Block 4 Flashcards
What is the brain? What are the three main functions of the central nervous system?
the brain is an information processor that interfaces with the environment: condition, stimulus, receptor, signal, integration, signal release, effect (motor function)
Brain + Spinal Chord
input–>process–>output
1. input: receptors convert the environment into electrochemical signals for processing by the brain
2. cognition: interpretation
3. output: motor movement
What are the three sectional planes used to examine the brain?
- frontal plane (coronal)
- sagittal plane (side)
- transverse plane
What is the hippocampus?
critical region for new memory formation; often affected in neural degeneration; looks like a seahorse
What happened to HM?
- bilateral medial temporal lobe removal from epilepsy
- developed anterograde amnesia
- moderate retrograde amnesia
Difference between anterograde and retrograde amnesia?
not able to form new memories vs. loss of memory access to events from the past
List the anatomic levels of the CNS
- Telencephalon: cerebral hemispheres, hippocampus
- Diencephalon: thalamus
- Cerebellum
- Brainstem: midbrain, pons, medulla oblongata
- Spinal chord
What is a lesion? How are they organized?
any pathology finding that affects function
1. focal brain disorder: localize pathology to a focal area of the brain
2. Diffuse brain disorder: many areas involved and can’t localize; causes encephalopathy –> from primary brain disease or secondary to metabolic disease
Break down the sections of the brain
2 cerebral hemispheres: dominant is opposite side of handedness
- language problems localize here
4 lobes per hemisphere
1. Frontal: motor cortex (motor homunculus), speech (Broca’s Area), executive function
2. Parietal: somatosensory cortex
3. Temporal: auditory cortex (Wernicke’s dom side), memory (hippocampus)
4. Occipital: visual cortex
Parts of the brain you have to know
- basal ganglia: initiation and coordination of movement
LESION: movement difficulties, PK, HT disease
CLINICAL: tremor, rigidity; hypokinesia, hyperkinesia - thalamus: sensory relay station of the brain
LESION: inability to feel things, hemorrhagic stroke in
hypertension - brainstem: cranial nerves, consciousness, cardiorespiratory function
LESION: impaired movement, death from intracranial pressure - cerebellum: balance and posture
LESION: ataxia = incoordination or clumsy movement (alcohol)
What happens where there is focal injury to the dominant frontal lobe?
aphasia: disorder or speech
Broca’s: problem of speech production (BROKEN)
motor cortex: inability to coordinate movement
PFC: impaired cognition, mood changes
What happens when there is focal injury to the parietal lobe?
dominant: apraxia = difficulty in performing a complex learned action
non-dominant: neglect of the opposite side (person is unaware of half their body)
What happens when there is focal injury to the temporal lobe?
damage to hippocampus: amnesia
dominant: Wernicke’s area, verbal learning
non-dominant: visual learning, face recognition =prosopagnosia
What happens when there is focal injury to the occipital lobe?
visual deficits, blindness
What are the cells of the CNS?
Neurons
- acute: red-dead neurons
- chronic: neurodegeneration: progressive loss of synapses, neurons, gliosis, atrophy
1. astrocytes: physical support, repair, reactive gliosis (proliferation/fibers/scarring) in response to injury
2. oligodendrocytes: myelinate CNS neurons-> myelin insulates axons; swelling, loss (MS), inclusion (viral infection) during injury
3. microglia: immune cells of CNS, phagocytic, release immune mediators in response to injury
4. Ependymal cells: help produce, circulate, and absorb CSF; dysfunction leads to hydrocephalus
5. Schwann cells: promote axon regneration
What are the challenges neurons face?
large cell size, metabolically active, long-lived, highly polarized, long cell processes, functionally diverse
Difference between acute, subacute, and chronic?
acute: seconds to hours
- focal: vascular (stroke), seizure (focal), trauma (contusion)
- diffuse: vascular (SAH), seizure (generalized), trauma (DAI), metabolic (hypoglycemia)
subacute: days to weeks
- focal: infection (abscess), inflammation (MS), auto-immune
- diffuse: infection (meningitis), inflammation (AI encephalitis)
chronic: months to years
- focal: neoplasm (GBM)
- diffuse: degenerative, metabolic
When is the lesion? Where is the lesion? What is the lesion?
- acute, subacute, chronic
- which of the 5 CNS levels or more than 1
- focal, multifocal and diffuse
What is hydrocephalus? What is edema and its causes?
increased CSF volume leads to expansion of the ventricles and increase intracranial pressure
1. Too much CSF being made (ie: tumor of cells that make CSF)
2. CSF flow is obstructed (ie: tumor/anatomy blocking ventricles)
3. CSF is not being reabsorbed (ie: meningitis with residual scarring)
too much fluid in brain tissue leads to increased intracranial pressure, fatal brain herniation
1.) vasogenic: abnormal increased permeability from breakdown of BBB
2.) cytotoxic: direct cell injury and swelling
3.) hydrocephalic: breakdown in ventricular lining
common after complete cessation of blood to brain
What are the lethal reactions?
hemorrhage, herniation, hydrocephalus, hypoxia
Herniation? Hemorrhage?
complication of RICP: brain expands into other structures, affecting blood flow; midline shift
1) subfalcine: anterior cerebral artery
2) transtentorial: posterior cerebral artery; causes duret hemorrhage: fatal upper brainstem
3) WORST: tonsillar ‘coning’, compresses brainstem = death
What kills people with intracranial disease?
- RICP due to mass lesion: hydrocephalus, hemorrhage, or other lesions; herniation with brainstem compression and Duret hemorrhage
- Cerebral ischemia: problem of arterial blood supply
- occlusion or rupture of vessel: stoke, aneurysm
- malformation of vessel: AVM
- compression of vessel - cerebral hypoxia: neurons are not getting oxygen
- brain ‘poisoning’: toxic substances lethal to neurons
How is the CNS assembled? What happens when there is failure?
neurulation is the process of neural tube closure and CNS formation
neural tube defects:
-anencephaly: absence of brain
-myelomeningocele: spine is exposed
- encephalocele: brain protrudes through a midline skull defect
Diagnostic techniques?
- CT scan: first pass; bleeds, abscess, edema, changes to ventricles
- MRI: more detail about brain structure, strokes, tumors, trauma, MS
- Angiogram: blood vessels (bleeds, occlusions, aneurysms, malformations); invasive with contrast
- EEG: brainwave activity, useful for seizures
- Lumbar puncture: analyze CSF to look for RBCs/WBCs that would tell us about bleeding, infections, tumors
- biopsy: gold standard to look at brain under microscope; tumor diagnosis/prognosis
- neuropsychological testing: cognition
- autopsy: cause of death
What is the MCA?
middle cerebral artery: major artery of the cerebrum
supplies most of motor cortex and motor homunculus
What is a stroke? Causes? Risk Factors?
sudden damage to the brain of vascular origin; lack of blood flow -> cell death
caused by ischemia or bleeding
- cerebral infarct caused by atherosclerosis
- intracranial hemorrhage
- subarachnoid hemorrhage
hypertension, diabetes, high cholesterol, smoking, history, alcohol/drugs
ischemic (80%): usually atherosclerosis (plaque)
hemorrhagic: hypertension (DEEP in brain) or superficial (amyloid, AVM = high pressure vascular anomaly)
paralysis, weakness, numbness
develop over time, present acutely
What is amyloid angiopathy?
abnormal beta amyloid protein deposits in the blood vessel walls; superficial acute lobar hemorrhage
sporadic: age-associated, common with AD
familial: mutations in AB
What is an aneurysm? Risk factors?
focal pathological swellings of a blood vessel; sudden onset ‘thunderclap headache’
factors: size, location, morphology
ruptured aneurysm cause of SAH
hypertension, cocaine, pregnancy, trauma, history
What is an arteriovenous malformation?
high-pressure vascular abnormality; tangled network of arteries and veins lacking a capillary bed
bleeding is the most common presentation; usually in cerebral hemispheres
What is an abscess?
pus-filled swelling in the brain; necrosis and inflammation caused by infection; subacute lesion
can expand or rupture; can be multifocal = source of infection is in the bloodstream or they are immunosuppressed
headache, fever
‘ring-enhancing lesion’ = abscess, lymphoma or glioblastoma
Focal chronic brain lesions?
primary brain neoplasms = tumors = excessive abnormal tissue growth; compress blood vessels, increase ICP with edema/inflammation; can be multifocal; rarely metastasize
1.) intra-axial = brain + spinal chord: glial
astrocytoma, glioblastoma, oligodendroglioma, medulloblastoma
2.) extra-axial = CNS accessories (nerves, bone): not glial
meningioma, Schwannoma, pituitary adenoma
What are the categories of gliomas?
circumscribed: good margins; surgery works
diffuse: infiltrating margins; can’t be removed with surgery
primary: older patients, de novo, EGFR amplified, IDH WT
secondary: younger patients, IDH driver mutations
What is the most common CNS tumor?
meningioma: benign tumor of meningothelial cells; external surfaces of the brain; slow-growing; most common in women; NF2 gene mutations
CLINICAL: headache, nausea/vomiting, blurred vision
causes: sporadic, irradiation
Metastatic brain tumors?
~25% of tumors
usually carcinoma, melanoma, lymphoma
Top cause = lung
Common malignant brain tumor?
glioblastoma: found in cerebral hemispheres
butterfly patterning on imaging
What do diffuse brain lesions cause?
encephalopathy: any diffuse brain disorder that alters brain structure or function
- ALTERED MENTAL STATE (AMS): confusion, delirium, dementia, concussion, coma, loss of consciousness
- acute, subacute, chronic
- symmetric across brain
Secondary encephalopathy?
caused by disturbances outside the brain
- organ failure
- nutritional deficiencies
- diabetes: hyperglycemia
- disturbances of water and Na balance
- sepsis
ex) hepatic encephalopathy = liver failure due to cirrhosis
ex) hypoxic-ischemic from cardiac arrest
What are multifocal brain lesions?
separation in space and time
- vascular: multiple infarcts, vasculitis
- infectious: multiple abscesses = bacterial endocarditis
- tumor: multiple metastases, multifocal primary tumor (glioblastoma), tumor predisposition syndrome (NF2)
What is MS?
multiple sclerosis: multifocal demyelinating disorder of the brain; autoimmune response targeting the myelin sheath causes selective demyelination; plaques
25-35 years old; optic nerves, brainstem, spinal chord are commonly affected
Diffuse acute lesions?
- Trauma: diffuse axonal injury, traumatic brain injury
- Vascular: subarachnoid hemorrhage
- Metabolic: hypoglycemia
- Seizure (generalized)
Diffuse subacute lesions?
infection: meningitis, encephalitis
- HSV, PML, bacteria
inflammation
Diffuse chronic lesions?
metabolic: alcohol, central pontine myelinolysis, fetal alcohol syndrome
neurodegenerative: dementia, motor neuron disorders, movement disorders
Describe TBI?
- # 1 cause of death in people <45 years old
- can be focal or diffuse: immediate AMS tells us diffuse
- primary: immediately at impact
- secondary: 4 H’s
Describe DAI?
axotomy (neurons separate) with formation of spheroids
risks: hypoxia, edema, RICP, herniation, compression of posterior cerebral artery
What is HSV encephalitis?
herpes simplex virus: targets limbic system (cerebral cortex and brainstem that regulates behaviors needed for survival)
CLINICAL: rapid onset fever, headache, impaired consciousness; CSF is abnormal ; EEG has encephalopathy pattern
necrosis, hemorrhage, inflammation –> edema –> RICP –> herniation
What is progressive multifocal leukoencephalitis (PML)?
- caused by JC virus in immunosuppressed patients with focal and diffuse signs over months
- all 3 primary responses to infection (perivascular cuffs of lymphocytes, viral inclusions, microglial nodules) and secondary changes
- demyelination of white matter; focal (visual disturbance, ataxia, seizures) and diffuse (AMS) signs that develop over months
What is a diffuse acute on subacute lesion?
meningitis: inflammation of the meninges and CSF usually caused by infection
- fatal within hours of acute onset
- clinical is diffuse: fever, headaches, neck stiffness, AMS, seizures
- confirmed with blood cultures and lumbar puncture
- meningeal fibrosis can develop after inflammation: focal = optic or cranial nerves –> blindness; diffuse = block CSF reabsorption causing hydrocephalus, AMS, paralysis
What is an acute SDH? How does it relate to chronic alcoholism?
subdural hemorrhage: space occupying lesion that splits the dura from the arachnoid caused by tearing of the bridging veins from motion/impact
- causes midline shift and life-threatening brain compression and herniation
patients with brain atrophy from alcoholism are at a greater risk for SDH from stretching the bridging veins
What are the CNS lesions of chronic alcoholism?
hepatic encephalopathy, trauma, cerebellar degeneration (ataxia, atrophy, <1%), central pontine myelinolysis (CPM), nutritional deficiencies, fetal alcohol syndrome
Hepatic encephalopathy?
major complication of cirrhosis
- confusion, altered consciousness, coma
- asterixis (tremors of hands)
- increased bleeding risk due to liver disease makes brain trauma hard to treat in alcoholics (contusions spread, RICP)
What can chronic alcoholism induce?
mamillary body degeneration: connect hippocampi to other brain regions
Wernicke encephalopathy: global confusion, apathy, disorientation, ataxia
Korsakoff psychosis: retrograde amnesia, anterograde amnesia
What is central pontine myelinolysis (CPM)?
focal demyelination of the pons; not multifocal + has clear cause normally
- alcoholic liver disease is associated with low sodium–> rapid infusion of saline can cause CPM –> rapid onset confusion, quadriplegia
What is fetal alcohol syndrome (FAS)?
most common cause of preventable neurodevelopmental defects
mom maintains high level of alcohol intake during pregnancy
What is acute methanol intoxication?
ingested as a cheap substitute for ethanol, oxidized by the liver to produce formaldehyde that is neurotoxic
loss of vision, AMS, convulsions, coma, death
global hypoxic brain damage; acute hemorrhage in the basal ganglia is common
What is neurodegeneration?
progressive selective neuron loss with LOF in NDDs
- neuronal connections (synapses) are lost during normal ageing
- normal age-related cognitive decline is associated with that than neuronal loss
- synaptic degeneration is associated with abnormal protein aggregation and occurs early in AD
What are the risk factors and hallmarks of NDD?
- ageing: neurons do not divide
- classified by major protein deposit: protein misfolding disorders = ‘proteinopathies’
- neuronal/glial inclusions from misfolded protein accumulation
Which proteins are associated with which NDD?
AD: amyloid beta, tau
ALS: TDP-43
PK: synuclein
What are the common features of NDDs?
- age-dependent relentlessly progressive disorders
- affect selectively vulnerable populations of specific neuronal subpopulations
- characterized by the accumulation of abnormal insoluble protein
aggregates in the form of inclusion bodies
What are the 3 groups of NDDs?
- Dementia
- AD, vascular brain injury, Lewy body dementia, frontotemporal dementia - Movement disorders
- PK, HD - Motor neuron disorders
- ALS, spinal muscular atrophy
What is dementia?
persistent cognitive impairment across multiple domains
- loss of previously attained occupational or social function due to acquired and persistent impairment of memory, emotion, personality, or cognition with normal consciousness
What is AD?
most common cause of dementia; slowly progressive diffuse brain disease with global cerebral atrophy
- synaptic and neuron loss from pathological accumulation of tau and AB
- 3 phases: preclinical, mild cognitive impairment, dementia
- dilation of ventricles, atrophy of hippocampus and amygdala
AB and tau protein role in AD?
produced from the amyloidogenic pathway and is neurotoxic
- loss of synapses, impairs mitochondrial function
- APP is on chromosome 21; trisomy 21 have early onset AD
- plaques cause astrocyte and microglia responses
tau protein becomes phosphorylated in AD which forms intracellular tangles (NFTs); destabilize microtubules
What causes AD?
sporadic (>95%): late-onset; age, genetic, environmental
familial: early onset (<60 yo); autosomal dominant
AB plaques and tau neurofibrillary tangles, neuronal and synaptic dysfunction, neurodegeneration –> neuron loss, gliosis, microglial activation, amyloid angiopathy
What is amyloid angiopathy?
Abnormal Aꞵ protein deposits in the blood vessel walls
* Sporadic (age-associated) amyloid = common and is
associated with AD
* Familial causes are uncommon and caused by mutations in Aβ
**can cause lobar hemorrhage
What are the 3 reasons for intracranial hemorrhage in AD?
- lobar hemorrhage from amyloid angiopathy
- subdural hemorrhage from bridging veins stretching from cortical atrophy
- hypertensive hemorrhage from cardiovascular disease (risk factor for AD)
What is parkinsonism?
most common cause is Parkinson disease
- tremor, rigidity, akinesia, postural instability
What is Parkinson Disease?
- selective loss of pigmented substantia nigra neurons
—> motor symptoms of PD are due to decreased dopaminergic stimulation of the striatum - Lewy bodies begin in the brainstem and end in cerebrum; aggregates made of alpha-synuclein protein cause neuron death–> astrocyte and microglial reactions
Lewy body disorders classifications?
brain region affected
LB dementia: cortex/limbic = cognition
PD: midbrain = motor
PD dementia: cortex/limbic + midbrain = cognition and motor
What is Huntington’s Disease?
progressive basal ganglia degeneration with movement disorder and progression to dementia
- autosomal dominant inheritance due to mutations in HTT
- causes hyperkinetic movement
- atrophy of caudate and putamen –> enlarged ventricles
- severe neuronal loss with activated astrocytes and microglia
**greater polyglutamine repeats, earlier age of onset
What is ALS?
amyotrophic lateral sclerosis: progressive loss of motor neurons in the motor cortex, brainstem, and spinal cord
- profound muscle weakness, paralysis, loss of ability to walk, move, breathe
- 100% fatal
- 80% sporadic
-TDP43 cytoplasmic inclusions is hallmark –> neuron degeneration –> activation of astrocytes and microglia
- frontotemporal lobar degeneration
