Neurology Flashcards
What are the two parts of the PNS?
Somatic PNS
Autonomic Nervous System
What is controlled by the somatic PNS?
Motor and sensory function for the body wall
What is controlled by the autonomic nervous system?
Regulates function of the viscera: internal organs, smooth muscle, pupils, sweating, blood vessels, bladder, intestine, glands and heart contraction rate
What are the three parts of the autonomic nervous system?
Sympathetic
Parasympathetic
Enteric
What direction do afferent axons send information?
Towards the brain and spinal cord from the PNS
What direction do efferent axons send information?
From the brain and spinal cord to the periphery
What are interneurones?
CNS neurons that synapse with other CNS neurons within the brain or spinal cord
What is the structure of the cerebral cortex?
Two hemispheres made up to Frontal lobe, Temporal lobe, Parietal lobe and Occipital lobe
In general, each received sensory information from and controls movement on opposite side of the body
What is controlled by the cerebellum?
Coordinates movement
Involved in learning motor skills
What is the main function of the brain stem?
Densely packed fibres. Controls vital functions (e.g. consciousness, breathing).
Cranial nerves provide sensory and motor innervation to the head.
Ascending and descending pathways connect the spinal cord with the forebrain
Damage here is serious, can be fatal
The dorsal and ventral roots that emerge from the spinal cord are part of what nervous system?
PNS
Give an example of an unmyelinated neuron
Nociceptors (pain)
What is the structure of a spinal nerve?
Contains both afferent and efferent axons bundled into fascicles surrounded by perineurium. The whole nerve is in a tough epineurium capsule
Axons in which nerves are able to regenerate after injury?
In peripheral nerves
What is found in white and grey matter?
Neuronal cell bodies are in grey matter
White matter comprises ascending and descending axon tracts to and from the brain
For a reflex response what inputs and outputs are required?
Somatic sensory inputs to the spinal cord
Interneurons and motor outputs from the spinal cord
What inputs and outputs are required for conscious registering and voluntary movement?
Sensory inputs activate sensory neurons in the spinal cord, grey matter transmits action potential upward to the sensory cortex of the brain.
Neurons in the motor cortex of the brain extend axons downward to synapse with the spinal motor neurons and transmit action potentials for voluntary movement
In the white matter of the spinal cord are the sensory and motor axons ascending or descending?
Sensory axon tracts: Ascending to the brain
Motor axon tracts: Descending to spinal cord
A 72 year-old patient has lost voluntary movement and sensation in his left arm, but the muscles still show reflex activity. His right arm and both legs function normally. Where would this injury occur in the nervous system?
Injury must be in the right hemisphere containing both motor and sensory neurons/axons- but only for the arm.
No peripheral nerve injury as reflex activity is intact.
Not spinal cord as only one arm affected and legs are fine
As 72 years old could be a stroke
A 19 year old patient has lost voluntary movement and sensation in her left arm. The muscles do not show reflex activity. Her right arm and both legs function normally. Where would this injury occur in the nervous system?
Likely to be a peripheral nerve injury to the left arm/shoulder since there is no reflex activity. Unlikely to be spinal cord as right arm is fine.
A 49 year-old patient has lost voluntary movement and sensation in his left arm and leg but the muscles still show reflex activity. His right arm and leg function normally. Where would this injury occur in the nervous system?
Injury not peripheral as reflex activity intact, plus both arm and leg affected.
Unlikely to be spinal cord as only one side affected
Injury likely to be in the right brain sensorimotor cortex as only left limbs affected, but spread across regions for both arm and leg
Possibly brain tumour or a stroke
A 50 year-old man who smokes and has high blood pressure collapses at work. He is unable to speak or move the right side of his face and he is unable to move his right arm or leg. Where is the problem and what is a likely diagnosis?
In the brain
Stroke
What are the main causes of stroke? What part of the brian does it affect? What part of the body if affected as a result?
80% are infarct (blockage of a vessel)
20% haemorrhage
Can affect any part of the brain (including brain stem)
Tends to cause a problem on the other side to the brain lesion
What is contralateral brain damage?
Injury that causes a problem on the opposite side of the body to the damage
On what side of the brain would a stroke cause aphasia, and what is it?
Left side of the brain responsible for language so a stroke on the left side would cause aphasia (problems with communication)
What would a stroke affecting the middle cerebral artery cause?
Often results in weakness and loss of sensation on the other side
What would a stroke affecting the posterior cerebral artery cause?
Often affect the occipital lobe- result in visual loss on the contralateral side
What would a stroke affecting the anterior cerebral artery cause?
Often cause contralateral leg weakness
What would a stroke affecting the brain stem cause?
May cause problems with balance, eye movements, speech and swallowing (cranial nerves) and breathing
What are the types of acute stroke treatment? (2)
Intravenous thrombolysis (dissolve the clot) Intra-arterial thrombectomy (remove clot)
What are the methods used to prevent further stroke? (3)
Thin blood with aspirin
Treat diabetes and high cholesterol
Treat dangerously narrow carotid arteries
What techniques are used to diagnose neurological problems in the examination? (3)
Cognitive/ thinking abilities: ‘mini mental state examination’
Cranial Nerves: Smell, vision, eye movements, facial sensation and movements
Limbs: Power, coordination, reflexes and sensation
What is involved in a mini mental state examination? (5)
1) Orientation: What is the year, season, date, day, month? Where are we? (city, house number, street)
2) Registration: Name three objects, repeat three objects, remember three objects, count number of trials
3) Trials: Serial 7s (100-7-7etc) alternatively spell ‘world’ backwards
4) Recall: Three objects from 2
5) Language: Name a pencil and a watch, Repeat “no ifs, ands or buts”, follow a three-stage command, read and obey “close your eyes, write a sentence, copy a design”
What are the symptoms of Parkinson’s disease normally present on examination?
Slow, shuffling gait, stooped, loss of arm swing, pill-rolling tremor at rest, increased tone and cogwheeling, bradykinesia (slowed finger movements), micrographia (small writing)
What is Parkinson’s disease?
A slowly progressive degenerative disease affecting the basal ganglia.
The main clinical features are rigidity (stiffness), tremor (shaking) and bradykinesia (reduced movement)
There is a loss of neurones from the substantia nigra to the caudate and putamen (parts of the basal ganglia)
What is the neurotransmitter associated with Parkinson’s disease?
Dopamine
What are patients with Parkinson’s disease treated with? How does this work?
Levodopa
Able to cross the blood brain barrier, unlike dopamine, and is then converted to dopamine
What are the causes of stiffness and weakness in the lower limbs with brisk reflexes?
Spinal cord
- Spastic paraparesis
- Multiple myeloma
What are the causes of spastic paraparesis? (7)
1) Trauma
2) Inflammatory/ autoimmune (e.g. MS)
3) Neoplastic (e.g. spinal cord tumour, metastatic tumour)
4) Degenerative (motor neurone disease)
5) Vitamin Deficiency (B12)
6) Infection (e.g. syphilis, viral)
7) Vascular (Anterior Spinal Artery Thrombosis)
What is a multiple myeloma? How is it treated?
Tumour of plasma cells
Treated with radiotherapy and chemotherapy
What symptoms would be present in an examination of a patient with a peripheral nerve disorder?
Normal cognition
Normal cranial nerves
Normal upper limbs except for loss of sensation in a glove formation
Lower limbs very weak (worse distally) and floppy (decreased tone) with absent reflexes (Lower Motor Neurone)
Sensory loss in the legs in a stocking distribution
What are the causes of acute polyneuropathy? (4)
1) Infections (e.g. diphtheria)
2) Autoimmune (e.g. Guillain-Barre Syndrome or Acute Inflammatory Demyelinating Polyneuropathy)
3) Drugs (Chemotherapy)
4) Exposure to toxins (organophosphate insecticides)
What are the symptoms of GBS/AIDP? (Guillain-Barre syndrome or Acute Inflammatory Demyelinating Polyneuropathy)
Common cause of acute neuromuscular weakness
Clinical diagnosis
Progressive ascending sensorimotor paralysis with areflexia, affecting 1 or more limbs ad reaching nadir within 4 weeks
Patients may progress to almost complete paralysis and require ventilation
What is the mechanism of auto-immune acute polyneuropathy?
Unidentified antigens bind to myelin on an axon
Activate MAC (membrane attack complex) complement
Causes injury to the nerve
Macrophages bind to and break down myelin (macrophage scavenging)
What treatment is used for GBS/AIDP (Guillain-Barre syndrome or Acute Inflammatory Demyelinating Polyneuropathy)? (4)
1) ‘Immunotherapy’- Plasma exchange or intravenous immunoglobulin
2) Supportive including ventilation if necessary
3) Cardiac monitoring
4) Anticoagulation to prevent leg clots (and subsequent pulmonary emboli)
What investigations are conducted to diagnose neurological problems? (5)
1) Brain scans: CT and MRI
2) Cerebrospinal fluid (CSF): Lumbar puncture
3) Nerve conduction studies and electromyography (EMG)
4) Electroencephalogram (EEG) and evoked potentials
5) Brain pathology: damage to cells or larger structures
What forms of syndromic formulations are used for diagnosing neurological problems? (5)
1) Clinical facts: history and examination
2) Interpretation in terms of physiology/anatomy
3) Syndromic formulation and lesion localisation
4) Anatomic diagnosis + mode of onset
5) Use investigations to confirm or refute clinical judgement
What is a neuron? What are it’s main features?
A neuron is a highly organised, metabolically very active secretory cell that is the basic structural and functional unit of the nervous system
- Large, prominent nucleus
- Abundant rough ER
- Well developed Golgi
- Abundant mitochondria
- Highly organised cytoskeleton
What are dendrites?
The major area of reception of incoming information on a neuron. Spreads from cell body and branches frequently, greatly increasing the surface area of the neuron.
Often covered in protrusions called spines which receive the majority of synapses
What part of a dendrite receive the majority of synapses?
Spines
Where are Purkinje neurons located?
In the cerebellum
What are axons? Where do they emerge from? How many per cell? What are the prominent features?
Conduct impulses away from cell body. They emerge from the axon hillock. Usually only one per cell but may branch after leaving the cell body, and at target. Has prominent microtubules and neurofilaments (intermediate filaments)
What are the two types of axon terminal?
Boutons
Varicosities
What type of transport shops synaptic vesicles from the Golgi in a synapse?
Anterograde transport
What happens to competing inputs in a postsynaptic neuron?
(Neuronal) integration
What are the types of synapse and their action? (3)
1) Axo-dendritic (often excitatory)
2) Axo-somatic (often inhibitory)
3) Axo-axonic (often modulatory)
What types of protein filament make up the cytoskeleton of neurons?
Microfilaments, intermediate filaments and microtubules
Neurofilaments play a critical role in determining axon caliber
Mircotubules are very abundant in the nervous system
What is a pseudounipolar neuron?
A sensory neuron with two fused processes which are axonal in structure
What is a bipolar neuron?
An neuron with two axonal processes
What is a Golgi type I multipolar neuron? Give 4 examples of where these axons are found
A neuron with highly branched dendritic trees and axons that extend long distances
e.g. pyramidal cells of the cerebral cortex, Purkinje cells of the cerebellum, anterior horn cells of the spinal cord and retinal ganglion cells
What is a Golgi type II multipolar neuron? Give 2 examples of where these axons are found
A neuron with highly branched dendritic trees and short axons
e.g. axons that terminate quite close to cell body of origin and stellate cells of the cerebral cortex and cerebellum
What are the three types of neuron?
1) Sensory neurons
2) Motor neurons
3) Interneurons
What are interneurons?
Responsible for modification, coordination, integration, facilitation and inhibition of sensory input
What are neuroglia?
The support cells of the nervous system with many and varied function, essential for the correct functioning of neurons
What are the types of neuroglia? ( 7)
1) Astroglia
2) Oligodendroglia
3) Microglia
4) Immature progenitors
5) Ependymal cells
6) Schwann cells
7) Satellite glia
What are astroglia?
A multi-processed star-like shape cell, the most numerous type of neuroglia. Gap junctions suggest astroglia-astroglia signalling
Contains numerous intermediate filament bundles in the cytoplasm of fibrous astroglia (GFAP)
What are the functions of astroglia? (9)
1) Scaffold for neuronal migration and axon growth during development
2) Formation of blood-brain barrier
3) Transport of substances from blood to neurons
4) Segregation of neuronal processed (synapses)
5) Removal of neurotransmitters
6) Synthesis of neurotrophic factors
7) Neuronal-glial and glial-neuronal signalling
8) Potassium ion buffering
9) Glial scar formation
What is an oligodendroglia? What are their characteristic features?
The myelin-forming cells of the CNS
Small spherical nuclei with a few thin processes. Prominent ER and Golgi and metabolically highly active
What are the two types of oligodendroglia?
Interfasicular oligodendroglia
Perineuronal oligodendroglia
What is the main function of oligodendroglia?
Production and maintenance of multiple (1-40) myelin sheaths
What is myelin?
A lipid-rich insulating membrane made up of up to 50 lamellae
Dark and light bands visible at EM level
Give two examples of diseases associated with myelin
Multiple sclerosis
Adrenoleucodystrophy
What are microglia? What are their main functions?
Resident macrophage population of the CNS involved in immune surveillance. They present antigens to invading immune cells and are the first cells to react to infection or damage. They have a role in tissue remodelling and synaptic stripping
What are the peripheral glial cells?
Schwann cells
What are Schwann cells?
Myelin-producing cells of the PNS. Each Schwann cell only produces one myelin sheath. they surround unmyelinated axons and promote axon regeneration
What is flux?
The number of molecules that cross a unit of area per unit of time
What are the unit of measurement of:
1) Voltage
2) Current
3) Resistance?
1) Volts
2) Amps
3) Ohms
What is membrane potential? What is a normal value?
The voltage difference on the inside of the cell compared to the outside
-70mV
At rest is Na+ or K+ permeability greater?
K+»Na+
What is the Nernst equation used to calculate?
Equilibrium potential
What is the Goldman- Hodgkin- Katz (GHK) equation used to calculate?
The resting membrane potential while considering the permeability of the membrane to each ion
What is a graded potential? Where is it strongest?
They occur at synapses and sensory receptors. They contribute to initiating or preventing action potentials and are strongest at the stimulation site
Give three examples of where an action potential will occur.
In a neuron
In a muscle cell initiating contraction
In pancreatic β-cells, provoking the release of insulin
What are the phases of an action potential?
1) Resting membrane potential
2) Depolarising stimulus
3) Upstroke (Depolarisation)
4) Repolarisation
5) After Hyperpolarisation
Where does the upstroke phase of an action potential start? (voltage)
At the threshold (∼-55mV)
At what voltage does repolarisation begin?
+30mV
What is the absolute refractory period? What channel causes this? In what phase of an action potential does it occur?
The period in which a new action potential cannot be triggered, even with a very strong stimulus
Occurs in repolarisation
At the start of repolarisation Na+ inactivation gate is closed- Na+ activation gate is open however later in repolarisation both gates are closed
What is the relative refractory period? What channel is involved in this? In what phase of an action potential does it occur?
Where a stronger than normal stimulus is required to trigger an action potential
Occurs in after-hyperpolarisation
Na+ activation gate is closed- Na+ inactivation gate is open
What affects the conduction velocity? How does it affect it?
Axon diameter: ↑ with axon diameter- less resistance to current flow inside a large diameter axon
Myelination: Higher in myelinated than non-myelinated axons of the same diameter- action potentials only occur at nodes of Ranvier
What slows conduction velocity?
Reduced axon diameter (i.e. regrowth after injury)
Reduced myelination (i.e. multiple sclerosis and diphtheria)
Cold, anoxia, compression and drugs (some anaesthetics)
How big is the gap between presynaptic nerve ending and postsynaptic region?
20-100nm
What part of a neuron is the postsynaptic region?
Dendrite of cell soma
What are the three stages of synaptic transmission?
1) Biosynthesis, packaging and release of neurotransmitter
2) Receptor action
3) Inactivation
What is required for transmitter release in synaptic transmission?
An increase in intracellular calcium
What is the process of synaptic transmission starting with membrane depolarisation?
1) Membrane depolarisation
2) Ca2+ channels open
3) Ca2+ influx
4) Vesicle fusion
5) Vesicle exocytosis
6) Transmitter release
What mechanism ensures rapid release of neurotransmitters occurs?
1) Synaptic vesicles are filled with neurotransmitter and docked in the synaptic zone “primed”
2) Ca2+ entry activates a Ca2+ sensor in the protein complex
3) Interaction between synaptic vesicles and synaptic membrane proteins allows rapid response
Give 4 examples of neurotoxin and their mechanism of action
1) Tetanus toxin: C. tetani causes paralysis
2) Zn2+-dependent endopeptideases: inhibit transmitter release
3) Botulinum toxin: C.botulinum causes flacid paralysis
4) α-Latrotoxin (black widow spider): stimulates transmitter release to depletion
What neurotransmitter receptors transmit fast and slow action?
Fast: Ion channel receptor- mediates all fast excitatory and inhibitory transmission
Slow: G-protein coupled receptor- effectors may be enzymes (adenyl cyclase, phospholipase C, cGMP-PDE) or channels (e.g. Ca2+ or K+)
Give examples of ion channel receptors in the CNS.
Glutamate
GABA (Gamma amino butyric acid)
Give examples of ion channel receptors in the NMJ.
Acetylcholine (ACh) at nicotinic receptors
Give examples of G-protein coupled receptors in the CNS and PNS.
Acetylcholine (ACh) at muscarinic receptors, dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5HT) and neuropeptides (e.g. enkephalin)
Considering glutamate and GABA are they excitatory or inhibitory?
Glutamate: excitatory
GABA: inhibitory
What glutamate receptor is involved in the majority of fast excitatory synapses?
AMPA receptors
(α-amino-3-hydroxy-5-methyl-4-isoxazole propanoic acid)
Majority of fast excitatory synapses. Rapid onset, offset and desensitisation
What glutamate receptor is the slow component of excitatory transmission?
NMDA receptors
(N-methyl-D aspartate)
Serve as coincidence detectors which underlie learning mechanisms
How is glutmate recycled after binding it’s receptor?
Glutamate→Glutamine (Glutamine synthetase) in glial cells
Abnormal cell firing leads to seizures associated with excess what in the synapse?
Glutamate
Abnormal neuronal excitability causes what condition?
Epilepsy
Hw is GABA recycled after binding it’s receptor
GABA→Succinate semialdehyde (GABA transaminase GABA-T)
What drugs facilitate GABA transmission? (4)
Antiepileptic
Anxiolytic
Sedative
Muscle relaxant
What is the focus of epilepsy treatment?
Dampening down excitatory activity by facilitating inhibitory transmission
What is a seizure?
A transient alteration of behaviour due to the disordered, synchronous and rhythmic firing of populations of brain neurones
Where do seizures arise? What is the difference between partial seizures and generalised seizures?
Seizures arise from the cerebral cortex
Partial seizures: beginning focally at a cortical site
Generalised seizures: involve both hemispheres widely from the outset
How would a seizure involving the motor cortex present?
Associated with clonic jerkig of the body part controlled by this region of the cortex
How does a simple partial seizure present?
Associated with preservation or consciousness
How does a complex partial seizure present?
Associated with preservation of consciousness
What are the types of generalised seizure?
Absence
Myoclonic
Tonic-colonic
What causes seizures? (neurotransmitters)
Decrease in GABA-mediated inhibition
Increase in glutamate-mediated excitation in the brain
What is the cellular mechanism and main uses of valproate?
Mechanism: Weak effect on GABA transaminase and on Na+ channels
Uses: Most types, especially absence seizures
What is the cellular mechanism and main uses of phenobarbital?
Mechanism: Enhanced GABA action. Inhibition of synaptic excitation
Uses: All types except absence seizures
What is the cellular mechanism and main uses of benzodiazepines? Give examples of these
Mechanism: Enhanced GABA action
Uses: All types. Diazepam used i.v. to control status epilepticus
e.g. clonazepam, clobazam, diazepam
What is the cellular mechanism and main uses of vigabatrin?
Mechanism: Inhibits GABA transaminase
Uses: All types. Appears to be effective in patients resistant to other drugs
What are the functions of the diencephalon?
Contains several nuclei with different function:
Thalamus acts as a relay station for the cerebral cortex
Hypothalamus coordinates homeostatic mechanisms
What are the functions of the cerebral hemispheres?
Basal ganglia: involved in control of movement
Cerebral cortex: involved in all functions
Corpus callosum: interconnects corresponding parts of 2 hemispheres across midline
What does the central sulcus divide?
Frontal and parietal lobe