphate group to the active site of the enzyme)

inhalation for COPD treatment 

a tertiary amine-- it is a muscarinic antagonist

a tertiary amine-- it is a muscarinic antagonist 

reduce motion sickness and reduce secretions

• alpha 2 agonists that decrease the NE release in periphery 
• and decrease sympathetic outflow in the brain

dry mouth because glands are not secreting fluids appropriately

a tertiary amine-- it is a muscarinic antagonist 

• USES: mydriasis eye exam (dilation can cause blurry eye)
• bradycardia
• organophosphate poisoning 
• mushroom ingestion

they irreversibly inactivate acetylcholinesterase so can induce significant parasympathetic effects which is depression of function

• pentamers 
• made up of diverse subunits 
• alpha subunit greater in sym than in para

AchE inhibitors and muscarininc agonists because they mimic acetylcholine function

adverse effects are predominantly due to over-activation of parasympathetic system..can also have an effect on nicotinic receptors 

CONTRAINDICATIONS: peptide ulcer, obstructions, COPD, asthma

muscarinic agonist

muscarinic agonist

"acetylcholine agonist"-- Ach typically gets hydrolyzed too fast so it cannot be clinically used and its not specific to muscurinic or nicotinic receptors-- but you can add amino groups to Ach and this prevents hydrolysis..

quaternary structure-- permanently charged ammonium compound so it cannot cross the blood brain barrier-- orally it can't be absorbed well either however it can still have some affect on the GI tract 

Lipid soluble tertiary amines can get through the barriers

paralyzes mucles by inhibiting snap and preventing the release of ACH into the cleft

they are found on the target cells of the parasympathetic pathway:

glaucoma: topicla application that will enhance drainage of aqueous humor 

gastroparesis, urinary retention, diminished bowel motility: agonists cause smooth muscle contraction

• Nonselective: 
• Tolazoline Dibenamine Phenytolu(reversible) Phenyoxyben(irreversible)

Most common clinical use is in neuro tumors that release a lot of epinephrine 

• Selective alpha1 antagonist: Doxazosin Terazosin Prazosin 
• vasoconstriction which causes increase in peripheral resistance and thus BP-- there may be a reflexive decrease in heart rate

• Caused by excessive blood flow to the nose 
• --there are a lot of a1 receptors here so you can give an agonist and this will cause constriction and limit the congestion 

--parasympathetic: overactive can increase secretions and cause congestion-- can give muscarinic antagonist

approved for nasal decongestion

-increases the amount of NE that is released into the cleft either by inhibiting the reuptake proteins or by inducing calcium independent release of NE

Sympathomimetics--elevate the concentration of catcholamines by calcium independent release: amphetamine is able to be uptaken via NET and then stimulate the release of transmitter

reuptake inhibitors (cocaine)

readily cross bbb

not really agonists

• SE: stimulant, increased HR,
• Used for ADHD

• Reuptake molecules is primary 
• COMT (in other cells) and MOA in neurons is secondary to eliminate the remaining

linked to G receptors that then go and activate ion gated channels and depending on which they activate it will cause depolarization in the D1 type and either d or h polarization in D2 type

Dopamine is mainly involved in the brain-- substansia nigra (motor--parkinson's, mesolimbic (reward-- schizophrenia), tuberoinfundibular 

also has a role in the sympathetic nervous system--in the renal pathway

selective b2 receptor agonist

• asthma management 
• suppresses preterm uterine contractions 

• SE: 
• tachycardia, tolerance development, and skeletal muscle tremors.

selective b1 agonist--works on the heart which causes increased heart rate and force of contraction--- NO NET CHANGE IN peripheral vascular resistance 

heart failure, cardiogenic shock are the clinical applications

• AGONIST nonselective B receptor stimulator--activates all B subtypes 
• vasodilation, lowers blood pressure

selective a2 receptor 

clonidine and guanfacine: lipid soluble--cross the blood brain barrier- causes a reduction in the sympathetic outflow (effect in the brain).

peripherally: curtail the release of norepinephrine so cause a decrease in BP, peripheral resistance, heart rate, and cardiac output

selective alpha 1 agonists--predominantly causes vasoconstriction and increases the total peripheral resistance--decrease in heart rate--reflexive change to the elevated BP--similar to NE effect on A1 but more prolonged effect

• Acts on alpha 1, 2 and beta 1---but not b2
• increase the peripheral resistance and causes an increase in the blood pressure-- this causes a reflexive decrease in heart rate

• give in septic shock--where you want to increase the blood pressure and decrease the heart rate
• because it doesn't work on B2 not indicated for anaphylactic shock

organophosphate

Atrophine and pralidoxime

an example of a organophosphate--irreversible inhibition of AchE

The enzyme that breaks down Ach is inhibited so Ach remains in the system longer 

• Diaphoresis/defecation 
• Urine 
• Miosis 
• Bronchospasm 
• Emesis
• Lacrimation (tears)
• S--saliva

They are innervated by the sympathetic system--but instead of the nerve releasing epinephrine it releases Ach which binds to muscarinic receptors on the sweat gland

competitive antagonist of the nicotinic receptor on the muscles specifically 

it is similar to d-tubocurarine 

non-depolarizing block

Competitive antagonists-- d-tubocurarine binds and prevents the channel from opening so there is no muscle contraction 

Depolarizing neuromuscular blockers: Succinylcholine: binds to the receptor and blocks the gate so that it remains open and causes and influx of ions--depolarized-- and won't be degraded by AchE eventually can cause desensitization to Ach and paralysis

This has to do with the peripheral nerves innervating the skin being overly responsive to NE-- causing increased vasoconstriction

Hypothalamus innervates the preganglion in the spinal cord which then forms a synapse with the postganglion in the spinal cord which innervates the smooth muscle of the eyelid, dilator pupillae, sweat glands, and blood vessels. 

There can be a lesion at any of these points and it causes decrease in the sympathetic response: ptosis, myosis, skin flushing

Denervation hypersensitivity-- if NE comes nearby from the blood the receptors will become hyperactive and cause the opposite of all the responses noted above

• to prevent another stroke 
• aspirin 
• clopidegrel
• both together are hardly recommended because it can increase the risk of bleeding 

Anticoagulants are indicated if coagulation issue OR AFIB

• --EKG (aflutter)
• --MRI
• --labs (DM, hyperlipidemia)
• --ECHOCARDIOGRAM (heart function)

• --brain injury/ neurosurgery (can cause bleeding) within the past 3 months 
• --stroke in the past 3 months
• --endocarditis

• Thrombolytics-- tpA/"plase" that activates plasmin which goes and breaks down active clots 
•     tpa benefit: requires reduced treatment time: has to be given within 5 hours and have to have deficits present--otherwise the longer the time has been the more deficit you have and the benefits do not outweigh the risks

Endovascular therapy-- you insert a catheter through the femoral or radial artery and remove the clot 

in both cases the blood pressure should be kept below 180 to prevent bleeding but also after the treatment to prevent reperfusion injury

determines the likelihood of developing a stroke after having TIA

Blockage from a clot that can self resolve and it leaves behind no evident signs of damage on imaging 

but these people have greater chance of having a stroke in the future and so should be managed and treated the same way as people who are having a stroke

it won't show you an infraction early on--these become more evident later on (both MRI and CT can detect old strokes as well)

but you order to see if there is a mass or bleeding

• Blood sugar check (to r/o glycemic cause) 
• NON-CONTRAST CT brain 
• CT angiogram 

NIH score-- the greater the stroke the more severe it is and the more likely it is related to a large artery

when you have prior brain injury, neurons in other areas can do double duty-- but when there is another stress in the body like infection.. the body has to redirect its nutrients and there will not be enough nutrients to fuel the double duty neurons so this can mimic a stroke

• migraines with an aura (the aura sx can mimic strokes)
• hyper/hypoglycemia 
• seizure 
• recrudescence

• 1. Fatty deposits accumulate in the arteries and can rupture causing clotting 
• 2. hypoperfusion (due to narrowing by atherosclerotic plaques or by septic shock)
• 3. Plaque can directly block a capillary and prevent the blood flow

Carotid and vertebral arteries are main and they connect with MCA PCA AND ACA

projections of the pia matter that attach to the dura mater- the dura mater attaches to the vertebral column-- this allows lateral fixation of the spinal cord--

• buldging that compresses the nerve
• in cervical: the nerve above the disc is affected regardless of where the budge occurs (if it occurs closer to the cord or further away)

in lumbar if the herniation occurs closer to the spinal cord it will affect the nerve going below and if it occurs further away it will affect the nerve above

there are 8 cervical nerves but 7 vertebrae-- the cranial nerves exit above the corresponding vertebrae in the cervical region and then from thoracic downwards they leave below corresponding foramen.

Aorta splits into two vertebral arteries each vertebral artery splits in many anterior and posterior radicular arteries.. the anterior arteries from both sides come together at ADAM vessel and merge to create the anterior spinal artery which supplies the anterior part of the spinal cord. The posterior arteries from both sides remain seperate and innervate the posterior side of the spinal cord

Facet joints located on the raised sides of the transverse process (superior facets) and on spinal process (inferior facets)

allow for: flexion (bend forward), extension (bend backward), and twisting motion

Neural Foramen aka interverbral foramen-- space in between the pedicle where the nerves are able to exit

intervetebral disc: is the substance inside the vertebral body (bone) and it extends a little beyond the bone too--made up of cartilage and gel like substance nucleolus polosum (notochord derived)

• Loss of grey white differentiation 
• Sulcal effacement-- one side may have prominent sulci than another 

• Loss of basal ganglia definition 

• hyperdense blood vessel 

Left atrial appendage-- its shape and location makes it more to stagnant blood flow due to conditions like Afib (most prevalent)

Small vessel disease-- involving subcortical structures (internal capsule, basal ganglia, thalamus, brainstem)--usually lacunar strokes and don't cause noticeable symptoms but can become problematic accumulatively --- due to vascular changes due to risk factors like DM, hyperlipidemia, HTN, smoking, alcohol 

• large vessel stenosis--Posterior cerebral (occipital) and anterior cerebral artery (lower limbs)
• middle cerebral artery (face and hands)

cardioembolism--due to afib/aflutter or systolic heart failure where the blood flow is impaired and there is pooling causing clots--most commonly starts in the left side of the heart

Angiogram that shows a blockage of the artery--ischemic stroke

dark spots-- infraction (ischemia)

bright spots-- bleeding

• -headache 
• -hiccups 
• -dizziness
• -trouble swallowing/voice change

Lacunar stroke--small penetrating branches of the cerebral arteries may become occluded, and the resulting infarcts may be so small or so situated as to cause no symptoms

tissue is removed by macrophages, a small cavity, or lacune, remains

• Pure sensory stroke--thalamus
• Pure motor hemiplegia--

MRI is more reliable than CT in demonstrating lacunes

they affect deeper structures because small blood vessels typically tend to penetrate the deeper structures and they are more affected by risk factors like DM, hypertension, hyperlipidemia

opening in the sacrum that allows you to access the spinal cord

the bone that is in between the facets

Crude touch=light touch itch or tickle...pressure of clothing against the skin, sensing the weight of an object in the hand, or perceiving someone's touch during a handshake.

fine touch-- texture and shape of an object (discriminatory touch)

very rare because you are required to knock out two of the posterior arteries

Usually penetrating trauma that damages one half of the spinal cord (hemisection) 

• "Brown-- Seq: segregated to one side
• penetration"

Neurological level-- the last normal spinal cord (you assess this by physical exam of dermatomes and myotomes)

(everything including that and above is normal)

• ASIA score:
• A: no motor or sensory function left (Complete --no sacral sparing)
• B: Sensory intact. No Muscle
• C-D: Muscle grade present to an extent 
• E: sensory and motor normal

black dots near the deeper structures of the brain indicate a hypertensive bleed

Chronic subarachnoid hemorrhages

• Black--indicates bleeds can be an ADW MRI 
• notice the small black dots in the outside of the cortex--chronic bleeds due to beta amyloid depositions affecting the integrity of the vasculature 
• CEREBRAL AMYLOID ANGIOPATHY

Basal ganglia/thalamus

subcortical are usually accompanied by deficits in arm, legs, and vision whereas cortical is not and most likely accompanied by things like aphasia, isolated weakness

Infarction--but on MRI brain bleeds and infarctions both appear white 

• on DWI MRI: both appear white (water resistance)
• on ADW: both appear black (amount of water molecules)
• (you would have had a CT to hone in on what it is)

Parasympathetic innervates the sphincter and constricts upon activation-- constricting the pupil 

Sympathetic innervates the radial muscle and has a1--it will constrict during activation but actually causes dilation of the eye

• E is only released by the adrenal medulla 
• at every other junction NE is released

increases MANY More alpha 1 because they are in majority-- so more constriction (a1) systolic increases.. causing MAP to increase... reflexive decrease in heart rate

Because of B1 heart rate will go up causing an increase in systolic 

DBP will do down (this affect is greater) so the MAP goes down... heart rate will increase in addition to affect on B1

Because NE affects a1 there will be an increase in SBP and thus MAP.. this will cause reflexive change in heart rate (decreased)

• a. SBP
• b. DBP

Low does epinephrine even though there isn't a change in map there is an increase in heart rate because of affect on B1 receptors

Pre-ganglionic cell releases Ach to nicotinic receptor on the post-ganglionic cell. Post ganglionic cell releases Ach to muscurinc receptors on the sweat glands

--- it binds to alpha 1 and causes vasoconstriction that causes increase in blood pressure this in turn causes Baroreceptors (located in the arteries) to stretch in response to the hypertension and they send signals to the medulla which then stimulates the vagus nerve to release Ach and decrease the heart rate

• alpha 1: most vessels
• beta 2: liver and skeletal 

the heart has b1 but the vasculature around there probably has b2 which does not

• Sympathetic: increases contractility, velocity, and heart rate (b1)
• para sympathetic--decreases velocity, and heart rate (M2)

Parasympathetic effect is greater in all organs except sweat, skin, vasculature , hair

because endothelial cells have muscarinic receptors and binding to these induces release of NO which then goes and causes vasodilation of the smooth muscles which in turn influences blood pressure

NE will have more pronounced effect on Alpha 1 because it is able to outcompete E.. than the other ones

• Begins in the eyes and can spread throughout the body 
• Crisis--- when respiratory muscles are affected (diaphragm also has a voluntary component.

MG is self antibodies that specifically targets Nm receptors. Blocks the Ach from binding but also will cause receptors to endocytose and become degraded. Will also cause complement proteins to start attacking the the muscular surface.

affects voluntary skeletal muscles--starts with the eyes first then the face then works its way downwards

• Grade A will have no improvement 
• Grade B can upgrade to C or D 
• Grade C IF UNDER 50 YOU CAN REGAIN FUNCTIONAL AMBULATION 
• Grade D can acquire functional ambulation 

• the level of functional ambulation that can be gained depends on the level of injury 
• C3-C5 ventilation dependent 
• C5: Power wheelchair 
• C6: Manual Wheelchair 
• C8: transfer in and out of the wheelchair 
• Thoracic level injury-- fully functional at the wheelchair level 
• L2: can walk short dx with brace 
• L3: can walk community level with brace

Complete injury will result in no sensory and motor function below the injury. Sacral sparing is when sensation and motor in S4 and S5 is spared

Yes the antibody effect can target the axon too and causing it to break

Neuromyelitis Optica

Neuromyelitis Optica

Neuromyelitis Optica

Neuromyelitis Optica

Neuromyelitis Optica --often around ventricles 

Neuromyelitis Optica

Neuromyelitis Optica

Neuromyelitis Optica

Neuromyelitis Optica

Neuromyelitis Optica

Neuromyelitis Optica

Neuromyelitis Optica

Atleast one core clinical characteristic if there is an antibody for the aquaporin or if not atleast 2 core clinical characteristic

MS affects the oligodendrocytes-- this disease affects astrocytes which are around dendrites and closer to the cell body--so the damage can cause cell body damage and necrosis (worse prognosis)

• Mimics MS
• -presents with: optic neuritis, myelitis, and POSTREMA SYNDROME (constant hiccups and nausea and vomiting that is not responding to medications for a long time) 

you can differentiate with MRI

While pregnant recurrence is low because immunosuppressed state--after delivery though relapses shot up

This is avoided if you stabilize them before they get pregnant-- once they get pregnant you may have to stop tx or consider other drugs that wont affect baby

• Determined based on safety, convenience, and efficacy. 
• Black males and if affected region is basal ganglia and cerebellum you may require more aggressive therapy

• MS: 
• Time (there has to be a time gap between two different neurological  symptoms) and Space gap (two different areas have to be affected)

Space gap can be proved by MRI and multiple lesions.. time is harder to prove in which case you have to do a lumbar puncture and find the antibodies (no specific one)

• There can be improvement and then relapse--during relapse condition stays the same. 
•  
• this can ultimately evolve into a secondary progressive condition where then you just get progressive worsening and accumulation of disease. 

primary progressive--symptoms are always there and it just gets worse 

progressive relapse--you keep getting relapses that keep getting worse with time

central vessel sign-- MS

MS

• MS sclerosis lesions-- they can go away as the relapse ends and then they can come back
• over time they can also join together and conglomerate

• -it is prominent in young females 
• -thumb tack lesions around the ventricles mainly and can be around the cortex too. 

• can present with any sort of neurological dysfunction 
• Most common:
• **Nystagmus/double vision with moving eyes all the way to the right or the left 
• **blurry vision and pain in one eye: optic neuritis

• -optic neuritis 
• -myelitis 
• -postrema-- hiccups and nausea and vomiting for a long duration with no relief from meds

• blocks all beta receptors and ALPHA 1 too 
• third generation beta clocker (antagonist)

• B1 blocker 
• minimizes resp side effects 

hypertension

first generation beta blocker (antagonist).. RESP SE

• USES: 
• -hypertension-- initially causes an elevation but eventually decreases b/c of renin 
• -angina/heart failure: reduces heart rate: making heart work less hard 
• -glaucoma: due to increased blood flow there is more fluid production by the sympathetic system-- so this reduced the blood blow by preventing vasodilation

If the immediate life threatening sxs are treated then in 3 months you can establish a new neuromuscular junction and regain SNARE proteins (botox wears off in 3 months)

anti-btx

also causes a loss of reflexes

autonomic involvement (which innervates the visceral organs) 

Nm involvement

3,4 Di-aminopyridine--blocks the potassium channel blocker to prolong the action potential to get more Ca2+ in

Detect the calcium antibody 

EMG--there shouldn't be improvement of function

Small cell lung cancer

Commonly starts at the legs and moves its way upwards 

improves with exercise 

depressed reflexes 

• Depressed weakness 
• And because it's an antibody that affects Ca2+ release, autonomic synapses and muscular synapses will be affected.

Cholinesterase Inhibitors (reversibles) 

Additionally you can give steroids (avoid in resp crisis patients) and other immunomodulants like Plasma exchange where you remove the antibodies

Chest XR and thyroid studies-- because MG is a paraneoplastic syndrome associated with thyoma-- should repeatedly monitor for cancer

You should also check pulmonary function throughout so you have a baseline of progression of disease

• used in tensilon test 
• can cause bradycardia (SO YOU CAN PRE TREAT WITH ATROPINE)

Ice pack test-- decreases the f(x) of AchE.. so there will be more Ach in the cleft to outcompete the antibodies 

Tensilon test-- AchE inhibitor-- short and fast 

Antibody test-- there are multiple antibodies so greater chance for false negatives 

Electromyography: stimulation and you should see a decline in function (fatigue)

skeletal muscles so it will only affect Nm receptors--autonomic system is not affected like it would be in Eaton Lambert's and Botulin

It will get worse as the day progresses and you are using the muscles more frequently. 

It is different from multiple sclerosis because this often consists of facial symptoms and then progresses whereas MS can have variety of neurological symptoms

Arachnoid and pia 

• **thunderclap HA, photophobia 
• ** trauma and aneurysm rupture (aneurysm has to be located more in the middle region

dura and arachnoid 

• Infants--non-accidental injury 
• young adults: MVA
• elderly: falls (bridging cortical veins)

• between Skull and dura 
• traumatic injury because requires torn meningeal artery 

LENS shaped

MCA bleed

ACA bleed

PCA vision will be affected

FLAIR: white matter is dark and cortex is bright (along with DWI, this test is a good second in terms of providing clinical info)

EDEMA from stroke, inflammatory disease (MS), brain tumor

Insular ribbon--early sign of acute stroke

in radiology your right is actually the left

• Tells you irreversible from reversible 
• identify pernumbra which is tissue that can be salvaged

they can do a vertebroplasty where they insert cement at the site of vertebral fractures 

they can also do CT guided biopsies of the brain

Direct catheter cerebral angiography

CTA requires contrast so anybody who is allergic to contrast should have this done 

Young children should have this done if available because less radiation

Depending on symptoms it advises what the best imaging with or without contrast you should order to attain the maximal information

innervate many structures: superficial and deep visceral organs 

and can detect many different stimuli: pain temperature, itch, mechanical, chemical

normal pain response... different from neuropathic pain which is due to disease or injury-- burning, stabbing, electrical, pins and needles, funny bone

Axial mesoderm