Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PBL Notes > PBL 4- Epilepsy > Flashcards

PBL 4- Epilepsy Flashcards

1
Q

What makes up myofilaments

A 
Myofilaments:
	- Contain protein 
		○ Actin
		○ Tropomyosin
		○ Troponin
	- Thick Filaments
Myosin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What happens at the neuromuscular junction?

A
  • Ach released at NMJ
    • AP generation in muscle cell
    • Ca influx
    • Myosin-actin interaction
      Contraction occurs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the A-motorneuron?
Where are they located?
What is the structure?

A
  • Large diameter myelinated
    • Final neurons located in the ventral horn of the spinal cord
    • Their axons form the ventral root
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is a motor unit?

A
  • The smallest functional unit for movement
    • Consists from:
      ○ Single a-motor neuron
      ○ Its axon
      Plus all the muscle fibres innervated by the neuron
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is a motoneuron pool?

A

A group of neurons (a column) that innervate one muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is The neuromuscular junction

A
  • The synapse between the motoneuron axon terminal and the muscle fibre
    The arrival of the action potential along the neuron to the terminal causes release of a neurotransmitter
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What degrades/ rate limits the Ach in the NMJ?

A
  • Cholinesterase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What kind of receptors bind Ach in the NMJ?

A

Nicotinic ion channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What allows the muscle to be a “smooth” contraction?

A
  • Temporal summation of action potential leads to tetanus

Ceases when stimulation ceases or when fatigue begins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Drugs that effect the neuromuscular junction

A 
- Curare 
		○ ACH receptor blocker 
		○ Results in Paralysis of the muscle
	- Physotigmine 
		○ cholinesterase inhibitor
		○ potentiates effects of Ach
		○ Muscle spasm at overdose
	- Organophosphates
		○ Cholinesterase inhibitor
	- Botox
		○ Ach Release Blocker
Results in paralysis of muscle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which Motor Neurone innervates a muscle spindle/ intrafusal fibres?

A
  • Gamma motor neuron

Intrafusal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which motor neuron innervates an extrafusal fibre

A

Alpha motor neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What does a Golgi tendon do?

A

Detects tension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does a muscle spindle do?

A

Detects changes in muscle length

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is a reflex?

A
  • Responses to sensory stimuli without participation or contribution of consciousness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the key features of a motor reflex?

A
  • They are elementary acts of behaviour
    • Stimulation of a given output produces determined and predicted output
    • Performed without conscious control
    • In a reflex the afferent input strictly determines output- there is NO contribution of will.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Where is the primary motor cortex located?

A
  • M1
    • Area 4
      Pre central gyrus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are Betz cells?

A
  • Pyramidal cell neurons in the primary motor cortex
    • Send axons down the corticospinal tracts to the anterior horn cells of the spinal cord
    • Lie in the deep area of the cortex
      Responsible for initiating voluntary and conscious movement.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Damage to the capsula interna would result in what clinical signs?

A

Paralysis and sensory loss on the CONTRALATERAL side

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why does the membrane potential occur?

A

Separation of oppositely charged ions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is responsible for the membrane potential?

A
  • Inside is negative compared to outside
    • Determined by the concentration gradient of Potassium
      Loss of K results in a negative charge
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What ensures that the membrane potential remains constant?

A

Active transport pumps (Na/K ATPase) ensure that the electrochemical equilibrium does not occur

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is a nerve terminal?

A

A secretory machine that is dedicated to rapid rounds of NT release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is hyperpolarisation?

A

A refractory period where no new action potential can be granted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What ion causes the depolarisation phase?

A

Na influx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What ion causes the repolarisation phase?

A

K efflux

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What causes hyperpolarisation?

A
  • Inhibitory post synaptic potential
    • Prevents excitation or terminates action potential
    • Restores voltage to original value
    • Cell becomes more negative inside
      Through influx of CL- and Efflux of K+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What causes Depolarisation?

A
  • Excitatory post synaptic potential
    • Cell becomes less negative inside
    • Influx of NA and Ca
      No potassium leaving the cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Different broad types of Ion Channel types

A
  • Voltage-gated
    • Ligand-gated (extracellular ligand)
    • Ligand-gated (intracellular)
      Mechanically gated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Voltage Gated ion channels
What are they made from?
How are they gated?
What type of signal do they give?

A
  • Pore forming proteins
    • Gated: opening is voltage dependent
      ○ Flow is according to pre-existing electrochemical gradients
    • High flow selectivity
    • High throughput
      ○ Thousands of ions flow per second
      ○ Large and brief electrical signal
    • High variety
      Complex range of signals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Domains of voltage gated Na, Ca and K

A
  • S4 family = the pore forming subunit
    • Built on a motif of 6 TM (S1-S6) segments
    • S4 = the Voltage sensor
    • Pore Loop domain = S5-S6
      Forms complex with auxiliary sub units
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the purpose of the auxillary sub units of a voltage channel?

A
  • They are associated with the channel

- Modulate gating, kinetics, intracellular trafficking, current amplitude

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How are voltage gated channels modulated?

A
  • Voltage
    ○ Activation and inactivation kinetics depending on cell type and channel sub type
    • Activation gate
      ○ Responds to voltage changes
    • Inactivation Gate
      ○ Na channels - close the gate
    • Auxilary subunits
    • Protein phosphorylation/dephosphorylation
      ○ Action of protein kinases and phosphatases
      ○ Na phosphorylation slows its inactivation
    • Binding of toxins and drugs
      Ion channel subtype specificity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Voltage gated K channels

A
  • Involved in the REPOLARISATION phase
    • Terminates action potential
      Rate of closing affects excitability ( ability to rapidly fire)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Therapeutic targets for K channels?

A
  • When action potential firing is decreased in CNS depression
    ○ K channel inhbitors
    • When pathological hyperexcitability
      K channel activators
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Voltage Gated Calcium Channels
How is it classified?
What role does it have
how is it modulated?

A
  • Classification is according to the Alpha 1 subtype
    • Critical role in NT release, synaptic plasticity and PAIN
      Complex modulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Therapeutic targets for N-type calcium channels

A
  • Associated with Pain
    • Opiates
      Derivatives of conotoxins= analgesics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q 
Voltage Gated Na channels
Describe the gates
How is it regulated?
What role does it have?
How does it appear in the different phases of the AP?
A
  • Has 2 gates
    • Activation gate
    • H = Inactivation gate
    • Regulated by Phosphorylation
    • Opening is responsible for the rising phase of the action potential
    • In the repolarisation phase the activation gate is open but the inactivation gate is closed
    • Resting = activation is closed and inactivation is open
      Depolarisation phase = both open
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Clinical significance of Na channels

A
  • Important in transduction of noxious signals -> pain pathways
    • Local anaesthetics like lidocaine block Na conductance by binding to the inner portion of the Na channel
    • Targets for many epileptic drugs
      Targets for many toxins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Tetrodotoxins

A
  • TTX- producing bacteria
    • Prevent the Na flow
      ○ Bind to the outside of pore independent of voltage status- alpha subunit
      Most Na channels in CNS and PNS are TTX sensitive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Voltage gated Chloride channels
General structure
what role does it have?

A
  • 9 proteins- glial and neuronal
    • Has two pores
    • Channels are arranged as dimers
    • Separate (fast) or common gating - opening/closing of 2 pores
      Alterations associated with juvenile epileptic syndrome, gliomas.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Ionotropic receptors

A
  • Not a transporter
    • If no ligand they are closed
    • Multimeric protein
      Opening typically requires binding of more than one neurotransmitter molecule
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What are the types of Ionotropic Neuro transmitters

A 
- Excitatory 
		○ Nicotinic (Ach, Da, NE)
		○ 5HT3 (5HT)
		○ AMPA, NMDA (Glutamate)
	- Inhibitory
GABA a (GABA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

GABA a Receptors
What type of receptors?
role?

A
  • Ligand gated ion channels
    • Responsible for hyperpolarisation (CL influx, K efflux = decreased depolarisation)
      Terminates or prevents initiation of action potential
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Cation-selective ligand gated ion channels

What type of receptors?

A
  • Neuronal ACH receptors
    • Glutamate NMDA (NA and Ca)
      Glutamate AMPA (Na)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What happens in Seizure initiation?

A
  • Burst of action potentials called a paroxysmal depolarising shift
    Abnormal and excessive synchronisation of neighbouring populations of cortical cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How is a Seizure propagated?

How is it mediated?

A
  • Ie partial seizure that spreads
    • Activation of nearby neurons
    • Loss of surrounding Inhibition
    • Aberrant excitability associated with epileptic discharge mediated by voltage gated and ligand gated ion channels

May also be a result of genetic defects in channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What are the Key features of seizure generation

A
  • TOO MUCH EXCITATION
    ○ Leads to sustained, overt depolarisation and excessive discharge
    ○ Mediated by ions - inward NA and Ca currents
    ○ Mediated by NT - Glutamate
    • TOO LITTLE INHIBITION
      ○ Leads to defects in hyperpolarisation
      ○ Mediated by ions : inward CL and outward K
      Mediated by NT = glutamate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is the paroxysmal depolarisation shift?

A
  • Characteristic sustained depolarisation with repetitive spiking (burst firing)
    Occurs synchronously in a large group of neurons
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Role of channels in epilepsy

A

Voltage gated NA and CA channels are major AED targets
○ Inhibitors of these inhibit high frequency repetitive spiking

GABA a receptors = second major AED targets
○ Drugs that ENHANCE INHIBITION are used as anticonvulsants
○ Prevent AP propagation and seizure spread
○ Phenobarbitol
○ Inhibitors of GABA degradation or reuptake

Others
○ Antagonists of NMDA receptors- to prevent excitation
○ Activators of voltage gated K channels
Blockers are powerful convulsants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Describe general Brain metabolism/ energy requirements

A
  • The brain depends on a large and stable blood supply
    • It has no effective way to store oxygen or energy
    • High metabolic demand is met by a high blood flow to deliver energy substrates and oxygen
      Local blood flow rates vary depending on neuronal activity
52
Q

What is the main source of ATP for neurons?

A

Mitochondrial oxidative Phosphorylation

53
Q

Why is ATP so important in the brain?

A
  • Maintains Ion gradients
    • If you lose ATP there is an inhibition of the Na, K ATPase pump
    • Destruction of ion gradients
      Results in energy failure and neuronal death
54
Q

What is Phosphocreatine?

A
  • Can be used transiently to regenerate ATP
    • Used under ANAEROBIC conditions
    • Used in skeletal muscle and brain
    • Used when:
      ○ Intense muscular effort or neuronal demand
      A decrease in phosphocreatine is seen prior to a decrease in ATP in anaerobic conditions because brain would utilise pcr as needed
55
Q

What is The blood brain barrier:

A
  • Specialised system of capillary endothelial cells
    • Enclosed by end feet of astrocytic cells
    • Separates circulating blood and CSF
    • Is a physical and metabolic barrier
    • Protects brain from harmful substances while supplying required nutrients
    • Tight junctions disrputed in many CNS pathologies
  • Provides the rate limiting factor in permeation of drugs
56
Q

Molecular trafficking through BBB

ie how to things go through the BBB?

A
  • Paracellular pathway
    ○ Through the tight junctions
    ○ Small, water soluble
    • Transcellular
      ○ Lipid soluble
      ○ Usual pathway for drugs
    • Transport proteins
      ○ Glucose, amino acids, nucleotides
      ○ Also has efflux transporters
      Cyclosporin a
57
Q 
Glucose and the brain
Use:
Storage:
Transport:
How can it go wrong?
A

Use:

- In the fed state glucose is the main fuel for the brain
- Brain completely oxidises glucose to CO2 and water
- Required for normal brain function and development

Storage:

- No storage of glycogen in neurons
- Some glycogen stores in astrocytes

Glucose transport:

- facilitated diffusion
- GLUT 1 transporter = BBB endothelial cells and astrocytes
- GLUT 3 transporter = Neuronal specific 
- High affinity and high capacity glucose transport (facilitated diffusion)

How it can go wrong?
- GLUT1 deficiency syndrome- defective glucose transport across BBB- low glucose in CSF in presence of normal glycaemia
○ Infantile seizures and developmental delay
Abnormal expression and/or activity of GLUT1 in chronic epilepsy = decreased glucose uptake

58
Q

What is GLUT1?

A

Glucose transporter in BBB endothelial cells and astrocytes

59
Q

What is GLUT 3?

A

Neuronal specific glucose transporter

60
Q

What is the glucose transporter for BBB endothelial cells?

A

GLUT1

61
Q

What is the neuronal specific glucose transporter?

A

GLUT 3

62
Q

When are alternative brain fuels used?

A
  • When energy demands exceed glucose supply brain can utilise lactate and ketone bodies
    • During:
      ○ Development
      ○ Hypoglycaemia (Ketones)
      ○ Starvation
      Situations of intense neural activity
63
Q 
Ketone Bodies
Where are they produced?
How are they utilised?
What is their importance
How can this be used clinically?
A

Produced:
- In the liver in response to starvation

Utilisation:
- Up regulation of transport across BBB during starvation

Importance:
- Development
Uses:
A ketogenic diet can be an effective treatment of epileptic seizures in GLUT 1 deficiency syndrome- will use ketones rather than glucose

64
Q

Oxidative phosphorylation
Is oxygen required?
What is the process?

A

Oxygen:
- Necessary for this process
Process:
- Glucose metabolised to pyruvate via glycolysis
- Pyruvate is then completely oxidised in the mitochondria to CO2
Produces a lot of ATP

65
Q

Anaerobic glycolysis
Is oxygen required?
What is the process?

A

Oxygen :
- Used when oxygen is limiting

Process:
Cells redirect the pyruvate generated by glycolysis away from mitochondrial oxidative phosphorylation by generating lactate

66
Q

What is Aerobic Glycolysis

A
  • Conversion of glycose to lactate when oxygen is PRESENT
    • Much less efficient than oxidative phosphorylation for generating ATP
      Process can exist in tumours - Warburg effect
67
Q 
Lactate
What are its uses?
When does it increase in its use?
What is the role of the neuron?
sources of lactate?
A 
Uses:
	- Underlies the energetics of diverse brain activities
		○ Long term memory function
		○ Sensory processing 
		○ Pathophysiological conditions
	- Increases in response to:
		○ Hypoglycaemia
		○ Ischaemic events 
		○ Stress
	- Could be present in the resting brain however research isnt sure

Role of neurons:
- Can transport and oxidise lactate

Sources of lactate when brain activity is increased:
- Net influx of lactate from blood to brain - via lactate transporters
- Increase in local aerobic glycolysis (increased neuronal/astrocyte glucose uptake)
- Astrocyte- neuron lactate shuttle hypothesis
○ Lactate generated from astrocyte glycogen breakdown
Transported into neurons for use

68
Q

What is the response to falling plasma glucose?

A
  • Prolonged and severe hypoglycaemia is rare in humans

The brain is very tolerant to changes in glucose

69
Q

What happens in the Early stages of hypoglycaemic coma
What does the EEG show?
What changes do you see in oxygen, energy, phosphocreatine and ATP levels?

A
  • Normal oxygen and energy levels
    • Oxygen consumption continues
    • Eeg shows slow waves and polyspikes
    • Levels of phosphocreatine and ATP remain NORMAL unless there is respiratory depression
70
Q

What happens in Prolonged and severe Hypoglycaemia?

A
  • Some loss of ATP = approximately 25-30% of control levels
    • There is not a complete energy loss
    • loss of ATP correlates with onset of flat (isoelectric) EEG
    • Neuronal damage results from oxidative stress
    • Neuronal death takes several hours
      Mechanisms for damage/death:
      Increased neuronal release of glutamate leads to oxidative stress
71
Q

What is Oxidative stress:
When does it occur?
what does it lead to?

A
  • Results from imbalance between levels of reactive oxygen species ROS and antioxidants
    • ROS such as peroxides and radicals are derived form inherent aerobic metabolism of oxygen
    • Under normal circumstances cells are able to balance the production of oxidants and antioxidants resulting in the redox equilibrium
    • Oxidative stress occurs:
      ○ Cells are exposed to excess levels of ROS and/or
      ○ As a result of antioxidant depletion
    • Leads to:
      ○ Mitochondrial damage
      ○ DNA damage
      Ultimately leading to energy failure and death
72
Q 
Hypoxia
Causes:
Effects:
Mechanisms to avoid metabolic failure?
What is a clinical risk of treatment?
A

Causes:
- Systemic/local blood circulation defects eg Stroke

Effects:
- Not tolerated for long periods due to insufficient energy supply to brain
- Activation of short and long term adaptive mechanism
○ Activated by oxygen sensing systems
○ Activation depends on duration and severity of deprivation
○ Does this to avoid metabolic failure and risk of oxidation toxicity

Mechanisms to avoid metabolic failure:
○ Increase in local blood supply (autoregulation of cerebral blood flow, increases cardiac output, vasodilation)
○ Shut down of non-essential energy consuming mechanisms
○ Changes in gene transcription and protein synthesis to stimulate production of RBC and angiogenesis

Risk:
Excessive reoxygenation = risk of cell injury by increased inflammation and oxidative stress

73
Q

How does energy failure occur in hypoxia/ischaemia?

A
  • Lack of oxygen
    • Utilisation of Phosphocreatine
    • Rapid ATP exhaustion
    • Blocking of ATPase (NA/K)
    • Collapse of ion gradients
      Rapid and large depolarisation
74
Q

Events during brain ischaemia

A
  • ATP failure
    • Collapse of ion gradients
    • Massive depolarisation due to influx of NA and CA and efflux of K
    • Increased Glutamate released
    • NMDA receptor activation
    • Increased CA influx
      Increased acidification (lactic acidosis)
75
Q

Explain the link between Ischaemia and lactic acidosis

A
  • The Ischaemic brain has no O2 so uses anaerobic glycolysis to meet the brains energy requirements
    • This leads to production of lactate
    • Excessive accumulation of lactate aggravates brain damage during ischaemia due to enhanced lactic acidosis
    • The intensity will depend on glucose sotres
      There is NO lactic acidosis in hypoglycaemia- THERE IS NO GLUCOSE PRECURSOR TO MAKE LACTATE
76
Q

What are the secondary mechanisms of ischaemic cell death?

A
  • intracellular calcium overload
    ○ Due to increased calcium influx from increased glutamate release
    ○ Oxidative and metabolic stress leading to cell death
    ○ This occurs via mitochondrial failure, disruption of cell membranes and changes in gene transcription
    • Inflammatory reactions
      ○ Microglia
    • Blood Vessel leakage
    • Brain oedema
      BBB breakdown
77
Q

What is the time course of hypoxic-ischaemic brain injury?

A

Immediate: 2-10 minutes
- Necrotic cell death
○ Due to Na overload and increased glutamate

Delayed: 6-72 hours
	- Delayed necrotic and apoptotic cell death
		○ Ca overload and oxidative stress
		○ Mitochondrial dysfunciton 
		○ Inflammation 
BBB failure
78
Q

What brain sites are most vulnerable to cerebral ischaemia?

A
  • Hippocampal CA1

All middle laminae of the cortex

79
Q

Describe what happens to the brain metabolism during the ictal phase of a seizure:

A
  • Increased metabolic rate (250%) = hypermetabolic
    • Increased cerebral blood flow to supply glucose and nutrients
    • Very small perturbation of tissue energy state and ion homeostasis (ATP remains stbale - 99%)
      Increased lactate production during and as a result of a seizure (due to increased demands for glucose)
80
Q

Describe the changes in metabolism during the INTERICTAL PERIODS of a seizure

A
  • DECREASED requirement - lower than normal glucose uptake and blood flow
    • Altered GLUT 1 expression at BBB endothelium
      Decreased glucose uptake within epileptic areas/foci
81
Q

What is 2DG?

A
  • Assessment of brain glucose metabolism - indirect measure of neural activity
    • It competes with glucose for entry into cell and accumulates
    • It cannot be catabolised
      PET scan with flurescent derivative ( 18F)FDG can identify low metabolism seizure sites in interictal period
82
Q

What are the cellular events in response to an epileptic insult?

A

Repeated and prolonged seizures can lead to irreversible damage and cell loss and reorganisation of synaptic networks

First minute to hours after status epilepticus insult:
- Cell loss
- Hippocampal sclerosis
○ Excessive activation of excitatory glutamate receptors which results in glutamate excitotoxicity
○ Oxidative stress leads to damage of mossy cells and loss of GABAergic inhibition
- Astrocyte proliferation and dysfunction as a result of neuronal damage
- Inflammation and BBB failure
- Moderate lactate acidosis compared to ischaemia

Several hours to months  after seizure insult
	- Disease progression
	- Long term damage
	- Chronic increase in calcium
		○ Changes to gene expression initiating synaptic remodeling events 
		○ Eg neurogenesis
	- Acquired channel dysfunction 
BBB dysfunction
83
Q

The links between BBB function and seizures?

A
  • Seizures can cause BBB failure leading to BBB leakage
    • BBB failure can lead to seizures
      ○ Acquired BBB defects such as head trauma and brain tumours
      ○ Multiple drug resistance can be due to defects in transporters in the BBB
      ○ Metabolic BBB defects such as GLUT1 deficiency syndrome
      Systemic and immune triggers.
84
Q

General function of areas of the brain

Cerebrum:

A
  • Conscious thought processes
    • Intellectual functions
    • Memory storage and processing
      Conscious and subconscious regulation of skeletal muscle contractions
85
Q

General function of areas of the brain

Thalamus:

A

Relay and processing centres for sensory information

86
Q

General function of areas of the brain

Hypothalamus:

A
  • Center controlling emotions
    • Autonomic functions
      Hormone production
87
Q

General function of areas of the brain

Midbrain:

A
  • Processing of visual and auditory data
    • Generation of reflexive somatic motor responses
    • Maintenance of consciousness
88
Q

General function of areas of the brain

Pons:

A
  • Relays sensory information to cerebrum and thalamus

Subconscious somatic and visceral motor center

89
Q

General function of areas of the brain

Medulla oblongata:

A
  • Relays sensory information to thalamus and to other portions of the brain stem
    Autonomic centers for regulation of visceral function (cardiovascular, respiratory and digestive system activities)
90
Q

General function of areas of the brain

Cerebellum:

A
  • Coordinates complex somatic motor patterns

Adjusts output of other somatic motor centers in brain and spinal cord

91
Q

Which brain areas are responsible for attention?

A
  • Dorsolateral prefrontal cortex
    • Ventrolateral prefrontal cortex
    • Parietal cortex
    • Dorsal anterior midcingulate cortex
    • Striatum: caudate and putamen
    • Cerebellum
92
Q

If a patient showed Hemineglect- which lobe of the brain is effected?
Which side is most likely?

A
  • Parietal association cortex

In particular the right hemisphere

93
Q

What would deficits in the orbitofrontal cortex present as?

A
  • Disinhibition
    • Altered personality
    • Lack of empathy
    • Socially inappropriate behaviour
    • Reactive aggression
      Impaired “mind theory”
94
Q

What would deficits in the Dorsolateral prefrontal cortex present as?

A
  • Reduced attentional control
    • Perseveration
    • Impaired “executive” functions
      Working memory , sequencing, planning, creativity, reasoning
95
Q

What would deficits in the Medial prefrontal cortex present as?

A
  • Decreased motivation
    • Apathy
    • Akinesia
    • Impaired detection of mismatches or errors
96
Q

What is consciousness?

A
  • State of awareness of self and the environment (space/time)
    • Being able to orientate and respond to new stimuli appropriately
    • Arousal and wakefullness
      ○ Depends on the functioning of cerebral hemispheres and the reticular activating system of the brainstem
    • Content and cognition: emotions
      ○ Depends on a functioning cerebral cortex
      ○ Confusion, delirium, stupor
    • Unconsciousness is a lack of awareness/responsiveness
    • Narrow meaning of consciousness = being awake
97
Q

What is an EEG?
Minimal amount of electrodes?
Where does it get contributions from?

A
  • Recording of electrical signals from the scalp
    • Minimal electrodes is usually 18
    • Waves come from synchronous contribution from a very large number of neurons
    • Contributions from both post synaptic potentials (excitatory and inhibitory) and action potentials
    • Cannot record EEG from a small amount or a single neuron
98
Q

Types of brain waves from an EEG:

A
  • Delta wave
    ○ Slow wave sleep
    ○ Coma
    ○ < 4hz
    • Theta
      ○ Drowsiness
      ○ 4-7 hz
    • Alpha
      ○ Relaxed wakefulness with CLOSED eyes
      ○ 8-15 hz
    • Beta
      ○ Active wakefulness
      ○ 16-30 hz
    • Gamma
      ○ Usually Artefact by muscular activity
      ○ 30-100 Hz
99
Q

What describe the waves seen in Slow wave sleep

A
  • High amplitude and low frequency
    • Synchronised EEG
      Delta waves
100
Q

Describe the waves seen in wakefulness

A
  • High frequency and low amplitude
    • Desynchronised EEG
      Beta waves
101
Q

What brain waves would you see if you were awake with closed eyes?

A

Alpha waves

102
Q

In Slow wave sleep- how to thalamic neurons fire?

A
  • They fire in bursts

Frequency is the same as delta waves

103
Q

In awake and REM sleep how do thalamic neurons fire?

A
  • Neurons fire single spikes in alpha frequency

Excitatory influences are then transmitted to cortex via thalamo-cortical projections

104
Q

Slow cortical waves are of what origin?

A

Thalamic

105
Q

What is the difference between EEG and fMRI

A

EEG:

- based on direct measurements of electrical activity of electrical activity of the brain 
- Excellent temporal resolution
- Poor spatial resolution

fMRI:

- Indirect measure- based on consequences of metabolic activation
- Poor temporal resolution (few seconds to mins)
- Good and improving spatial resolution
106
Q

REM Sleep:

What are EEG waves like?

A
  • Rapid eye movement
  • EEG waves are similar to wakefulness
  • Neurons fire single spikes in alpha frequency
107
Q

What is the Lateral Reticular formation?

What is another name for it?

A
  • Parvocellular

- Reflex connection to local cranial nerve nuclei

108
Q

What is the medial Reticular formation?

What is another name for it?

A
  • Magnocellular
    • Neurons make long ascending and descending axons
    • Involved in control of:
      ○ Movement
      ○ Posture
      ○ Pain
      ○ Autonomic function
      ○ Arousal
109
Q 
Noradrenergic neurons (In relation to arousal)
Where are they located?
Where do they project to?
What is the function?
A

Location:

- Locus coeruleus
- Ie bilaterally In the pons

Project to:

- The spinal cord to modulate autonomic reflexes and pain
- To cerebrum: for vigilance and responsiveness to unexpected environmental stimuli and mood
110
Q 
Serotonergic neurons (In relation to arousal)
Where are they located?
Where do they project to?
What is the function?
A

Located in:

- Raphe Nuclei 
- Midline along the brain stem

Project to:

- The spinal cord: modulation of AP, HR and Body temp
- The Hypothalamus: modulation of AP, HR and Body temp
- The Cerebrum: Mood and sleep/wake cycle
111
Q

Cholinergic neurons (In relation to arousal)
Where are they located?
What is the function?
When are Ach levels high and low?

A

Located:

- Pons and Midbrain 
- Pontomesencephalotegmental complex 
- Basal nuclei

Function:
- Influence cortical arousal during waking states and dreaming (REM)

Ach Levels:

- High during wake and REM sleep 
- Low during Slow wave sleep
112
Q

Histaminergic neurons (In relation to arousal)
Where are they located?
What is the function?
What effect to antihistamines have?

A

Located:
- Tuberal mamillary nucleus

Function:
- To help maintain arousal in forebrain

Antihistamines:
- Cause drowsiness if they cross the BBB

113
Q

Orexin/Hypocretin neurons (In relation to arousal)
What is orexin?
What is the function?
What does a deficit cause?

A

It is an excitatory Neuropeptide

Function:

- It provokes wakefulness
- Increaes thermogenesis 
- Increases appetite

Deficit:
- Causes Narcolepsy

114
Q

Which brain structure modulates sleep?
Where is this located?
What are the functions?
Where does it project to and what role does this have?

A

The Suprachiasmatic Nucleus
- Located in the rostral part of the hypothalamus

Functions:

- Brains biological clock
- Modulate via Retino-hypothalmic tracts 
- Output controls sleep onset and durations as well as associated bodily changes

Projects to:

Forebrain

- Attention
- Emotions
- Psychomotor performance

Pineal Gland

- Melatonin
- Suppressed by light

Hypothalmaus

- Hormonal control - TH, GH, Cortisol
- Metabolism
- Orexin

Brainstem

- Sleep/arousal state
- AP, HR, respiration
115
Q

What does Melatonin do?

A
  • Involved in light-induced entrainment of sleep cycle

- Secretion suppressed by light

116
Q

What is Orexin?
Where is it produced?
What does it do?

A
  • Neuropeptides
    • Produced by dorsal hypothalamus
    • Control appetite and arousal
    • Works as a neurotransmitter
117
Q

What cell groups are involved in the Ascending Arousal system?
What are the two main cholinergic pathways?
What is the end result?

A
  • Monoaminergic cell groups involved:
    ○ Noradrenaline, serotonin
    • Cholinergic inputs from pedunculopontine and laterodorsal tegmental nuclei

Two main cholinergic pathways:

- To the intralaminar nuclei of the thalamus - this then projects widely to the cortex
- To the lateral hypothalamic area to join with hypothalamic and basal forebrain cholinergic projections to cortex

Results in: massive diffuse cholinergic innervation of cortex

118
Q

What is the inhibitory Surround?

What is the importance of this?

A
  • When excitatory pyramidal neurons send projections to proximal neurons they also activate interneurons adjacent to them
    • The interneurons are GABAeric and send inhibitory projections to surrounding neurons
    • This creates an inhibitory surround
    • The inhibitory surround prevents synchronisation of adjacent neurons
    • This process is abnormal in epilepsy allowing synchronous firing of neurons
119
Q

What are the characteristics of a partial seizure?

A

• Occur in a limited part of the cerebral hemisphere
• Preceded by an aura
• The part of the brain that is involve will determine the symptoms
○ Ie sensory cortex will produce sensory symptoms
○ Motor cortex will cause twitching or stiffening in the opposite side
○ Temporal lobe will cause: hallucinations of smell, taste or sound, dejavu or flashbacks, fear, nausea
• Simple = remains conscious
• Complex = consciousness is impaired- ability to respond or remember the event
○ Usually display automatisms such as lip smacking
○ Usually begin in the temporal lobe however can arise from anywhere
• Can spread to becomes secondarily generalised

120
Q

What are the characteristics of a generalised seizure?

A

• Involved both sides of the brain from the beginning
• Consciousness is impaired immediately
• No recollections of the seizures
• Can begin as partial seizures that spread
• Subtypes
○ Tonic-clonic
○ Absences
○ Tonic
○ Myoclonic
○ Atonic

121
Q

What are the characteristics of a tonic-clonic seizure?

A
  • Lasts from a few seconds to 3-4 minutes
    • Often the person bites or swallows his or her tongue and may have difficulty breathing- sometimes to the extent that cyanosis occurs
    • Also signals transmitted from the brain to the viscera frequently cause urination and defecation
    • Post seizure depression of the entire nervous system
    ○ Stupor for many minutes after the seizure attack remains severely fatigued asleep for hours thereafter
    • Initiation of a tonic-clonic seizure
    □ Majority are idiopathic
    □ Many have a hereditary predisposition to epilepsy (1 in 50-100)
    □ Factors can increase the excitability of the abnormal epileptogenic circuitry enough to precipitate attacks
    ® Emotional stimuli
    ® Alkalosis caused by over breathing
    ® Drugs
    ® Fever
    ® Loud noises or flashing lights
    □ Traumatic lesions in the brain cause excess excitability of local brain areas
122
Q

What are the characteristics of absence seizures?

A
  • Begin in childhood
    • Last less than 10 seconds
    • Sudden stare and loss of facial expression
    • Possible rolling of eye upwards
    • Rhythmic blinking
    • Can be provoked by hyperventilation
    • Seizure usually involves much or most of the thalamo-cortical activating system of the brain
123
Q

What are the characteristics of Tonic Seizures?

A
  • Brief generalised stiffening
    • Last only seconds
    • Often occur in sleep
    • Common in those with intellectual disabilities
    • Causes “drop attacks”
124
Q

What are the characteristics of tonic seizures?

A
  • Sudden loss of tone
    • If sitting will cause “head nod”
    • If standing will fall
125
Q

What are the characteristics of myoclonic seizures?

A

• Appear like a sudden startle
• Brief (1 second or less) muscle contraction.
• Symptoms may occur in individual muscle or generalise to all muscle groups of the body
○ The latter can result in falling
• Associated with systemic diseases such as uraemia, hepatic failure, hereditary degenerative conditions
• Associated with mad cow disease

PBL Notes (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions