GEP (Life Control) Week 4 Flashcards
What are the layers of the Mininges
Dura Mater
* Most external
* Foramen magnum to filum terminale
Arachnoid mater
* Middle layer
* Separated from pia mater by subarachnoid space, which is CSF containing
**Pia mater **
* Innermost layer
* Inferiorly, fuses with filum terminale
What are spinal nerves (overview)
**Spinal Nerves **
* Mixed nerves that originate from the spinal cord, forming the PNS
* Each nerve begins as an anterior (motor) and posterior (sensory) nerve root
* Unite at intervertebral foramina to form a single spinal nerve
* Leaves vertebral canal and divides into
Posterior rami → synovial joints, deep muscles and overlying skin
Anterior rami → remaining area of the body
What are the functions of the Spinal Cord
The Spinal Tracts
← Sensory (ascending pathways)
Spinothalamic tract
* Pain, temperature and crude touch
* Decussates at vertebral level
* Lesions produce contralateral symptoms
Dorsal column
* Fine touch and proprioception
* Decussate in medulla
* Lesions produce ipsilateral symptoms
Motor (descending pathways) →
**Corticospinal tract **
90% decussation in medulla
Lesions produce ipsilateral symptoms
What is the structure of the brain stem
Midbrain
External → tectum and paired cerebral peduncles
Internal → inferior and superior colliculus levels
-There is much more to discuss here, but it is low yield.. Refer to Teach Me Anatomy if you need more info
Pons
External anatomy:
-Anterior surface → Cranial nerves V, VI, VII and VIII
-Posterior surface → Medial eminence, facial colliculus and stria medullaris
Internal anatomy:
-Ventral pons
-Tegmentum
**Medulla **
External anatomy:
3 fissures, pyramids, olives and cranial nerves VI, IX, X, XI and XII
Internal anatomy: - again, many cross sections, low yield for now
carry on questions from the brain stem
What is the brain stem function
**Many key life functions **→ breathing, consciousness, blood pressure, heart rate and sleep
Midbrain
* Centrally contains cerebral aqueduct
* Superior colliculus = visual reflexes, sending fibres to lateral geniculate body
* Inferior colliculus = auditory processing
* Cranial Nerves III and IV
Pons
* Cranial nerves V, VI, VII and VIII
* Pontine nuclei - many cerebellar connections that assist with coordination of movement and modulation of breathing
**Medulla **
* Pyramids - motor fibres
* Cranial nerves IX, X, XI and XII
* Connection to spinal cord
-Gracile and cuneate nuclei for motor function
What is the structure of the cerebellum
What is the function of the cerebellum
**Functional divisions vs Structural: **
Cerebrocerebellum
Largest area, involved in planning movements and motor learning
Also regulates coordination of muscle activation and is important in visually guided movements
Spinocerebellum
Regulating body movements, allowing for error correction and proprioceptive information
Vestibulocerebellum
Controls balance and ocular reflexes, mainly fixation on a target
Receives input from the vestibular system
Lesions in the cerebellum will be ipsilateral in their symptoms
REMEMBER DANISH FOR CEREBELLAR SIGNS:
DYSDIADOCHOKINSEA/DYSMETRIA
ATAXIA
NYSTAGMUS (HORIZONTAL)
INTENTION TREMOR
SLURRED SPEECH
HYPOTONIA
What is the basal ganglia and its structure
Basal Ganglia → group of subcortical structures found deep within the white matter of the brain, forming part of the extrapyramidal motor system. Also works in tandem with the pyramidal and limbic systems.
Consists of 5 pairs of nuclei:
- Striatum
Dorsal striatum → caudate nucleus and putamen
Ventral striatum → composed of nucleus accumbens and olfactory tubercle (this is the limbic system) - Globus pallidus
Consists of internal segment (GPi) and external segment (GPe) - Subthalamic nucleus
- Substantia nigra
What is the function of the basal ganglia
General function → fine tune voluntary movements
**Dorsal Striatum **
Caudate nucleus - integrates sensory information about the spatial position of the body and according to that, sends the information about necessary fine motor tuning to thalamus, predominantly using GABA
Putamen - regulates motor functions and influence various types of learning, using dopamine
Ventral striatum
Nucleus accumbens and olfactory tubercle
Involved in the reward circuit - increase in dopamine
Globus Pallidus
GABAergic projection neurons
Involved in constant subtle regulation of movements to create smooth and precise motor actions
Subthalamic nucleus
Glutaminergic neurons with mostly unknown function, but is motor
**Substantia nigra **
Small motor nucleus, where loss of D1 and D2 neurons = Parkinson’s
Cortex structure and function
What are reflexes
A reflex is defined as an involuntary, unlearned, repeatable, automatic reaction to a specific stimulus which does not require input from the brain
The muscle stretch reflex is the most basic reflex pathway in the body
What is Monosynapic strech reflex
Monosynaptic stretch reflex
* The pathway starts when the muscle spindle is stretched
* The muscle spindles are responsible for detecting the length of the muscles fibres
* When a stretch is detected, it causes action potentials to be fired by type 1a afferent fibres
* These then synapse within the spinal cord with α-motor neurons which innervate extensor muscle fibres
* Type 2 sensory neurons synapse with an interneuron, which inhibit α-motor neurons of the flexor muscle fibres
* The antagonistic muscle is inhibited, and the agonist muscle contracts
* The sensitivity of the reflex is regulated by gamma motor neurons – these lead to tightening or relaxing of muscle fibres within the muscle spindle
What are patterned Movement
Central pattern generators (CPGs)
* These are networks of cells that are capable of producing intrinsic motor responses even in the absence of sensory or brain inputs
* These motor responses are usually well-rehearsed, repetitive, and happen at the unconscious level, meaning that certain behavioural outputs can be performed independently of signals upstream in the motor cortex
* Central pattern generators:
-Originate in spinal cord
-Neurons sense stretch on one side and facilitates contraction of one muscle and relaxation of another
-There is interconnection of spinal segments allowing a timed response to the contractions
-There is also reciprocal communication between the spinal generator and the brain stem
What helps with the control of balance and posture
The vestibulocollic reflex (VCR)
Acts on the neck musculature in order to stabilize the head
Reflex head movement counters the movement sensed by the otoliths or semi-circular canals
The cervicospinal reflex (CSR)
Also known as the tonic neck reflex
Defined as changes in limb position driven by neck afferent activity
The cervicocollic reflex (CCR)
A cervical reflex that stabilizes the head on the body
Afferent sensory changes caused by changes in neck position, create opposition to that stretch by reflexive contractions of neck muscles
What are volitional (Voluntary) movements
At least 4 circuits commence in the cerebral cortex, traverse the Basal Ganglia and return to the cortex to regulate voluntary movement
- Motor Loop → Learned Movements (writing, passing a ball)
- Cognitive/associative Loop → Motor Intentions (preparing for movements)
- Limbic Loop → Emotional Aspects of movement
- Oculomotor Loop → Voluntary Saccades (using the eye muscles to look at an object)
Summary of the cranial nerves
Review of all the foramen in the head for cranial nerve
What is the dopaminergic pathway
Dopamine receptors
D1 → most abundant in CNS, mostly linked to direct pathway
D2 → less abundant, mostly linked to indirect pathway
**Pathways **
Mesocortical → connects ventral tegmentum to prefrontal cortex
Mesolimbic → known as the reward pathway, connects ventral tegmentum to ventral striatum of basal ganglia
Nigrostriatal → bilateral pathway, connects substantia nigra pars compacta with dorsal striatum
Tuberoinfundibular → connects the hypothalamus with the pituitary gland
Structure pathways and neurotransmitter for parkinsons
Neurotransmitters
Glutamate → excitatory in the CNS
GABA → inhibitory in the CNS
As mentioned earlier… basal ganglia are sub-cortical nuclear masses that lie in the inferior part of the cerebral hemisphere
We are interested in 2 pathways here, the direct and indirect pathways, that project onto the motor cortex of the brain for planned movements:
- Direct → starts from cortex, projects eventually to to the cortex and motor cortex, via the striatum, Medial Globus Pallidus (MGP) and the VA/VL nucleus of the thalamus
- Indirect → starts at the cortex, also eventually projects to the cortex and motor cortex, via the striatum, the Lateral Globus Pallidus (LGP), the subthalamic nucleus, then back to the Medial Globus Pallidus (MGP) and up to the VA/VL nucleus in the thalamus
- Dopamine from the indirect pathway helps excite the striatum to increase GABA inhibition to the lateral globus pallidus which in turn decreases motor cortex activity, vice versa. In parkinsons you have the substantia nigra releasing less dopamine leading to more motor cortex activity
- All this leads to motor cortex to send projections via the corticospinal tract to the muscle
Describe the direct and indirect pathways in the brain
Direct Pathway
* Striatum inhibits the Medial Global Pallidus (MGP) through a GABA pathway
* MGP inhibits the VA/VL nucleus
* VA/VL nucleus stimulates the motor cortex through glutamate pathway
* Motor cortex stimulates the muscles
IN SUMMARY:
-Increased striatum activity, decreases the MGP to a greater degree as more GABA is released
-This decreases the inhibitory effects of the MGP and therefore increases the VA/VL nucleus, increasing glutamate activity and increasing motor cortex activity
-SO more dopamine onto the striatum from substantia nigra produces the same effect
Indirect Pathway
* Striatum inhibits the Lateral Globus Pallidus (LGP)
* Inhibits the subthalamic nucleus less, which excites the MGP more
* MGP inhibits the VA/VL more, which excites the motor cortex less
https://www.youtube.com/watch?v=I4XXoiWwoNc
What is the pathophysiology and investigation for parkinsons
Parkinson’s disease is characterized by:
- Progressive degeneration of dopamine-producing neurons in the substantia nigra pars compacta
- Leading to dopamine deficiency in the basal ganglia
-Loss of dopamine to 20-40% of normal before symptoms are seen - This disruption of dopamine signaling results in abnormalities in motor control and other brain functions
-Reduced excitation of the direct pathway = reduced disinhibition of the thalamus = reduced movement
-Reduced inhibition of the indirect pathway = more inhibition of the thalamus = reduced movement
Investigations:
* Diagnosis of Parkinson’s disease is primarily based on clinical assessment, including a detailed medical history and neurological examination
* One of the best ways of establishing a diagnosis of PD in a patient with suggestive symptoms is a clear response to Levodopa treatment
Pathophysiology:
Surviving neurons often contain Lewy bodies (made of α-synuclein protein that has misfolded and aggregated)
Lewy bodies can be widespread throughout the brain which causes neuronal degeneration and dementia
20-40% of PD patients develop Parkinson’s disease dementia (PDD), usually 10-15 years after diagnosis
The primary aetiology appears to be the accumulation of alpha-synuclein in various parts of the brain, primarily the substantia nigra, leading to degeneration and subsequent loss of dopamine in the basal ganglia that control muscle tone and movement. The accumulation of the alpha-synuclein protein may be secondary to a genetic predisposition, such as with the PARK-1 mutation. There has been some recent interest in establishing an infectious etiology that triggers this alpha-synuclein accumulation after reports that the earliest degenerative change in PD appears in the myenteric plexus on the GIT, from where it progresses up to involve the dorsal motor nucleus of the vagus nerve, the sleep centers in the pons, and then the midbrain. This interesting theory also addresses why patients with PD typically suffer from gastrointestinal motility issues and REM sleep disorder, both of which can precede the motor manifestations of PD for many years.
Therefore, as our knowledge about the etiology of PD evolves, it is not enough to regard this disorder as primarily caused by a lack of dopamine in the substantia nigra. There appears to be a darker, more extensive pathophysiology behind this, and the non-genetic causes of alpha-synuclein deposition in the brain are a subject of active research.
Investigations:
MRI is useful in narrowing the differential and excluding other conditions that may present with a similar examination, such as normal pressure hydrocephalus or subcortical stroke. In certain situations, a DAT scan may be used to identify the loss of dopaminergic uptake in the basal ganglia. However, the interpretation of this test can be challenging, and the routine use of this test is to be discouraged. LP can be done to rule out normal pressure hydrocephalus.
How is dopamine synthesised
-Dopamine involved in control of BG
-Important role in motor function, reward-based learning, addiction and mood
-Synthesized in substantia nigra of midbrain, starts off with tyrosine, converted into L-DOPA (via TH) and then DA (via DDC), then packaged into vesicles and released into synaptic cleft, where has action in it’s receptors, then taken up into either presynaptic terminal or astrocytes, and broken into inactive metabolites by MAO-B of COMT
-Important to know about enzymes in above, as target for some of PD drugs
-Dopamine receptors are GPC receptors – 5 types (D1-D5)
D1-like (D1 and D5) are ‘S’ coupled, stimulatory, excitatory and depolarize neurons
D2-like (D2, D3, D4) are ‘I’ coupled, so inhibitory, so hyperpolarize neurons
What is the medication management for parkinsons
Primary mgmt: carbidopa (peripheral DOPA decarboxylase inhibitors) + levodopa (synthetic dopamine precursor)
Secondary mgmt: pramipexole OR ropinirole OR rotigotine transdermal (dopamine receptor agonists)
Tertiary mgmt: selegiline OR rasagiline OR safinamide (MAO-B inhibitors)
Varying the pharmacokinetics of levodopa has sometimes helped, such as newer formulations of delayed-release levodopa or a continuous GI pump infusion form of levodopa
