Pathophysiology of the CNS Flashcards
Muscular Dystrophies (3)
- inherited group of progressive myopathic disorders resulting from defects in a number of genes required for normal muscle function.
- Results from a defect in genes that regulate normal muscle function
- Wide variety of muscular dystrophy, most common is Duchenne and Becker
X-linked inheritance of muscular dystrophies
- Duchenne and Becker muscular dystrophies
* Most common form of muscular dystrophy - Emery-Dreifuss muscular dystrophy (EMD gene)
Duchenne Muscular Dystrophy (DMD)
Caused by a defective gene located on the X chromosome that is responsible for the production of dystrophin.
Dystrophin (4)
- A protein that is located on the cytoplasmic face (inner side) of the plasma membrane of muscle fibers, functioning as a component of a large, tightly associated glycoprotein complex.
- It functions to stabilize the muscle fiber
- Provides a mechanical reinforcement for the structure of the muscle fiber and prevents it from breaking down
- When dystrophin is absent or impaired, you end up with a muscle fiber that is vulnerable to breaking down and digestion by proteases
Absence of Dystrophin
It normally provides mechanical reinforcement to the sarcolemma and stabilizes the glycoprotein complex, thereby shielding it from degradation.
In it’s absence…
the glycoprotein complex is digested by proteases. Loss of these membrane proteins may initiate the degeneration of muscle fibers, resulting in muscle weakness.
Clinical Course of DMD (8)
- Usually asymptomatic at birth. → not recognized at birth but could be predicted
- Postural muscles of the hip and shoulders are usually first affected
- The small muscle groups that help stabilize the hips and the shoulders
- As the disease progresses, you then see some clear changes in posture, ability to walk normally, etc.
- Pseudohypertrophy of the calf muscles eventually develops.
- Signs of muscle weakness become evident by 2-3 y/o
- Imbalances between agonist and antagonist muscles lead to abnormal postures and development of contractures/joint immobility.
- Mortality usually occurs in young adulthood as a result of respiratory or cardiac complications (life expectancy ~30 years old)
Contractures with DMD (4)
- Every muscle has a counter-part muscle; as the two muscles start to become more imbalanced you see posture changes and the development of contractures
- Common contracture = hand contracture; the fingers get curled inward
* When this occurs, you are seeing that the strength of the muscles in the palm are much greater than the strength in the back of the hand - Strength of pulling in the joints and the joints get immobilized/frozen in place
* This affects the use of the hand (or the use of whatever limb is affected) - Contractures can get so bad that often times there is physical therapy necessary to counteract the tendency toward the contracture; usually to relax the stronger muscle group to prevent the contracture from occurring
* If contracture is very bad you can dislocate the joint in trying to relax the contracture
Clinical Manifestations of DMD (8)
- Changes in posture and ability to walk normally
- Pseudohypertrophy of the calf muscles
- Muscle Weakness
- Contractures and/or joint immobility
- Scoliosis is common
- Use of wheel chairs will become necessary around 7-12 years old
- Respiratory muscles often involved and results in weak and ineffective cough, frequent respiratory infections, and decreased respiratory reserve
* Leaves them vulnerable to resp. infections and resp. problems - Cardiomyopathy is common
***Smooth muscle of bladder and bowel and preserved
Common Features of DMD (6)
- Contractures in hands
- Change in posture with curvature of the back because postural muscles in shoulders and hips are affected
- Belly protrudes due to weak abdominal muscles
- Shoulders and arms are held back, especially when walking
- Knees can hyperextend or bend backwards
- Calf muscles can appear quite large → this is called pseudohypertrophy because the muscle has mostly been replaced by fat
Sensation with DMD
Sensation is completely preserved, so this patient can feel uncomfortable in the position their body is in but not be able to do much about changing it
Primary Head Injury
whatever physically occurred to the brain
*Ex: blunt force injury or penetrating injury
Secondary Head Injury
Occurs as a result of brain swelling and the release of intracellular substances with cell death
Intracellular Substances Released with Secondary Injury
Intracellular substances include ions and NTs → release of these creates an increase of excitability of the surrounding cells and uncontrolled excitability through the brain leads to seizures
- This always occurs with traumatic head injuries
- Often times it can cause just as much if not more harm than the primary injury
Brain Swelling with Traumatic Head Injury (3)
- Significant problem because the skull doesn’t stretch
- When brain swells in intact cranium → increase in ICP, which can lead to seizures
- If ICP gets too high, the most life-threatening complication will be herniation, where the brain is allowed to expand and the only place where there is room is the foramen magnum (the opening at the base of the skull where the spinal cord comes out)
* Pushing of the brain through foramen magnum
Brain herniation
Brain stem is right above foramen magnum, so brain stem gets shoved through it with herniation and it is immediately fatal.
Focused treatment of TBI
avoiding secondary injuries at all cost
Traumatic Head Injuries Can Cause… (5)
- Skull Fractures
- Parenchymal injury (TBI)
- Focal Brain Injuries
- Diffuse Brain injury (diffuse axonal injury)
- Traumatic Vascular Injury
Parenchymal injury (TBI)
all forms of TBI can involve both a primary (first injury) and secondary (brain swelling, release of intracellular ions/transmitters)
Focal Brain Injuries
Contusions and Lacerations
- Focal injury that is non-penetrating will cause a contusion
- Focal injury that is penetrating will cause a laceration
Diffuse Brain Injuries
Concussion
- Caused by rapid deceleration of the brain
- Hit on the head and the brain moves back and forth very quickly and hits the skull
- Brain is attached to the top and swings; when your head goes forward, the brain swings back and vice versa
- Non-focalized injury = the concussion
Traumatic Vascular Injuries (5)
- Hematomas
- Epidural
- Subdural
- Subarachniod
- Intraparenchymal
Mild Concussion
temporary axonal disturbances
*The axons get stressed and the function flickers
Grade I and II Concussion
some disturbance in attention or memory but no loss of consciousness (foggy headed)
*With each grade, the axon injury gets worse an worse until sustained lose of function
Grade III Concussion
may involve brief loss of consciousness (less than 5 minutes)
Grave IV Concussion (4)
- Classic Cerebral Concussion - an immediate loss in consciousness that lasts more than 5 minutes but less than 6 hours
- Substational injury but patient will wake up w/i 6 hours
- Any loss of consciousness involves disruption of RAS (whether it is grade 3 or 4)
- Involves temporary disruption of the Reticular Activating System (RAS)
Reticular Activating System
- RAS relays all the sensory information coming up to the brain
- All the sensory info coming into the brain is constantly being relayed to the cerebral cortex
- Some of it is conscious in input; if you thought about it you could name sounds and sensations that are going on, but there are also a lot of unconscious sensory information
- All of this input coming to the brain by the RAS determines the level of cortical arousal that you have
- All the background noise that keeps the brain awake
Disruption of RAS
- All of a sudden everything goes dark and you appear to fall asleep (lose consciousness)
* Brain is still working, but there isn’t enough cortical arousal for you to be switched on
Ex: in grade 3, there may be a 30 second switch off of cortical arousal
- With classic cerebral concussion it will take 5 min or more for RAS to come back
* Descending info is still occurring, but ascending is not
When is head injury an emergency?
If they don’t immediately lose consciousness but lose consciousness later it is an
Immediate LOC is potentially OK, but any LOC that isn’t immediate is a huge problem because it can suggest bleeding in the brain and can be imminent death
*Sleep isn’t dangerous but can’t monitor LOC when they’re asleep, so you want to keep them up to monitor their sleep post-concussion
Coma
If the concussion is severe enough that the patient isn’t waking up w/i 6 hours, they are in a coma
Chronic encephalopathy
Can occur due to multiple concussions
Hematoma
- Significant complication because when bleeding occurs in the brain it will cause a rise in ICP quickly
- Can be fatal quickly
- An example of damaged blood vessels deep within the brain are a result of some acceleration and decerlation injuries in very small children
Postmortem way to confirm child abuse
if there is intracranial bleeding, because shaking a child vigorously can cause intracranial bleeding or bleeding to death
Epidural Hematoma (6)
- Epidural hematoma has bleeding between the cranial bone and the first meningial layer (the dura matter)
- The most common cause is laceration to the middle meningial artery
- A large artery that runs just under the cranial bone over the side of the brain
- A laceration of this will cause bleeding in the epidural space
- LOC is a secondary injury
- The only way to deal with the hematoma is to burrow a hole in the cranium to let the blood come out and release pressure
Subdural Hematoma
- Bridging veins that extend across to the superior aspect of the cerebral hemispheres
- The most common cause of a subdural hematoma is bleeding from a set of veins called the bridging veins
Bridging Veins
These veins drain blood away from the brain and drains into a large vein called the saggital sinus (at the top of the cranium)
*The bridging veins bridge the space between the brain and the saggital sinus, and run through the dura matter
Populations vulnerable to Subdural Hematoma (2)
- Elderly patients with any degree of brain atrophy
* More tension on the bridging veins due to the reduction of brain size - Very small children (babies, etc.)
* They have thinner, more delicate bridging veins
**Both of these patient populations are vulnerable to abuse
Acceleration/Deceleration injury can lead to…
it can cause tearing of the bridging veins and that can cause bleeding beneath the dura matter and a subdural hematoma
Bleeding in the subdural space increases ICP → can become fatal quickly
Thrombotic Stroke (3)
- Cause of thrombosis is secondary to atherosclerosis
- Have an atherosclerotic plaque in a cerebral artery, it ruptures, and you get a superimposed thrombos on top
- Same risk factors for cardiovascular disease, etc.
* *Hyperlipidemia, smoking, hyperglycemia, HTN
Embolic Stroke (3)
- The most common scenario is a clot that forms on the left side of the heart and then leaves the heart and travels up to the brain and blocks a cerebral artery
- Can cause a pocket of stagnant blood flow behind the valve, which can cause the clot to form
- Leading cause of embolic stroke clot formation on left side of heart= atrial fibrillation
* Atria of heart instead of contacting at the beginning of the cardiac cycle will just quiver; the blood stagnates and increases the likelihood that the clot will form
Hemorrhagic Stroke (4)
- Caused by a break in a blood vessel or artery in brain leading to hemorrhage
- You may see a cerebral aneurism in the brain that ruptures
- Will cause global cerebral ischemia as opposed to focal ischemia
- High mortality rate
Lacunar Stroke (3)
- Very specific sub-type of thrombotic stroke; they affect tiny vessels in mostly the brainstem
- Can go unnoticed until a critical number of them occur
- Appearance is “lake-like” → when you look at the pons postmortem there are tiny thrombi in the vessels
3 major parts of brain important for voluntary motor function
- Primary Motor Cortex
- Basal Ganglia
- Cerebellum
Primary Motor Cortex
All voluntary motor movements originate in the primary motor cortex
Primary Motor Cortex and Stroke (3)
- Any thrombotic or embolic stroke that affects blood flow to primary motor cortex will cause impaired motor movement to that part of the body
- If the location of the focal ischemia is on the left side of the brain, the impairment of motor function will be on the contralateral side
- Will usually see unilateral loss of function
Basal Ganglia
Modifies motor movements
Cerebellum
Modifies motor movements
Somatosensory Cortex
Where all the conscious sensation is perceived
Somatosensory Cortex and Strokes
Any thrombotic or embolic stroke that affects blood flow to primary motor cortex will cause impaired motor movement to that part of the body
*If the location of the focal ischemia is on the left side of the brain, the impairment of motor function will be on the contralateral side
Wernicke’s Area (5)
- Processes auditory input for language – important for understanding speech
* The language master - Takes in numerous cues and makes sense of them/interprets them
- Communicates with Broca → Broca decides what we say → Broca contacts primary motor cortex because we have to move our lips and mouth to speak
- Connection between Broca and Wernicke’s is bi-directional; meaning we can have an inner dialogue
Damage to Wernicke’s Area
May still be able to communicate but comprehension of what people tell you may not be there
Angular Gyrus
- Part of the temporal lobe – combines auditory input from the primary auditory area and other senses from the somatosensory cortex and visual cortex and feed into the Wernicke’s area
- Receives auditory input and takes in input from the visual cortex (non-verbal cues for language)
* We value visual cues more than auditory! - All of this gets fed into Wernicke’s area
Injury to Angular Gyrus
Not using all cues available to interpret what you’re saying
Broca’s Area
receives input from Wernicke’s area and controls the production of intelligible speech – lies near the primary motor area that controls the tongue movements that form words – the connection between Broca’s and Wernicke’s area is bidirectional to facilitate the integration of speech formation, comprehension, and editing.
Injury to Broca’s Area
comprehend what people are saying but can’t communicate
Four Key Features of Stroke
- Sudden onset
- Focal involvement of the CNS
- Lack of rapid resolution
- Vascular cause
Lack of rapid resolution with stroke
The duration of neurologic deficits is documented by the history. In the past, the standard definition of stroke required that deficits persist for at least 24 hours to distinguish stroke from transient ischemic attack (discussed later). However, any such time point is arbitrary, and transient ischemic attacks usually resolve within 1 hour.
Vascular Cause of Stroke
A vascular cause may be inferred from the acute onset of symptoms and often from the patient’s age, the presence of risk factors for stroke, and the occurrence of symptoms and signs referable to the territory of a particular cerebral blood vessel. When this is confirmed by imaging studies, further investigations can be undertaken to identify a more specific etiology, such as arterial thrombosis, cardiogenic embolus, or clotting disorder
Acute onset of strokes
Strokes begin abruptly. Neurologic deficits may be maximal at onset, as is common in embolic stroke, or may progress over seconds to hours (or occasionally days), which may occur with progressive arterial thrombosis or recurrent emboli.
Transient Ischemic Attack
produces neurologic deficits that resolve completely within a short period, usually within 1 hour.
*There is a sudden onset
Ex: could see sudden loss of speech but then it resolves quickly
Represents temporary loss of blood flow to an area but then quickly resumes blood flow to the area
Stroke-in-evolution (5)
- Progressing stroke, causes deficits that continue to worsen even as the patient is seen.
- Progressive decline in function
- Plaque rupture and small clot forms then gets bigger → impairs more and more blood flow over time
- Blood flow to the area is worsening as the clot increases in size
- Not as common
Completed Stroke
Defined by the presence of persistent deficits, which may be stable or improving when the patient is seen; it does not necessarily imply that the entire territory of the involved vessel is affected or that no improvement has occurred since the onset.
Classic Stroke
sudden onset and the impairment persists/doesn’t get better
*The symptoms may resolve when they get treated, but until they get treatment the loss of function persists
Common Symptoms/Signs of Stroke (10)
- Headache
- Altered LOC
- Aphasia
- Visual field deficit
- Dipolopia
- Vertigo
- Dysarthia
- Drop attacks
- Hemi or monoparesis
- Hemisensory deficit
Consicousness
The state of awareness of self and environment and of being able to orient to new stimuli
- Spontaneous wakefulness = important part of LOC
- 3 levels of orientation: person, place, time
Two Components of Consciousness
- Arousal and Wakefulness - requires concurrent functioning of RAS and cerebral cortex
- Content and cognition - requires functional cerebral cortex
Content and Cognition
more than just awake, there is content and thought and with there is actual cognition that you’re capable of (ex: 2+2=4)
*Requires cerebral cortex
Arousal and Wakefulness
Requires the function of both the cerebral cortex and the RAS
*In the case of a concussion patient that immediately loses consciousness and remains unconscious → that patient loses arousal and wakefulness due to temporary loss of function of RAS; They may have content and cognition, but not arousal and wakefulness until RAS comes back
What happens when someone sustains an injury that may involve more substantial injury to the brain, such as to the cerebral cortex + a coma
whether or not they are awake depends on damage to cerebral cortex, because eventually RAS may come back online but if cerebral cortex suffers enough damage then they won’t get out of the coma
Confusion
Impaired ability to think clearly and to perceive, respond to, and remember stimuli (disorientation)
Delirium
Motor restlessness, transient hallucinations, disorientation, and sometimes delusions
*acute onset, different from dementia
Obtundation
Decreased alertness with associated motor retardation
Stupor
Conscious but with little or no spontaneous activity
*person seems asleep but you can rouse them
Coma
Unarousable and unresponsive to external stimuli or internal needs
*often determined by Glascow Coma Scale
Glascow Coma Scale Parameters (3)
- Eye Opening
- Verbal Response
- Motor Response
Maximum score = 15
Motor response flexion to pain
represents pre-profound brain damage
Motor response extension to pain
which suggests a loss of communication; worse than flexion to pain
Localises to pain
The patient becomes wakeful and can localize the pain enough to try and push the hand away
*Not only wakeful to pain but clear signs they can see where the pain is coming from
Brain Death Definition and clinical examination
Definition: the irreversible loss of function of the brain, including the brain stem.
Clinical examination must disclose at least the absence of responsiveness, brain stem reflexes, and respiratory effort (repeat evaluation after 6 hours is recommended and use of EEG testing)
What occurs with brain death (4)
- There is an absence of respiratory function, an absence of any kind of brain stem reflexes
- Total absence of spontaneous respiratory effort
- If an EEG test is performed you find no brain activity
- But what you will see is if patient is mechanically ventilated and the heart receives enough oxygen, the heart continues to pump
Persistent Vegetative State
characterized by loss of all cognitive functions and unawareness of self and surroundings. Reflex and vegetative functions remain.
*For patients who don’t wake from a coma relatively soon, most will progress into this persistent vegetative state
Characteristics of Persistent Vegetative State (5)
- Reflex and vegetative functions are maintained
* The patient’s spinal reflexes, etc. are maintained - Basic body functions, cardiovascular function, etc. are all maintained but there is no cognitive awareness or awareness of self or environment
- Inability to interact with others, etc.
- absence of sustained or reproducible voluntary behavioral responses
- Lack of language comprehension, bowel and bladder incontinence, non-oral feeding, and variably preserved cranial or spinal reflexes
lasting at least 1 month
Feeding and Persistent Vegetative State
Cannot consume food by mouth, so feeding requires a G-tube
*Whether or not a G-tube gets inserted is a decision that the patient has hopefully made before being in this position, otherwise it is left to the next of kin
Minimally Conscious State
when patient’s do have periods of time where they seem to be aware of self and oriented to their environment
*They have clear documented times of communication with others, but it isn’t consistent
Locked In Syndrome
They have consciousness (patient is aware) but their motor impairment that is so profound that they can’t communicate
