Neurology Flashcards
How many cranial nerves are there?
12
What is the brainstem?
The part of the CNS, exclusive of the cerebellum, that lies between the cerebrum and the spinal cord
Medulla oblongata
Pons
Midbrain
What is not bilateral in the brainstem?
The pineal gland
What is bells-palsy?
Face drooping, post-infection
Why do we have contralateral function? Where does it originate?
There is crossing over of 95% of nerves in the pyramidal decussation
Where are the sensory and motor nuclei located in the brainstem?
Sensory nuclei are lateral and motor nuclei are medial
What is one of the first areas to be damaged in Parkinson’s disease?
Substantia nigra
Where are transverse fibres located in the brainstem?
The pons
What does the pons provide the floor of?
The fourth ventricle
At what point does the brainstem start to look like spinal cord?
In the lower medulla
What are the symptoms of lateral medullary syndrome?
Vertigo
Ipsilateral cerebellar ataxia (same side loss of control of body movements)
Ipsilateral loss of pain/ thermal sense (face)
Horner’s syndrome (drooping eyelid; loss of sympathetic tone to the head and neck)
Hoarseness, difficulty swallowing
Contralateral loss of pain/ thermal sense (trunk and limbs)
How much of the body’s cardiac output is used by the brain?
10-20%
How much of the body’s O₂ consumption is used by the brain?
20%
How much of the body’s liver glucose is used by the brain?
66%
Where does the brain’s blood supply come from?
Internal carotid arteries
Vertebral arteries
Where does the vertebral artery originate?
From the subclavian artery
What do the vertebral arteries join to form?
The basilar artery
What is the only unpaired artery in the circle of Willis?
The anterior communicating artery
In what vessel does all blood drained from the brain end up?
The internal jugular vein
What is a stroke?
A rapidly developing focal disturbance of brain function of presumed vascular origin and of >24 hours duration
What is the main cause of stroke? (and percentage occurrence)
Infarction (85%)
Haemorrhage (15%)
What is a transient ischaemic attack?
A rapidly developing focal disturbance of brain function of presumed vascular origin that resolves completely within 24 hours.
Often the precursor to a stroke
What is infarction?
Degenerative changes which occur in tissue following occlusion of an artery
What is cerebral ischaemia?
Lack of sufficient blood supply to nervous tissue resulting in permanent damage if blood flow is not quickly restored. Hypoxia is a component of ischaemia
What are the possible causes of occlusions?
1) Thrombosis
Formation of a blood clot (thrombus)
2) Embolism
Plugging of a small vessel by material carried from larger vessel (e.g. thrombi from the heart or atherosclerotic debris from the internal carotid)
What are the main risk factors for stroke?
Age Hypertension Cardiac disease Smoking Diabetes mellitus
What does the middle cerebral artery supply?
Most of the lateral aspect of the brain
What does the anterior cerebral artery supply?
Supplies the frontal lobe all the way back to the parietal-occipital fissure
What would occlusions of the anterior cerebral artery cause?
Paralysis of the contralateral leg > arm, face
Disturbance of intellect, executive function and judgement (abulia)
Loss of appropriate social behaviour
What would occlusion of the middle cerebral artery cause?
A “classic stroke”
Contralateral hemiplegia: arm > leg
Contralateral hemisensory (loss of sensation) deficits
Hemianopia (blindness over half the field of vision)
Aphasia (confuses similar sounding words) (L-sided lesion)
What would occlusion of the posterior cerebral artery cause?
Visual deficits:
- Homonymous hemianopia
- Visual agnosia (Loss of ability to recognise things)
What are the different types of haemorrhagic stroke? (4)
1) Extradural
2) Subdural
3) Subarachnoid
4) Intracerebral
What commonly causes an extradural stroke? When are you likely to present?
Trauma, rupture of the vessels supplying the dura- shows immediate effects
What commonly causes a subdural stroke? When are you likely to present?
Trauma- shows delayed effects
What commonly causes a subarachnoid stroke?
Ruptured aneurysms
What commonly causes an intracerebral stroke?
Spontaneous hypertensive
What type of haemorrhage results from a venous bleed and can take hours to present?
A subdural haemorrhage
If a patient has a sudden onset of stroke symptoms what does this suggest as the cause?
An occlusion of a vessel
A patient presents with sudden developed right-sided weakness and language dysfunction. They can understand verbal commands but cannot move their right arm and leg when asked to do so. What artery has become occluded?
Middle vertebral artery
If a patient presents with stroke symptoms that worsen over time what does this suggest is the cause?
A haemorrhage
Insufficient oxygen delivery to the brain causing function to become significantly impaired occurs when blood flow is reduced by how much?
More than 50%
If cerebral blood flow is interrupted unconsciousness will result after how long?
4 seconds
What is syncope?
Fainting
If blood glucose concentrations fall below what level unconsciousness, coma and death will result?
2mM
Total cerebral blood flow is autoregulated between what mean arterial blood pressures?
60-160 mmHg
How does the stretch-sensitive cerebral vascular smooth muscle respond to high and low blood pressure?
High BP: Contracts
Low BP: Relaxes
What happens if the blood pressure increases above the autoregulated range? What pressure is this?
If the blood pressure increases above 160 mmHg increased flow can lead to swelling of brain tissue, which is not accommodated by the closed cranium. This increases intracranial pressure - dangerous!
What controls the local regulation of cerebral blood flow?
Neural control
Chemical control
What neural factors regulate local cerebral blood flow?
1) Sympathetic nerve stimulation (at high BP)
2) Parasympathetic (facial nerve) stimulation
3) Central cortical neurones
4) Dopaminergic neurones
What are pericytes?
A form of brain macrophage with diverse activities. They have important functions in maintaining capillary integrity and function.
Peripheral vessels have sparse pericyte coverage, while BBB capillaries have dense pericyte coverage
e.g. immune function, transport properties, contractile
What parts of the brain are innervated by dopaminergic neurones? What do they do?
Innervate penetrating arterioles and pericytes around capillaries
May participate in the diversion of cerebral blood to areas of high activity
May cause contraction of pericytes via aminergic and serotoninergic receptors
How does sympathetic nerve stimulation regulate local cerebral blood flow?
Produces vasoconstriction; probably only when arterial blood pressure is high
How does parasympathetic nerve stimulation regulate local cerebral blood flow?
Produces slight vasodilation
How do central cortical neurones contribute to the regulation of cerebral blood flow?
Release a variety of vasoconstrictor neurotransmitters such as catecholamines
What chemical factors influence the regulation of cerebral blood flow, causing vasodilation?
CO₂, pH, NO, K⁺, adenosine, anoxia and others
What produces CSF?
Choroid plexus
What is the normal volume of CSF?
80-150ml
What are the functions of CSF?
Protection (physical and chemical)
Nutrition of neurones
Transport of molecules
How do blood-brain barrier capillaries prevent solute and fluid leak across the capillary wall?
They have extensive tight junctions at the endothelial cell-cell contacts
What kind of molecules can cross the blood-brain barrier? Give examples. How are they removed from the CNS?
Lipophilic molecules (e.g. O₂, CO₂, alcohol and anaesthetics) Removed directly via diffusion down concentration gradients
What are the circumventricular organs? What are these areas usually involved in? Give example of areas with these properties
Areas in the brain, close to the ventricles, that lack the blood-brain barrier properties. Their capillaries are fenestrated.
These areas of the brain are generally involved in secreting into the circulation, or where the plasma needs to be sampled
e.g. the posterior pituitary and median eminence secrete hormones; area postrema samples the plasma for toxins and will induce vomiting
Why did the old-fashioned H1 blockers make patients feel drowsy? How do the second generation antihistmaines prevent this?
They are hydrophobic and could cross the BBB. Histamine is important in wakefulness and alertness, so these antihistamines made people feel drowsy. Now used as sedatives.
Second generation antihistamines are polar and therefore do not readily cross the BBB
How does the BBB affect the use of dopamine in the treatment of Parkinson’s disease?
A key therapy in Parkinson’s disease is pharmacologically raising the level of dopamine in the brain. Dopamine cannot cross the BBB so L-DOPA must be used instead as it can cross the BBB via an amino acid transporter, to then be converted to dopamine in the brain.
Circulating L-DOPA is also converted to dopamine peripherally, so very little is able to access the brain. L-DOPA must be co-administered with the DOPA decarboxylase inhibitor Carbidopa, which cannot cross the BBB, so does not affect the conversion in the brain
What are the two major parts of the diencephalon?
Thalamus
Hypothalamus
What is the thalamus?
A collection of several large nuclei that serve as synaptic relay stations between the cerebral cortex and the rest of the CNS
It is an important integrating centre for most inputs to the cortex
Key role in:
- general arousal
- focussed attention
Divided into right and left thalamus by the third ventricle connected by the intermediate mass. Ipsilateral connections with the two hemispheres (no interaction across the midline)
What is the ventral lateral nucleus connected to? What is it’s function?
Connected with the motor corticles (primary, premotor and supplementary)
Helps to function in coordination and planning of movement, and in learning movement
What is the ventral anterior nucleus connected to? What is it’s function?
Connected with the motor corticles (primary, premotor and supplementary)
Helps to function in planning movement, and initiates wanted movement and inhibits unwanted movement
What is the ventral posterolateral nucleus connected to? What is it’s function?
Connected with the primary somatosensory cortex for the body
It sends touch and proprioceptive information to the primary somatosensory cortex from the body
What is the ventral posteromedial nucleus connected to? What is it’s function?
Connected with the primary somatosensory cortex for the head
It sends touch and proprioceptive information to the primary somatosensory cortex from the head
What is the lateral geniculate nucleus connected to? What is it’s function?
Connected with the visual system, sending information to the primary visual cortex in the occipital lobe
What is the medial geniculate nucleus connected to? What is it’s function?
Connected with the auditory system, acting as a key auditory relay between the inferior colliculus of the midbrain and the primary auditory cortex
What do the anterior, lateral dorsal and dorsomedial association nuclei connect to?
Parts of the limbic system
cingulate and prefrontal cortex
What do the lateral posterior and pulvinar association nuclei connect to?
Connect with the association cortex at the parieto-temporo-occipital junction and the prefrontal cortex
What are intralaminar nuclei? What are they part of? Where do they receive input from?
Small nuclei embedded in the lamina dividing the thalamus
They form part of the reticular activating system; responsible for the control of the level of arousal of the brain by modulating the level of activity of the cerebral cortex
They receive inputs from the reticular formation of the brainstem, and then project diffusely throughout the cortex
What nuclei receive inputs from the reticular formation of the brainstem?
Intralaminar nuclei
Reticular nuclei
What is the structure of the reticular nucleus?
A fine sheet of neurotissue that lies over the lateral surface of the thalamus like a net (has good access to other thalamic nuclei, but no direct connections with the cerebral cortex)
What is thalamic syndrome? What causes it?
Caused by cerebrovascular events (e.g. strokes)
Results in contralateral hemianaesthesia, burning or aching sensations on one-half of the body, often accompanied by mood swings. Sensation if reduced, exaggerated or altered and there is emotional disturbance (e.g. depression)
Where is the hypothalamus located?
Below and anterior to the thalamus
Posterior to the optic chiasm and pituitary infundibulum
What do the paraventricular nucleus and supraoptic nucleus contain?
Contains oxytocin and vasopressin neurones which project into the posterior pituitary
Contains neurones which regulate ACTH and TSH secretion from the anterior pituitary, as well as gastric reflexes, maternal behaviour, blood pressure, feeding, immune responses and temperature
How does the hypothalamus coordinate homeostatic mechanisms?
1) The autonomic nervous system
(via connections with the brainstem and spinal cord)
2) The endocrine system
(via the pituitary)
3) Controlling behaviour
(via connections with forebrain structures)
What forebrain structures are associated with the hypothalamus?
Olfactory system Limbic system (hippocampus, amygdala, cingulate cortex, septal nuclei)
What is the hypothalamus responsive to? (7)
1) Light
2) Olfactory stimuli
3) Steroids
4) Neural information
5) Autonomic inputs
6) Blood-bourne stimuli
(like leptin, ghrelin, angiotensin, insulin, pituitary hormones, cytokines etc)
7) Stress
What behaviours does the hypothalamus control?
1) Eating/drinking behaviours via appetite sensors 2) Emotion 3) Sexual behaviour 4) Circadian rhythm controlled by light-sensitive nuclei 5) Memory
What are the cranial nerves?
1) Olfactory nerve
2) Optic nerve
3) Occulomotor nerve
4) Troclear nerve
5) Trigeminal nerve (V1, V2 and V3)
6) Abducent nerve
7) Facial nerve
8) Vestibulococclear nerve
9) Glossopharyngeal nerve
10) Vagus nerve
11) Accessory nerve
12) Hypoglossal nerve
What foramen does each cranial nerve exit the skull from?
1) Cribriform plate of the ethmoid bone
2) Optic Canal
3/4/6) Superior orbital fissure
5) V1- Superior orbital fissure
V2- Foramen rotundum
V3- Foramen ovale
7) Internal acoustic meatus to stylomastoid foramen
8) Internal acoustic meatus
9/10/11) Jugular foramen
12) Hypoglossal canal
Which nerve is the only one to exit dorsally?
Troclear nerve
Which cortical areas are supplied by the middle cerebral artery?
Primary motor cortex for face Primary motor cortex for arm Primary somatosensory cortex for arm Primary auditory cortex Broca's area Wernicke's area
Which cortical areas are supplied by the anterior cerebral artery?
Primary motor cortex for foot
Which cortical areas are supplied by the posterior cerebral artery?
Primary cerebral artery
What are the differences in size and shape between C5 and L5 vertebrae?
C5 is larger and more oval-shaped
What are the differences in the proportion of white to grey matter between C5 and L5 vertebrae?
Greater proportion of white matter at C5 as all descending and ascending tracts must pass through this area
What is the cuneate fasciculus? What is the difference between this in the C5 and L5 vertebrae?
Touch and proprioception from upper limb
Present in C5 but not in L5
What anatomical feature distinguishes the thoracic sections from other levels of the cord?
The presence of the intermediolateral column, which contains the cell bodies of the preganglionic sympathetic neurones
What are Betz cells? How does their structure support their function?
Upper motor neurones
They have a large cell body to support their long projection axons down to the ventral horn of the spinal cord
What is the distinguishing feature of layer 1 of the cerebral cortex?
It has very few neurones, just fibres and glial cells
What is the role os mechanoreceptors?
Touch - light touch - pressure - vibration Proprioception - joint position - muscle length - muscle tension
What defines a tickle?
Relatively mild stimulation caused by something moving across the skin. May be pleasurable
Wher can tickling occur?
At areas of the body with naked unmyelinated afferent nerve fibres
What defines an itch?
An annoying local mechanical stimulation or chemical agent (e.g. histamine, kinins)
Relieved by scratching- stimulation of large nerve fibres overwhelms spinal transmission (closes the Gate)
Occurs in neuropathy, renal failure, dermatitis
What receptor is responsible for the cool feeling you get when eating mint?
Trpm8
What it Trpv1 receptor sensitive to?
Activated by >42°C, <17°C and chilli
Causes the burning feeling in extremem cold
What results from the loss of function mutation NaV1.7?
Born with an inability to feel pain- very rare
What is the nociceptor stimulus threshold? Is it the same in every individual?
The weakest stimulus required to elicit a specific response or reflex
Varies in relation to anatomical location, and inter-individual differences (low/high pain threshold)
What determines the stimulus intensity?
Determined by:
- Frequency of action potentials generated
- Number of separate receptors activated
What is recruitment of sensory neurones?
Where adjacent sensory neurones are activated when stimulus intensity increases
What is lateral inhibition of neurones? Where is it mediated?
Where activation of one neural unit inhibits another. Allows pin-point accuracy in localisation of the stimulus
Mediated by interneurones within the dorsal horn of the spinal cord
What is two-point discrimination of neurones? Where is greatest and poorest?
The ability to detect that tewo stimuli are distinct from one another.
Weakest in the back (65mm)
Strongest in the fingers (2mm)
What is neural adaptation?
If a stimulus of constant strength is maintained for a period of time the frequency of action potentials diminishes
What type of receptor responds rapidly to neural adaptation?
Phasic receptors
What type of receptor responds slowly to neural adaptation?
Tonic receptors
What are the different nerve fibre types and their function?
α- Proprioception, somatic motor
β- Touch, pressure
γ- Motor to muscle spindle
δ- Pain, cold, touch
What is the function of C-type nerve fibres
Dorsal root- Pain, temperature, mechanoception
Sympathetic- Postganglionic sympathetic
What is the Cortical Homunculus?
A map of the body within the brain
Which nerve fibre transmits painful stimuli?
A-δ
Where is the dorsal root ganglion?
In the posterior spinal nerve root
Which of the following is not an example of a mechanoreceptor?
- Dermal plexus
- Pacinian corpuscle
- Papillary plexus
- Ruffini ending
- Lissauer’s corpuscle
Lissauer’s corpuscle
Where do pain and temperature pathways decussate?
In the spinal cord
Where do touch and proprioception pathways decussate?
In the brainstem
Wha is the Gate Control Theory?
A non-painful stimulus can inhibit transmission of a painful stimulus
What are the different types of pain? (6)
Nociceptive Muscle Superficial somatic Visceral Referred Neuropathic
What is the WHO analgesic ladder for cancer pain relief?
1) Paracetamol, aspirin and ibuprofen
2) Codeine and tramadol
3) Morphine
What is myalgia? What are the features of this type of pain?
Muscular pain
- aching
- burning
- cramping
- tightness
- crushing
- tenderness
Describe somatic pain. What are the features?
A type of nociceptor pain that is well localised (affects the skin).
- sharp
- stinging
- aching
- burning
- throbbing
- sensitive
What are dermatomes?
A section of the skin which corresponds to a nerve root from the spinal cord
Describe visceral pain.
Viscera have low-density of sensory innervation. Characteristically midline pain at level of the sternum/epigastrium.
Pain may be referred. Requires a multimodal treatment
What is hyperalgesia?
Increased pain from a stimulus that normally provokes pain
Hypersensitivity to pain
What is the wind-up phenomenon?
Where repetitive stimulation of wide dynamic range neurones induces increased evoked response and post-discharge with each stimulus
Describe neuropathic pain?
Pain in an area of neurological dysfunction. Has poor response to normal analgesic drugs. Can last after the area has healed completely
- sharp
- burning
- electric shock
- squeezing
What criteria is used to diagnose Complex Regional Pain Syndrome?
IASP Budapest criteria
What is Complex Regional Pin Syndrome?
Severe form of neuropathic pain with neurogenic inflammation
Overexpression of nociceptive endings
Treated with medication and spinal cord stimulation
What causes phantom limb pain?
Remapping of the cortical homunculus. Areas lying near to the area which controls the amputated limb begin to stimulate phantom limb pain
What drugs are used to treat neuropathic pain?
Antidepressants Anticonvulsants Opiod trial Hybrid (Tapentadol) Topical (e.g. Capsaicin)
How do capsaicin patches work to treat neuropathic pain?
Capsaicin binds to TRPV1 receptor on nerve endings allowing influx of calcium. Capsaicin has direct toxicity to mitochondria, which reduces the number of nerve endings
Nociceptive impulses are transmitted by which nerve fibres?
A-δ and C
What is allodynia?
Pain due to a stimulus that does not normally provoke pain
Functionally, what are the three areas of the cerebral cortex? Describe their function.
Sensory areas
- receive sensory information from the thalamus and include primary visual, primary auditory and primary somatosensory cortex
Motor areas
- concerned with motor control. Include the primary motor cortex (M1: executes voluntary movements) and the motor association cortex (which selects voluntary movements). Also motor functions have been described for the posterior parietal cortex and dorsolateral prefrontal cortex
Association areas
- include Brocke’s and Wernicke’s area. Function to produce a meaninful perceptual experience fo the world, enabling us to interact effectively and carry out abstract thinking and language
What is hierarchical organisation?
Where high order areas (somatosensory cortex, prefrontal cortex, motor association corticles, basal ganglia, thalamus, primary motor cortex and cerebellum) are involved in the more complex task of programming and planning movements, and coordinating muscle activity.
Lower level areas (brain stem and spinal cord) perform the execution of movement
What are the different areas of the motor cortex?
1) Primary motor cortex (M1)
2) Premotor cortex
3) Supplementary motor area
What is Broadmann’s area 4? Where is it located and what is it’s function? What cells are found in this area?
The primary motor cortex
Located in the frontal lobe on the precentral gyrus, anterior to the central sulcus
Function: controls (initiates) fine, discrete, precise voluntary movements. Provides the descending signals to execute movements
Contains Betz cells which send their axons down to the spinal cord via the corticospinal tract
What is innervated by the lateral corticospinal tracts?
Where do these axons decussate?
Innervates arms and legs
Decussates in the pyramidal decussations (medulla)
What is innervated by the anterior corticospinal tracts? Where do these axons decussate?
Innervates muscles of the front, back and proximal part of the limbs
Decussates in the spinal cord
What type of signalling is used to transmit signals from the brain all the way to the muscles?
Generation and propagation of an action potential along the axon in electrical
Impulse transmission is chemical mediated by neurotransmitters
What is in Broadmann’s area 6? Where are they located and what are their function?
Premotor Cortex
- Located in the frontal lobe anterior to the primary motor cortex
- Involved in planning movements; regulates externally cued movments
Supplementary Motor Area
- Also anterior to the primary motor cortex, but more medial
- Involved in planning complex movements and programming sequencing of movements. Regulates internally driven movements (e.g. speech)
What is located in the Association cortex?
Posterior Parietal Cortex
- ensures movements are targeted accurately to objects in external space
Prefrontal Cortex
- involved in selection of appropriate movements for a particular course of action
What are the positive and negative signs of an upper motor neuron lesion?
Loss of function (-)
- Paresis: graded weakness of movements
- Paralysis (plegia): complete loss of muscle activity
Increased abnormal motor function (+) (loss of inhibitory descending inputs)
- Spasticity: increased muscle tone
- Hyperreflexia: exaggerated reflexes
- Clonus: abnormal oscillatory muscle contraction
- Babinski’s sign
How are the tongue muscles innervated from the descending motor pathway?
Corticobulbar tract from the head region of the motor cortex; synapses with the hypoglossal nerve which innervates the tongue
What is apraxia? What causes this?
A disorder of skilled movement. Patients are not paretic but have lost information about how to perform skilled movement
Lesion of inferior parietal lobe, the frontal lobe (premotor cortex, supplementary motor area) can cause apraxia; stroke and dementia are the most common causes
What are the symptoms of a lower motor neuron lesion?
Weakness
Hypotonia (reduced muscle tone)
Hyporeflexia (reduced reflexes)
Muscle atrophy
Fasciculations: damaged motor units produce spontaneous action potential resulting in a visible twitch
Fibrillations: spontaneous twitching of individual muscle fibres, recorded during needle electromyography examination
What are the upper motor neuron signs of motor neuron disease?
- Increased muscle tone (spasticity of limbs and tongue)
- Brisk limbs and jaw reflexes
- Babinski’s sign
- Loss of dexterity
- Dysarthria
- Dysphagia
What are the lower motor neuron signs of motor neuron disease?
- Weakness
- Muscle wasting
- Tongue fasciculations and wasting
- Nasal speech
- Dysphagia
What part of the brain controls the execution of movements?
Primary motor cortex
What part of the brain controls the planning of movements?
Premotor cortex and the supplementary motor area
What part of the brain controls the selection and accuracy of movements?
Association cortex
What is the role of side loops in the motor hierarchy?
Brain circuits which “help” the cortical areas to smoothly regulate motor behaviours
What structures form the basal ganglia?
Striatum: caudate and putamen
Globus pallidus externa (GPe) and globus pallidus interna (GPi)
Substantia nigra pars compacta (SNc) and pars reticulata (SNr)
Subthalamic nucleus (STN)
What is the function of the basal ganglia?
- Elaborating associated movements (e.g. swinging the arms when walking, facial expression matching emotions)
- Moderating and coordinating movement (suppressing unwanted movements)
- Performing movements in order
Where does the striatum (in the basal ganglia) send and receive information from?
Receives input from many brain areas
Sends output only to other components of the basal ganglia
What is the pathway of the basal ganglia input and output?
Input from the cortex enter the putamen in the basal ganglia:
- Direct pathway: to the GPi and SNr (involving GABA)
- Indirect pathway: to the GPe via STN (involving GABA)
GPi and SNr are the only output from the basal ganglia with projections to the thalamus, and via the thalamus back to the cortex (supplementary motor area and premotor cortex)
How is the basal ganglia pathway inhibited or excited?
The globus pallidus and the substantia nigra inhibit the thalamus (GABA)
The putamen inhibits GPi and SNr which releases the thalamus from inhibition
The thalamus releases the selected movement through it’s projections into the cortex
The correct balance of excitation/inhibition of the thalamus is maintained by the SNc which provides excitatory inputs to the striatum (dopamine)
What are the different classes of syndromes that occur through damage to the basal ganglia?
Hypokinetic: decreased movement
(e.g. Parkinson’s disease)
Hyperkinetic: increased movement (Huntington’s disease)
What causes Parkinson’s disease?
Neuronal degredation of substantia nigra pars compacta causes loss of nigro-strial dopaminergic axons in striatum
>80% loss of dopamine cells
- disruption of the fine balance of excitation and inhibition
- reduction of the excitation motor cortex
What are the main signs of Parkinson’s disease?
Bradykinesia- slowness of (small) movements (doing up buttons, handling a knife)
Hypomimic face- expressionless, mask-like (absence of movements that normally animate the face)
Akinesia- difficulty in the initiation of movements because cannot initiate movements internally
Rigidity- Muscle tone increase, causing resistance to externally imposed joint movements
Tremor at rest- Starts in one hand (pill-rolling tremor), with time spreads to other parts of the body
Parkinsonian’s gait- walking slow, small steps, shuffling feet, reduced arm swing
Stooped posture- Head and body bent forward and downward
What is Huntington’s disease?
Neurodegenerative genetic disorder
Abnormality in chromosome 4. Autosomal dominant
Degeneration of GABAergic neurons in the striatum (caudate first then putamen later)
- disruption of fine balance between inhibition and excitation
- motor cortex gets excessive excitatory input
- motor cortex continuously sends involuntary commands for movements and movement sequences to the muscles
What are the main signs of Huntington’s disease?
Choreic movements (chorea): rapid jerky involuntary movements of the body. Hands and face affected first then legs and the rest of the body - Speech impairment - Difficulty swallowing - Unsteady gait Later on, cognitive decline and dementia
What are the three horizontal lobes of the cerebellum?
Anterior
Posterior
Flocculonodular
What are the three sagital zones of the cerebellum?
Vermis
Intermediate hemisphere
Lateral hemisphere
What side of the body and cerebral hemisphere is the cerebellum connected to?
Connected with:
SAME side of the body
OPPOSITE cerebral hemisphere
What are the main neurotransmitters in the cerebellum?
Glutamate (+)
GABA (-)
What lobe is the vestibulocerebellum? What is the function of this region?
The flocculonodular lobe
Function:
- regulation of gait, posture and equilibrium
- coordination of head movements with eye movements
What parts of the cerebellum make up the spinocerebellum? What inputs project into each area?
What is the function of the spinocerebellum?
Vermis: Spinal afferents from axial portions of the body, trigeminal, visual and auditory inputs Intermediate hemisphere: Spinal afferents from the limbs project to the intermediate hemisphere Function: Coordination of speech Adjustment of muscle tone Coordination of limb movements
What part of the cerebellum makes up the cerebrocerebellum? What is the function of this area?
The lateral hemisphere
Coordination of skilled movement
Cognitive function, attention processing of language
Emotional control
What is the function of the cerebellum?
1) Maintenance of balance and posture
2) Coordination of voluntary movements
3) Motor learning
4) Cognitive functions (language)
What causes and results from Vestibulocerebellar Syndrome?
Damage (tumour) causes syndrome similar to vestibular disease leading to gait ataxia and tendency to fall (even when sitting with eyes open)
What causes and results from Spinocerebellar Syndrome?
Damage (degeneration and atrophy associated with chronic alcoholism) affects mainly the legs, causes abnormal gait and stance (wide-based)
What causes and results from Cerebrocerebellar Syndrome?
Damage affects mainly arms/skilled coordinated movements (tremor) and speech
What are the main signs of cerebellar disorders?
Deficits apparent only on movement
- Ataxia: general impairments in movement, coordination and accuracy
- Dysmetria: inappropriate force and distance for target-direted movements
- Intention tremor: increasingly oscillatorytrajectory of a limb in a target-directed movement
- Dysdiadochokinesia: inability to perform rapidly alternating movements
- Scanning speech: staccato, due to impaired coordination or speech muscles
Give an example of hereditary and acquired cerebellar disorders.
Hereditary- Friederich’s Ataxia
Acquired- Multiple Sclerosis
How can the membrane potential of the post synaptic neurone be altered?
1) Made less negative (closer to activation threshold)- an excitatory post synaptic potential (EPSP)
2) Made more negative (further away from activation threshold)- inhibitory post synaptic potential (IPSP)
Graded effects- summation
What is the neuromuscular junction?
A specialised synapse between the motor neurone and the motor end plate, the muscle fibre cell membrane
How is the neuromuscular junction activated?
Action potential arrives at NMJ, Ca²⁺ influx causes ACh release. ACh binds to receptors on the motor end plate.
Ion channel opens- Na⁺ influx causes action potential in muscle fibre
What are miniature end-plate potentials?
Where at rest, individual vesicles release ACh at a very low rate
What are the alpha motor neurones?
The lower motor neurones of the brainstem and the spinal cord. They innervate the (extrafusal) muscle fibres of the skeletal muscles
Their activation causes muscle contraction
The motor neuron pool contains all alpha motor neurons innervating a single muscle
Where are alpha motor neurones located in the anterior horn in relation to the muscles they innervate?
Flexor muscles- posterior part of the horn (tend movement to the foetal position) e.g. biceps and hamstrings
Extensor muscles- anterior part of the horn (tend movement to straighten the body) e.g. triceps and quadriceps
Distal muscles- lateral part of the horn e.g. muscles of fingers
Proximal part of the horn- medial part of the horm e.g. muscles of the trunk
What is a motor unit?
A single motor neuron together with all the muscle fibres that it innervates
What are the different types of motor neuron? How are they classified?
3 typres classified by the amount of tension generated, speed of contraction and fatigability of the motor unit
- Slow (S, type I)
- Fast, fatigue resistant (FR, type IIA)
- Fast fatiguable (FF, type IIB)
Starts with the smallest diameter cell bodies, smallest dendritic tree, thinnest axon and slowest conduction velocity- gets faster as moving down the groups
What are the two mechanisms by which the brain regulates the force that a single muscle can produce?
Recruitment
Rate coding
What is the recruitment method of regulation of muscle force?
“Size principal”- smaller units are recruited first (these are generally the slow twitch units). As more force is required, more units are recruited
This allows fine control (e.g. when writing), under which low force levels are required
What is the rate coding method of regulation of muscle force?
A motor unit can fire at a range of frequencies. Slow units fire at a lower frequency. As the firing rate increases, the force produced by the unit increases
Summation occurs when units fire at frequency too fast to allow the muscle to relax between arriving action potential
What are neurotrophic factors?
Growth factors which prevent neuronal death and promote growth of neurons after injury
What are the effects of neurotrophic factors on muscle?
Motor unit and fibre characteristics are dependent on the nerve which innervates them. If a fast twitch muscle and a slow muscles are cross innervated the soleus becomes fast and the fast muscle becomes slow
What fibre type changes can occur in muscle? (plasticity of motor units)
Training: Type IIB to IIA (fatiguable to fatigue resistant)
Spinal cord injury/microgravity: Type I to type II
Aging: loss of type I and type II fibres; preferential loss of type II fibres- larger proportion of type I fibres in aged muscle
What is a reflex?
An automatic response to a stimulus that involves a nerve impulse passing inward from a receptor to a nerve centre and then outwards to an effector without reaching the level of consciousness
Magnitude and timing are determined by the intensity and onset of the stimulus
What are the components of a reflex arc?
1) Sensory receptor
2) Sensory neuron
3) Integrating centre
4) Motor neuron
5) Effector (muscle or gland)
What is the mechanism of the monosynaptic reflex?
1) Stretching stimulates sensory receptor (muscle spindle)
2) Sensory neuron excited
3) Within integrating centre (spinal cord) sensory neurone activates motor neuron
4) Motor neuron excited
5) Effector (same muscle) contracts and relieves the stretching
( Motor neuron to antagonistic muscles is inhibited)
What is the mechanism of the flexion withdrawal (polysynaptic) reflexes?
1) Stepping on glass stimulates sensory receptor (dendrites of pain-sensitive neuron)
2) Sensory neuron excited
3) Within integrating centre (spinal cord) sensory neuron activates interneurons in several spinal cord segments
4) Motor neurons excited
5) Effectors (flexor muscles) contract and withdraw leg; other leg extends to maintain balance and upright position
How does supraspinal control influence reflexes?
Higher entres of the CNS exert inhibitory and excitatory regulation upon the stretch reflex.
In normal conditions the inhibitory control dominates
Rigidity and spasticity can result from brain damage giving overactive or tonic stretch reflex
how can higher centres influence reflexes? (5)
1) Activating alpha motor neurons
2) Activating inhibitory interneurons
3) Activating propriospinal neurons
4) Activating gamma motor neurons
5) Activating terminals of afferent fibres.
What higher centres and pathways are involved in supraspinal control of reflexes?
Cortex- corticospinal (fine control of limb movements, body adjustments)
Red nucleus- rubrospinal (automatic movements of arm in response to posture/balance)
Vestibular nuclei- vestibulospinal (altering posture to maintain balance)
Tectum- tectospinal (head movements in response to visual information
What is the gamma reflex loop?
When the joint is extended and the muscle goes slack the spindle is shortened to maintain it’s sensitivity
What is hyporeflexia?
below normal or absent reflexes
Mostly associated with lower motor neuron diseases
What is Brown-Séquard syndrome?
Damage to one-half of the spinal cord resulting in ipsilateral paralysis and loss of proprioception and contralateral loss of pain and temperature sensation
What causes jerking movements in a patient who has had a stroke?
Caused by too much glutamate being released. The site of the infarct is an epileptic focus. The levels of ATP cannot be controlled; glutamate is ATP dependent so too much is being released.
Which pathways are affected in Locked In syndrome?
Lesion at the level effecting corticospinal and corticobulbar tracts to spinal and brain stem. The abducens nucleus is effected (lateral eye movement lost)
UPPER PONS
Below the oculomotor nucleus is intact (vertical eye movement)
Where is the lesion that causes Locked In Syndrome? Why are sensation and consciousness not affected?
Occlusion of the basilar artery which supplies regions in the pons.
Ventral (anterior) brain stem (ascending sensory and reticular formation spared)
Internal carotid artery and circle of Willis supply forebrain and midbrain
