Neurology and Pain Flashcards
Muscular Dystrophy
The muscular dystrophies are an ______ group of ______ _____ disorders resulting from defects in a number of ____ required for normal _____ function
- Some of the genes responsible for these conditions have been identified:
- X linked inheritances (2)
- Autosomal recessive inheritances (4)
- Autosomal dominant inheritances (5)
inherited group of progressive myopathic disorders resulting from defects in a number of genes required for normal muscle funciton
- X linked
- Duchenne and Becker
- Emery-Dreifuss (EMD gene)
- Autosomal recessive
- Limb-girdle (2A, 2B, 2C, etc)
- Congenital
- Emery-Dreifuss (LMNA gene)
- Distal dystrophies
- Autosomal dominant
- Facioscapulohumeral
- Limb-girdle (1A, 1B, 1C, etc)
- Myotonic dystrophy type 1 (DM1) and type 2 (DM2)
- Distal dystrophies
- Emery Dreifuss (LMNA gene)
Muscular Dystrophy
- Most common form =
- DMD is caused by a defective gene located on the __ chromosome that is responsible for the production of ______
- Dystrophin is located on the cytoplasmic face of the plasma _____ of muscle fibers, functions as a large, tightly associated glycoprotein ____
- Function of Dystrophin =
- In its absence, the glycoprotein complex is _____ by proteases. Loss of these membrane proteins may initiate the _____ of muscle ____, resulting in muscle ______
- Duchenne Muscular Dystrophy
- X chromosome, Dystrophin
- Inside of plasma membrane, glycoprotein complex
- Stabilization of sarcolemma of the glycoprotein complex, thereby sheilding it from degradation
- digested, degeneration of muscle fibers -> muscle weakness
Muscular Dystrophy Clinical Course
- Usually ____ at birth
- _____ muscles of __ and ____ are usually first affected
- ______ of the calf muscles eventually develops
- Signs of muscle weakness become evident by _-_ yo
- asymptomatic
- Postural, hip and shoulders (stereotypical postural abnormality)
- Pseudohypertrophy (bc not actually muscle, is being replaced by adipose tissue)
- 2-3 yo
Muscular Dystrophy Clinical Course
- Imbalances between (2) lead to abnormal ____ and development of _____/joint _____
- S____ is common
- _____ usually needed by 7-12 yo
- Smooth muscle of ____ and ____ is preserved
- Respiratory muscles =
- Heart =
- Mortality =
- agonist and antagonist muscle groups -> abnormal postures -> contractures/joint immobility
- Scoliosis
- Wheelchair
- bladder and bowel (continence and normal bowel function)
- Diaphragm is unaffected but often involved dt immobility and results in weak and ineffective cought, frequent respiratory infections, decreased respiratory reserve
- Cardiomyopathy
- Usually occurs in young adulthood as a result of respiratory or cardiac complications
Picture of Muscular Dystrophy
Changes in Posture
- Back =
- Belly =
- Calves/some muscle groups =
- Joints =
- Arching
- Sticks out dt weak belly muscles
- Pseudohypertrohy
- Contractures (common in hands - happens where stronger muscle group pulls joints in certain positions) -> need constant physical therapy to prevent
Frustrating for children bc they can still feel their bodies, just can’t move it, usually living beyond 30’s is not common
Traumatic Head Injury
(3)
Skull Fractures
Parenchymal Injuries (TBI)
Traumatic Vascular Injury
Parenchymal Injury (TBI)
All forms of TBI can involve both primary (first ____) and secondary (brain ____, release of _____ ions/transmitters)
- Focal brain injuries (2)
- Diffuse brain injury (___ ____ ___) (1)
first injury, brain swelling, release of intracellular ions/transmitters
- Contusions, Lacerations
- (Diffuse axonal injury) Concussion
Traumatic Vascular Injury
(1)-(4)
Hematomas
- Epidural
- Subdural
- Subarachnoid
- Intraparenchymal
TBI (Notes)
- Primary Injury =
-
Secondary Injury =
-
Problems of increased ICP
- (1): bc BP has to be greater than ICP to perfuse the brain
- (1): ultimate consequence of brain swelling
- Release of intracellular contents such as Ca, Na, K neurotransmitters effects =
-
Problems of increased ICP
- Treatments to prevent secondary injuries =
- blow to the head
- release of intracellular contents dt cell death (inflammation, swelling, increased ICP)
- Elevated BP
- Brain herniation, instant death -> only one place pressure can be released at base of brain (where connected to spinal cord) -> so if pressure is relieved by this hole
- Effects excitability of the brain -> more injury dt seizures
- Craniotomy (to release pressure), Cooling of the body
TBI (Notes)
2 groups of brain injuries
-
Focal brain injuries = spatially focused injury, effecting __ part of the brain
- Contusions =
- Lacerations =
- Manifestations completely dependent on ___ of brain that is affected. Ex) injury to motor center = loss of _____ motor function
- Diffuse brain injury = ____ brain is effected, a rapid ____ or ____ of brain that creates a _____ stress
- one part of brain effected
- non penetrating bruises
- penetrating lacerations
- location, contralateral loss
- entire brain is effected, rapid acceleration or deceleration creates shearing stress
Mechanism of Closed Head Injury
- Brain is a bowl of ____ with ____ spider webs running through it
- Diffuse brain injury also known as diffuse _____ injury bc can get shocked and lose function momentarily to even getting physically damaged -> information flow from one place to another is effected
- Common cause (1)
- Coup or Counter Coup =
- jello, axon spider webs
- axonal
- MVA
- 1 type of injury that occurs when car is going 50mph -> crash -> body is going 50-0mph (body stops but head continues to accelerate (coup) then deceleration of head going back (counter coup)
- when head goes forward brain actually goes back, and when head goes back, brain goes forward
- 1 type of injury that occurs when car is going 50mph -> crash -> body is going 50-0mph (body stops but head continues to accelerate (coup) then deceleration of head going back (counter coup)
What is this a picture of?
Frontal Lobe Contusion
Concussion
Diffuse Brain Injury (Diffuse Axonal Injury)
What grades are these concussions?
- Some disturbance in attention or memory but no loss of consciousness
- may involve brief loss of consciousness (less than 5 min)
- Classic Cerebral Concussion- an immediate loss of consciousness that lasts more than 5 min but less than 6 hrs - involves temp disruption of the Reticular Activating System (RAS)
- temporary axonal disturbances
- Grade I and II
- Grade III
- Grade IV
- Mild Concussion
Reticular Activating System
=
- RAS is usually receiving _____ amounts of sensory ___ which determines level of (1) -> when constant stimulation goes dark with a terrible concussion -> is why you lose consciousness, waking up represents RAS coming back ____
- >6h loss of consciousness = ____
- Why can’t you sleep?
Important area of brain stem that acts as a relay station (where info from body is conveyed into brain)
- tremendous, input, cortical arousal, online
- coma
- when person is asleep cannot monitor consciousness and may have delayed loss of consciousness
Hematoma
Hematoma =
Intracranial hemorrhage =
Bleeding in the brain as a result of traumatic injury to blood vessles, classified by location
Bleeding within intracerebral blood vessel
Epidural Hematoma
Happens between ____ and _____
Most common cause =
Between skull bone and dura mater
Laceration of middle meningeal artery (artery located on both sides, hugs parietal side and right under skull)
Ex) someone hits their head, may have an almost undetectable skull fracture that lacerates middle meningeal, natasha richardson skiing accident - loss of consciousness occurred later (rly bad sign) dt bleeding, increased icp, herniation
Subdural Hematoma
Bleeding where?
Common cause:
- (2) populations where bridging veins more vulnerable to rupture from accel and decel
Beneath dura mater
Damage to bridging veins that runs through the mater and drains blood from cerebral cortex into central sinus
- Elderly (esp with brain atrophy)
- Young Children (vens more delicate) - subdural hematoma diagnostic for death from shaking baby
Cerebrovascular Diseases
Cerebrovascular Accidents (CVA, strokes)
(4)
Thrombotic Stroke
Embolic Stroke
Hemorrhagic Stroke
Lacunar Stroke
Strokes that cause
Focal Cerebral Ischemia =
Global Cerebral Ischemia =
Thrombotic, Embolic, Lacunar (affects particular vessels and a particular area)
Hemorrhagic Stroke (causes reduced perfusion to entire brain dt bleeding)
CVA, Strokes
= group of disorders that can cause ____ or ____ ischemia in the brain
Usually a result of a pathological medical problem (__, __) not traumatic injury
- (1): type of thrombotic stroke that occurs in specific blood vessels and tend to be very different and occur in a particular area of brain (microinfarcts from ruptured plaques that look like little ____ (lacunar) that happen in ___ of the brainstem, often happen over a period of ___ (can go _____ until ____ and affects respiratory/cv function)- major risk factor ____
- (1): caused by CV disease, result from ruptured athersclerotic plaque
- (1): caused dt lodged embolus in an arterial branch (more commonly a clot - usually starts on left side of heart dt Afib, valve disease)
- (1): often occurs from ruptured aneurysm (cause and significant effect: HTN)
focal, global
HTN, PE
- Lacunar lakes, pons, time, undetected, accumulate, HTN
- Thrombotic
- Embolic
- Hemorrhagic
Sensory and Motor Cortex
Controls the _____ side, for example the
- Left hemisphere of the motor cortex _____ the ____ side of the body
- Left hemisphere of the sensory cortex ______ input from the body’s _____ side
Contralateral
- controls right side
- receives input from right side
Brain and Behavior: The Language Circuit
- Wernicke’s Area: processes _____ input for language- important for ______ speech
- Angular Gyrus: part of the ______ Lobe -____ auditory input from the primary auditory area and other senses from the s_____ cortex and v____ cortex and ____ into _____ area
- Broca’s Area: receives input from Wernicke’s and controls the _____ of intelligible speech - lies near the primary ____ are that controls ____ movements that form words - the connection between broca’s and wernicke’s area is _______ to facilitate the integration of speech formation, comprehension, and editing
- auditory, understanding
- temporal lobe, combines auditory, somatosensory and visual, feeds into wernicke’s
- production, motor, tongue, bidirectional
Four Key Features of a Stroke
(4)
- Sudden Onset
- Focal Involvement of the Central Nervous System
- Lack of Rapid Resolution
- Vascular Cause
4 Key Features of Stroke (cont)
- Sudden Onset - the sudden onset of symptoms is documented by the _____
- Focal involvement of the central nervous system-The site of central nervous system involvement is suggested by the nature of the _____ and signs, delineated more precisely by a ____ exam and confirmed by imaging studies (2)
- Lack of Rapid Resolution- The duration of neuro deficits is documented by the history. In the past the standard definition of stroke required that deficits persist for at least __ hours to distinguish stroke from a TIA. However, any such time point is ____, and TIA’s usually resolve within __ hrs.
- Vascular Cause - A vascular cause may be inferred from the ____ onset of symptoms and often from the pt’s ___, the presence of ___ ____ for stroke, and the occurence of s/s referable to the territory of particular cerebral blood vessel. When confirmed by imaging, further investigations can be undertaken to identify a more specific etiology such as arterial ____, cardiogenic, _____, or _____ disorder.
- history
- symptoms, neuro, CT/MRI
- 24, arbitrary, 1 hr TIA
- acute, age, risk factors, thrombosis, embolus, clotting
- Site involved well predicted by nature of symptoms: motor symptoms (motor cortex), speech disturbances (broca or wernickes)etc*
- TIA vs. Stroke: TIA is transient (like the unstable angina of an MI)*
Types of Strokes
Acute Onset: strokes begin _____. Neuro deficits may be maximal at onset, as is common in _____ stroke, or may progress over seconds to hours (or occasionally days), which may occur with progressive arterial _____ or recurrent _____
(3)
abruptly, embolic, thrombosis, emboli
Transient Ischemic Attack (TIA)
Stroke in Evolution
Completed Stroke
Types of Strokes Definitions
- Progressing stroke, causes deficits that continue to worsen even as the patient is seen
- Defined by the presence of persistent deficits, which may be stable or improving when the patient is seen; does not necessarily imply that the entire territory of involved vessel is affected or that no improvement has occurred since the onset
- Produces neuro deficits that resolve completely within a short period, usually within 1 hr
- Stroke in Evolution
- Completed Stroke
- Transient Ischemic Attack (TIA)
Common Area where Strokes Occur
(1)
Classified by parts of brain they perfuse: _____ vs. ____ symptoms
Circle of Willis at base of brain
Anterior vs. Posterior Symptoms
Anterior vs. Posterior Strokes
Anterior =
Posterior =
HA, aphasia, visual field deficits, hemi or monoparesis (unilateral changes in movement/senssation)
More loss of consciousness, more visual field defects, less moement/sensory defects
Meninges Anatomy
What surrounds ventricles?
Layers of the meninges? (3)
Ependymal Cells
Dura, Arachnoid, Pia Mater
Ventricles of the Brain
Occupied by?
CSF (occupies ventricles and central canal of spinal cord)
Left and Right Ventricle
3rd Ventricle
4th Ventricle
- Choroid Plexus produces CSF
Composition of CSF (extracellular) vs. Plasma (intracellular)
Differences in composition (4)
Purpose:
- Na (less): reduce concentration gradient pointing towards cell
- K (a lot less): enhancing K exiting cell to lower membrane potential by making it more negative, further away from threshold
- Mg (a bit more): interacts with Na channels to reduce permeability and excitability
- Amino Acids, Protein (less): in brain are neurotransmitters (ie glutamate and glysin are amino acids so we want to control that)
To control/reduce excitability to avoid seizures
CSF Flow
CSF constantly produced by ____ ____ -> circulates through ventricles/central canal of spinal cord and exits and removed from brain through (1) -> moves through _____ space -> top of brain -> exits and drains through (1) to the (1) -> leaves brain and back into circulation
- Median and right lateral aperatures connect ____ to _____
Purpose of constant circulation = maintains ____ of CSF in optimal place (O2, CO2, ions, glucose)
Choroid plexus -> Median or Right lateral aperatures -> subarachnoid -> arachnoid granulations -> sinus vein
- ventricles to sub-arachnoid space
maintains optimal composition of CSF
Structure of BBB
- (1): of the brain capillary endothelial cells
- So to get out of the capillary has to cross the two membranes of the endothelial cell
- Moves freely through -> Water, CO2, O2
- Na, Glucose -> needs channels to move through
- (1): made up of glycol proteins and connective tissue
- (1):
Mostly composed of plasma membrane -> therefore things that are ____ soluble can passively diffuse through theses membranes - drugs that have SE of sedation/any effect on brain function -> can cross BBB
- Tight junctions
- Basement membrane
- End feet of Astrocytes
lipid
Pathophysiological Alterations leading to Neuronal Injury during Bacterial Meningitis
- The part of the inflammatory response that causes vasodilation and increased permeability ______ the _ _ _ and increases fluid within the cerebrospinal space -> cell swelling -> cerebral edema, inflammation in vasculature -> decreased cerebral _____ and ischemia
- ____ disrupts normal metabolism within brain -> increased _____ (low pH) -> more vaso____ -> increase in cerebral blood volume -> increased ____
- Overall, lots of factors that compromise BBB and increase brain swelling, ICP, and decrease perfusion -> if infection not treated can result in cerebral _____ and death
- disrupts the BBB, decreased perfusion
- ROS -> acidity, vasodilation, increased ICP
- herniation
Reticular Activating System
= meshwork of neuronal cells that do 2 things and determines level of _____ _____ (specifically linked to loss of consciosness)
- Receives _____ input from body from ____ and spinal nerves
- _____ sensory info to brain
cortical arousal
- afferent input from cranial/spinal nerves
- Relays info
Glasgow Coma Scale
(3)
- ____ to pain (decorticate) is better than ____ to pain
- Max score =
- Dead body =
Eye Opening
Verbal response
Motor response
- Flexion better than extension
- 15
- 3 (nobody gets a 0)
Characteristic Physical Changes in Alzheimer’s Disease
(3)
- Brain Atrophy (shrinkage)
- Amyloid Plaques (intracellular): inside the axons of neuronal cells, amyloid protein is the basic structural protein that starts accumulate and form plaques
- Neurofibrillary Plaques (extracellular): distortions of axonal structure, looks like physical tangles of axons caused by abnormal production of tau proteins in the microtubules of these axons
Parkinson’s Disease
- Basal Ganglia =
- Parkinson’s particularly effects the ____ ____ (part of spectrum of disorders called parkinsonianism): progressive lack of _____ in part of ganglia called the ____ _____ (black substance) - dopaminergic cells usually stain dark
- Classic Parkinson’s: _____ (slowing down of motor function dt increase in inhibitory acetylcholine), _____ (tend to get worse during purposeful refined movements), R______, P_____ _____
- Processes motor commands from the primary motor cortex and refines that command (removes excess stimulation to muscle, and refines the movement by balance of dopaminergic stimulation and acetylcholine providing inhibition
- basal ganglia, lack of dopamine, substantia nigra
- Bradykinesia, Tremors, Rigidity, Postural Instability
Demyelinating Diseases
Multiple Scerlosis
=
- As axons get demyelinated, what happens to action potentials?
- Imaging will show?
Autoimmune, Demyelinating condition where the myelin that provides insulation to axon fibers in peripheral and central nervous system gets attacked specifically at the myelin fatty acids
- Don’t get to the end of the axon, production is slowed
- Lesions where loss of myelination occurred
No cure for MS: once disability is there, can’t recover it, we can however slow progression (ex keto diet)
Relapsing/Remitting MS (RRMS)
How common?
=
85% of cases
Characterized by discrete attacks that generally evolve over days to weeks (rarely over hours). There is often complete recovery over the ensuring weeks to months. However, when ambulation is severely impaired during an attack, approximately half will fail to improve. Between attacks, pts are neurologically stable.
Mass majority in this category, loss of function then recovers fully back to baseline in early stages but in later stages will have lingering disabilities with every relapse until disability is permanent
Primary Progressive MS (PPMS)
How Common?
=
15% of cases (second most common)
These patients do not experience attacks but only a steady functional decline from disease onset
Secondary Progressive MS (SPMS)
How Common?
=
For those with RRMS, risk of SPMS ~2% each year, meaning majority ultimately evolves into SPMS
Always begins as RRMS, at some point changes so that pt experiences steady deterioration in function unassociated with acute attacks (which may continue or cease during the progressive phase). SPMS produces greater amount of fixed neurologic disability than RRMS
disease starts like RRMS then converts into progressive disease pattern (and in progression may experience 1 or 2 relapses)
Progressive/Relapsing MS (PRMS)
How Common?
=
~5% of MS pts
Overlaps PPMS and SPMS, have steady deterioration in their condition from disease onset. However like SPMS pts, will experience attacks superimposed upon their progressive course
progressive + frequent relapses on top of progressive loss of function
Afferent Components of a typical Peripheral Nerve
There are actually 2 C fibers: one goes to the (1) of the spinal cord and one goes into the (1) where _____ nerves project into
- Dorsal Horn C Fibers =
- Sympathetic Chain C Fiber =
dorsal horn, sympathetic ganglionic, autonomic
- somatosensory and convey and painful stimulation from surface of skin to which we are conscious of that
- is a visceral afferent fiber that conveys visceral pain and stimulation (ie death of myocardial tissue that triggers inflammation and pain)
Direct Activation
Direct activation by intense _____ and consequent ____ damage. Cell damage induces lower __ (H+) and leads to release of (1) and to synthesis of (2).
Prostaglandins increase the _____ of the terminal to _____ and other pain-producing substances.
pressure, cell damage, lower pH -> potassium -> prostaglandins (PG) and bradykinin (BK)
Prostaglandins increase sensitivity of terminal to Bradykinin
Secondary Activation
Impulses generated in the stimulated terminal propagate not only to spinal cord but also to (1) where they induce the release of _____ including (1).
Substance P causes _____ and neurogenic ____ with further accumulation of (1)
Substance P also causes release of (1) from (1) and (1) from (1)
other terminal branches, peptides, substance P
vasodilation, edema, bradykinin
histamine from mast cells, serotonin (5HT) from platelets
Referred Pain
=
Mechanism:
- Predictable areas of referred pain
- Liver/Gallbladder pain =
- Heart =
- Colon =
- Small intestine =
The spatial displacement of pain sensation from site of injury that produces it - visceral pain that is felt on an area on the surface of the skin
Covergence theory: C fibers converge with somatosensory nerves in spinal cord and is perceived by brain as pain that originates in say the kidney is also pain coming from corresponding surface of the skin (dermatome of that spinal nerve)
- Right shoulder
- Left chest, arm, jaw
- mid abdomen
- epigastric region
Ascending Pathways for Pain
Noxious stimuli activates the ____ ending of the primary ____ nociceptor. The message is then transmitted to the ___ ____, where it synapses with cells of origin of the major ascending pain pathway, the ______ tract
- The message is relayed to the (1) and on to
- Somatosensory Cortex (SS) =
- Anterior Cingulate (C) and Frontal Insular (F) =
Peripheral, primary afferent nociceptor, spinal cord, spinothalamic tract
- contralateral thalamus
- pure sensory aspects of pain (location, intensity, quality)
- affective or unpleasant emotional aspects of pain (suffering)
Pain Modulation
Pain Modulation Network: descending pathway that explains why pain is ____ experience due to memory/fear, expectation
- Inputs from frontal cortex and hypothalamus activate cells in the ____ that ultimately control spinal pain-transmission cells
- The pain relieving effects of things like ____ (diverting attention) or suggestion seem to also work through this circuit
- Each of the components of the pathway also contain (1) that are thought to be the targets of (1)
- All components also contain _____ opioid peptides (enkephalins, B endorphin) suggesting an (1) pathway.
Subjective
- midbrain
- distraction
- opioid receptors, opioid drugs
- endogenous, endogenous opioid analgesic pathway
