Neurological Disorders (Exam 1) Flashcards
Three functions of the nervous system
Detect, analyze and transmit information
Communicate through electrochemical signals
Neurons
Somatic and autonomic
Peripheral nervous system
Voluntary movement
Somatic
Involuntary movement (parasympathetic and sympathetic)
Autonomic
Arrive at CNS
Afferent
Exit from CNS (brain and spinal cord)
Efferent
Neurons do not
Divide
Sensory receptor cells to the brain
Sensory neurons
Brain to muscles
Motor neurons
Info between neurons
Interneurons
Modulate and regulate the electrical activity of a given neuron
Neurotransmitter
Electrical signal that travels down the axon and is created using NA and inhibited by K
Action potential
Three basic parts of a neuron
Soma, branching dendrites and axon
Junction between two neurons; passes info between them
Synapse
Open sodium and calcium channels leads to an action potential
Excitatory neurotransmitter
Open chloride channels > hyper polarization > resting potential
Inhibitory neurotransmitter
Resting potential average
-70 mV
Barrier between circulation and the brain (exception: olfactory lobes)
Blood brain barrier
Tight junctions from barriers
Endothelial cells
Structural support, immune properties
Pericytes
Structural support, recruits WBCs
Astrocytes
The BBB is a highly
Selective semipermeable membrane
Role of p-glycoprotein pumps
Remove harmful compounds
Lacks a functioning BBB; contains receptors to detect toxic substances that lead to emesis
Chemoreceptor trigger zone
Dysfunction of the BBB can lead to
Alzheimer’s or Parkinson’s
Most drugs are transported over the BBB via
Passive diffusion
Endogenous substances and amino acid derived drugs cross the BBB via
Carrier mediated
Endogenous substances such as hormones and LDL pass the BBB via
Receptor mediated
Some proteins pass the BBB via
Absorptive transcytosis
Substances pumped out of the BBB via
Active efflux
When a neurotransmitter also functions as a hormone
Neurohormones
When a neurotransmitter also functions as a hormone
Neurohormones
Membrane potential becomes more positive
Excitatory post synaptic potentials
Membrane potential becomes more negative
Inhibitory post synaptic potential
Depolarization approximately to
+35 mV
When potassium gates close slowly
Hyper polarization
When sodium channels close and potassium channels open, potassium flows out
Repolarization
Dopamine, norepinephrine and epinepherine
Catecholamines
Serotonin, dopamine, norepinephrine and epinephrine
Monoamines
Unpleasant sensory and emotional experience associated with actual or potential tissue damage
Pain (physiological)
Short duration and resolves
Acute
Longer than expected of healing; no useful physiological purpose
Chronic (pathophysiological pain)
How many people experience chronic pain at some point in their life?
1 in 3
From tissue damage due to trauma/inflammation; mechanical/temp/chemical stimuli
Nociceptive pain
Pain from musculoskeletal system (skin, bones, muscle, connective tissue)
Somatic
Pain from visceral organs (abdominal pain)
Visceral pain
Cancer can be from what type of pain
ALL TYPES OF PAIN :(
Functional pain
pain with no identified origin
Physiology of Pain (5 steps)
- transduction
- conduction
- transmission
- modulation
- perception
- Transduction (Pain process)
sensory neurons activated to noxious stimuli
- Conduction (Pain process)
action potential travels along the neuron to the spinal cord (A fibers and C fibers)
what are A fibers? what are C fibers?
A fibers - myelinated neurons; first pain
C fibers - unmyelinated fibers; 2nd pain
- Transmission (pain process)
sensory neurons release substances that activate a 2nd neuron in spinal cord and sends a message to the brain
- Modulation (pain process)
pain can be facilitated or inhibited depending on which substances are released
- Perception
complex interaction between ascending and descending pathways and various brain systems
overtime pain pathways become
stronger with repeated pain and leads to pain hypersensitivity
allodynia
pain caused by stimulus that does not normally provoke pain
hyperalgesia
increased response to stimulus that is normally painful
Substances that facilitate pain (3)
- Substance P
- Glutamate
- Inflammatory mediators
substances that reduce pain (4)
- endogenous opioids
- endogenous cannabinoids
- GABA
- serotonin and norepinephrine
Primary headache disorders
not due to another cause
primary headache examples (3)
- tension
- migraine
- cluster
secondary headaches
due to another medical condition
secondary headache examples (3)
- sinus headache
- brain tumor
- meningitis
migraine
moderate to severe headache interferes with normal functioning
how long do migraines last?
4-72 hours
two types of migraines
aura (25%)
without aura (75%)
aura
neurological symptoms that occur prior to and during a migraine headache; caused by cortical spreading depression
non rapid eye movement
not deep sleep, normal muscle tones, dec metabolism, HR,RR,BP
rapid eye movement
deep sleep and vivid dreams; inc in metabolism, low muscle tone, variations in VS
insomnia
difficulty falling asleep; constant awakening
the difference between primary insomnia and secondary insomnia
primary - unknown cause; 10-20%
secondary - stress; 80-90%
two types of sleep problems (insomnia types)
- onset insomnia (initiating sleep)
- maintenance insomnia (staying asleep)
Narcolepsy
uncontrollable excessive daytime sleepiness; altered REM/NREM
narcolepsy type 1
narcolepsy with cataplexy
cataplexy
loss of muscle control from strong emotions
narcolepsy part 2
narcolepsy without cataplexy
pathophysiology of narcolepsy
loss of orexin containing neurons
restless leg syndrome
desire to move limbs during rest
pathophysiology of restless leg syndrome
iron deficiency, poor circulation, dysfunction of dopaminergic neurotransmission
sleep apnea
repetitive upper airway, closure during sleep, decrease or stops in airflow leads to waking up
pathophysiology of sleep apnea
structure in jaw/neck or fatty deposits in neck
parasomnias
undesirable physical/behavioral phenomena occurs during sleep
NREM disorders of parasomnias
sleepwalking, sleep terrors, sleep talking, etc.
REM behavioral disorders
paralysis fails to occur during REM sleep, acting out in their dreams
circadian rhythms disorders
misalignment in sleep cycle
Guillain Barre Syndrome (GBS)
autoimmune disorder, attacks myelin around PNS neurons leading to schwann cell and neuronal damage
what is GBS triggered by?
infection or vaccine. it is typically reversible
symptoms of Guillain Barre Syndrome
-tingling sensation in extremities (paresthesia)
-difficulty with eye muscles, vision, swallowing, speaking, chewing
-pins and needles in hands/feet
-severe pain at night
Pathogenesis of GBS
molecular mimicry between offending agents and peripheral nerve gangliosides; leads to antiganglioside antibodies
Multiple Sclerosis
autoimmune, neurodegenerative disorder; attacks myelin surrounding CNS neurons leads to oligodendrocyte and neuronal damage
symptoms of MS are dependent
on location of demylenation
symptoms of MS in cerebellum
different in balance and coordination
symptoms of MS in optic nerve
loss of vision, eye pain, involuntary eye movements (nystagmus)
pathophysiology Outside In for MS
trigger activates T cell/B cell outside (PNS) and leads to infiltration of these cells into the CNS via dysfunctional BBB
pathophysiology Inside Out for MS
disturbance in a metabolic process in the brain, leading to release of inflammatory cytokines/chemokines which compromises the integrity of BBB allowing T and B cells in
Symptoms of MS occur based on
plaques
CIS
clinically isolated syndrome of MS; symptoms last 24 hours and may or may not be MS
RR
relapse remitting MS
PP
primary progressive MS
SP
secondary progressive MS
85% originally diagnosed with this type of MS
relapse remitting
Parkinson’s disease
movement disorder which occurs due to loss of dopamine producing neurons in the substantia nigra; lewy bodies present
non motor symptoms of Parkinsons
Inosmia , rapid eye movement disorder, dementia, altered ANS function and REM sleep disorder
pathophysiology of Parkinson’s
presence of Lewy bodies - abnormal aggregates of alpha synuclein protein in neurons - Lewy bodies in brain stem
loss of dopamine containing substantia nigra neurons lead to depigmentation in sub. nigra leads to motor symptoms
dementia
collection of symptoms including decline in memory, reasoning and communication skills
Alzheimer’s
build up of beta amyloid plaques and neurofibrillary tangles
vascular dementia
damage to cerebral vasculation from conditions like hypertension, smoking, etc.
lewy body
Abnormal aggregates of alpha-synuclein protein which form inside of neurons
initial symptoms of lewy bodies
REM, hallucinations, etc.
Frontotemporal Dementia (Pick’s Disease)
degeneration in frontal/ temporal lobes and abnormal tau accumulation
initial symptoms of Pick’s disease
changes in personality, difficulty to produce language
glutamate is
excitatory, tells the neuron to fire
GABA is
inhibitory, dampens the firing rate
Who brings information to the cell body? who takes information away?
dendrite bring
axons take away
Neurotransmitter synthesis enzymes
enzymes responsible for the synthesis of the NT
VG Na+ channel
responsible for depolarization in neuronal action potential
VG Ca2+ channel
activated by membrane depolarization, CA influx leads to NT release
Postsynaptic receptors
activation of these receptors leads to the physiological response of the NT
Degrading enzymes
responsible for degradation of NT, can be located intra/extracellularly
reuptake pump/transporter
transporters responsible for uptake of the NT from the synapse back into the presynaptic neuron
Presynaptic autoreceptors
activation of presynaptic autoreceptors decreases NT release; negative feedback
vesicular transporter
located presynaptically and responsible for uptake of NT into vesicles for storage
Pathophysiology of circadian rhythm disorders
Misalignment of light-dark cycle of sleep
Oligodendrocytes
Myelinating neuronal axons in CNS
Schwann cells are the myelinating cells of the
PNS
Myelin
Fatty substance that increases the rate of action potential; protective layer
Nodes of Ranvier
Spaces between myelin sheaths with high density of VG NA channels; allows action potential to travel quickly
GBS attacks what type of neurons leading to what type of damage?
PNS neurons; Schwann cell and neuronal damage
Pathogenesis of Acute Inflammatory Demyelinating Polyneuropathy
Because of T cell mediated cytokine storm; no detectable antibodies
Acute Motor Axonal Neuropathy and Acute Motor and Sensory Axonal Neuropathy are associated with
Traditional anti ganglioside antibodies
In MS what type of neurons are attacked?
CNS neurons
What is the immune response when T cells encounter myelin in MS?
What do B cells produce?
Production of pro inflammatory cytokines, tumor necrosis factor alpha, interferon gamma
B cells produce auto antibodies
In MS, regulatory cells may
Reduce the immune response leading to periods of remission
MS plaques in brain stem lead to
Difficulty swallowing, slurred speech
MS plaques in the cerebellum lead to
Difficulty with balance and coordination
MS plaques around the optic nerve lead to
Loss of vision, involuntary eye movements (nystagmus)
MS plaques along the motor pathways lead to
Tremor, muscle weakness, muscle spasm, paralysis
MS plaques in sensory pathways lead to
Paresthesia, loss of sensation
MS plaques in the cerebral cortex lead to
Cognitive impairment, fatigue
MS plaques on spinal nerves may result in
Urinary incontinence, sexual dysfunction and spasticity
Parkinson’s diseases may be ___ or ___
Familial or sporadic
Most of the medications used in PD
Enhance dopamine this neurotransmission but does NOT reduce or prevent loss of neurons
Essential criteria for diagnosis of PD
Bradykinesia with at rest tremor and rigidity
PD is characterized by
Lewy bodies in the brain stem
Alpha- synuclein
Endogenous protein found in presynaptic nerve terminals
Reduction in dopamine in what pathway leads to motor symptoms of PD?
Nigrostriatal pathway
Bradykinesia?
Dyskinesia/hyperkinesia?
Too little dopamine
Too much dopamine
Lewy body dementia
Build up of alpha synuclein in the cortex
changes in the brain can
occur long before symptoms start to show
dementia is caused by ___ and nerve cells become ____ and certain parts of the brain ____.
- physical brain diseases
- damaged and start to die
- starts to shrink
Amyloid plaques pathophysiology in AD
extracellular beta amyloid deposition leads to generation of senile plaques
Tau pathophysiology in AD
Tau becomes abnormally phosphorylated by kinases which leads to aggregation and structural dysfunction of neurons
Hyperphosphorylated tau
dissembles microtubules and damages the cytoskeleton and signal transduction processes of neurons
Other factors that play a role in AD (4)
neuroinflammation
cholinergic insufficiency
mitochondrial dysfunction
autophagy dysfunction
Alzheimers disease is a
neurodegenerative disorder
early onset AD
due to familial AD
due to mutations that lead to increased pathogenic amyloid beta
5% of cases
late onset AD
combination of genetic and environmental factors
95% of cases
genetic risk factor of Late onset AD
APOE4 gene
Cholinergic hypothesis of AD
loss of cholenerigc activity is associated with AD severity, enhancing cholinergic signaling preserves cognitive function (ex: inhibit AChE)
Glutamatergic hypothesis of AD
excess activation of NMDARs by glutamate leads to exitotoxicity and neuronal death in AD (block NMDARs to dec exitotoxicity)
Amyloid precursor protein
transmembrane protein that plays a role in neuronal growth and repair; cleaved by secreatases which leads to AD
Tau
intracellular protein that usually stabilizes neuronal microtubules
Preclinical AD
no symptoms but biomarker evidence, can be 20 years before presence
MCI due to AD
mild cognitive impairment; mild symptoms and biomarker
Dementia due to AD
impaired daily function and biomarker
examples of biomarkers (3)
decreased CSF AB42, increased CSF p-tau, decreased brain glucose metabolism
Diagnosis of AD is based on
clinical assesment
what is needed for a definitive diagnosis of AD
Histopathological analysis; done during autopsy
Image studies to support diagnosis of AD (3)
- MRI - hippocamal atrophy
- FDG-PET and SPET - reduced cerebral flow and metabolic changes
- Amyloid PET - beta amyloid plaque density
convulsion
sudden attack of involuntary muscular contractions/relaxtations
seizure
abnormal CNS electrical activity
epilepsy
a group of recurrent disorders of cerebral function characterized by both seizures and convulsions
electroencephalogram
plays a central role in diagnosis with seizure disorders; can show irregular activity in the brain that indicates seizures
causes of epilepsy (7)
genetic, vascular, severe head trauma, infections, tumor, drug abuse, unknown
greatest cause of epilepsy
UNKNOWN!
Partial seizures and 2 types
excessive electrical activity in one cerebral hemisphere
types: simple and complex
Simple partial
preservation of consiouness
complex partial
loss of awareness at seizure onset, originate in frontal or temporal lobes
generalized seizures
excessive electrical activity in both cerebral hemispheres; loss of consciousness is common
generalized seizures originate in the ___
thalamus and brainstem
tonic seizures
sudden stiffening of the body, arms and legs
clonic seizures
rhythmic jerking movements of the arms and legs without a tonic component
does a normal of EEG rule out a seizure? why?
it does not rule out epilepsy. it can only show wavelengths during the test and the abnormal brain waves only happen during a seizure
other techniques that can help diagnose epilepsy
MRI
epilepsy
two or more unprovoked seizures that can’t be explained by a medical condition
seizures are due to
an imbalance in excitation and inhibition in the brain
pathophysiology of epilepsy
neuronal networks are overreactive
can be enhanced excitatory (inc in glutamate)
can be reduced inhibitory ( dec in GABA)
can be enhancement of overall NT (inc in AP)
Brain injury
alterations in level of consciousness and in cognitive, motor or sensory function
focal brain injury
injury to one specific area
global brain injury
injury to entire brain or numerous areas of it
mechanisms of brain injury (4)
direct damage
ischemia/hypoxia
excitotoxicity
excessive intracranial pressure
excitotoxicity
due to glutamate buildup and excessive Ca2+ influx through NMDARs
Traumatic brain injury is the
leading cause of death and disability among people under than 24
primary injury of traumatic brain
damage caused by impact
secondary injury of traumatic brain
damage caused by subsequent brain swelling, infection or ischemia
concussion
mild type of TBI
persistent vegetative state
loss of all cognitive functions and awareness for at least one month
brain death
irreversible loss of function of the brain and brain stem
Psychological disorders
disturbances in mood, thoughts and behaviors
most psychiatric disorders have a
significant genetic component and environmental factors
schizophrenia
positive symptoms, negative symptoms and cognitive dysfunction
bipolar disorder
cyclic mood disorder characterized by episodes of mania and depression
major depressive disorder
mood disorder characterized by depressive episodes
anxiety disorders
excessive anxiety
ADHD
primarily a disorder of the prefrontal cortex; executive function and maintaining attention
pathophysiology of ADHD
dysregulation of dopaminergic and adrenergic systems
Schizophrenia
characterized by positive symptoms, negative symptoms and cognitive impairment
example of a positive symptom
hallucination
example of a negative symptom
reduced motivation
the most disabling disorder
schizophrenia
dopaminergic hypothesis
inc in dopaminergic activity in mesolimbic, decrease in mesocortical, imbalance leads to schizophrenia
mood disorders
affect a person’s emotional state
most common mood disorders
depression and bipolar disorder
Depression
at least one episode of depression (persistent sadness or loss of interest along with other symptoms)
monoamine hypothesis
normal amount of monoamine NT becomes reduced, depleted, or dysfunctional, depression occurs
HPA axis
hypothalamic pituitary axis; activated by stress
overreactive HPA
in states of chronic stress; associated with MDD and anxiety disorders
there is an association between elevated cortisol levels and
depression
spina bifida
most common NTD; one or more vertebrae fail to form a complete vertebral arch for enclosure of the spinal cord
Neuronal tube defects
stop in normal development of the brain and spinal cord during the first month of development
why is supplementation of folic acid important?
deficiency in B9 could increase risk for NTDs
when should folic acid supplementation begin?
before conception
spina bifida occulata
small gap in spine, no protrusion
meningocele
meninges protrude outward
myelomeningocele
spinal cord and meninges protrude outward leading to spinal cord damage
autism
bio-neurological developmental disability, appears before the age of 3
individuals with autism also suffer from
numerous comorbid medical conditions
