motor disorders Flashcards
motor cortex function
top-down control
commands for muscle activation
regulation of spinal cord circuits
UMNs start here
symptoms of motor cortex damage
impaired movement
poor high level coordination
weakness of voluntary movement
UMN syndrome
cerebral palsy - causes and symptoms
causes:
result of damage to motor control structure (often motor cortex) often through pressure on brain
often pre or peri-natally
50% with premature birth
affects UMNs
most common movement disorder in children - 2 in 1000 births
symptoms:
stiffness and weakness of muscles - cannot maintain appropriate level of contraction to muscles - voluntary control
poor coordination
stroke - causes and symptoms (overview)
causes:
interruption of blood supply to cortex (often motor)
UMNs affected
symptoms:
depend on location and severity - usually typical of motor cortex damage
FAST - face arms speech time
two main causes of stroke
cerebral haemorrhage (bleed in brain)
cerebral ischaemia (lack of blood supply to brain)
cerebral haemorrhage
blood is toxic to neural tissue
aneurism - can rupture
if spotted before rupture - can be treated by clipping blood vessel
prevent burst –> low blood pressure, avoid strenuous activity
cerebral ischaemia + cause
interruption of blood supply to part of the brain from blockage of blood vessel
2 causes:
specific “plugs” (thrombus or emboli)
cardiovascular disease (atherosclerosis)
lack of oxygen/glucose leads to excitotoxicity and neuronal cell death
2 areas of damage with cerebral ischaemia + treatment goal
2 areas of damage:
core infarct = irreversibly injured tissue
ischemic penumbra = zone of stunned but salvageable tissue
treatment goal = rescue penumbra by reopening the blocked blood vessel
fine motor control as a symptom of motor cortex damage
prominent and widespread symptom due to homunculus - large representations which are unlikely to be missed by damage
positioning of middle cerebral artery (MCA) in stroke
upper motor neuron syndrome
collection of symptoms from damage to UMNs (in cortex) or their pathways (spinal cord
leads to lack of voluntary control of muscles via LMNs and lack of regulation of LMNs via spinal reflex circuits
reflexes can become abnormal e.g. Babinski reflex (toe movement response - curl in or up and out) from UMN problem
difficulties separating cognitive and motor damage
speech may be impaired without cognition - can make wrong assumptions and act like they have cognitive deficits too, just issues expressing this
basal ganglia - when at rest
CP = rest
GP = tonically active
thalamus = inhibited
motor cortex = reduced excitation of LMNs
basal ganglia - when excited
excitatory input from cortex and DAergic input from SN
CP = transiently excited
GP = transiently inhibited
thalamus = excited (inhibition by GP is stopped)
motor cortex = increased excitation of LMNs
why study genetic causes of idiopathic diseases
if gene mutation is reliably associated with clinical phenotype - can learn about downstream molecular/cellular events responsible for condition overall
clues for drug development to affect certain proteins or other parts of the process
gene therapy to alter faulty genes
i.e. gene -> protein -> cell behaviour -> CNS pathway -> Parkinson’s
diseases and syndromes from disruption to basal ganglia (5)
Huntingdon’s
sudden, jerky, involuntary movements with no purpose
no weakness, ataxia or sensory deficit
Tourette’s
sudden, repetitive, [involuntary] movements or utterances
Tardive Dyskinesia
repetitive, involuntary, purposeless movements
difficulty in stopping movements
Hemiballismus
violent, involuntary movements
(ballistic movements)
Parkinson’s
tremor, slow movement, shuffling, increased muscle tone (rigidity), mask-like expression
Parkinson’s causes and symptoms
causes
10% from gene mutation - 90% idiopathic
old theory = low DA from SN - therefore reduced excitation of LMNs and motor control
new theory = alpha-synuclein and Lewy bodies
motor symptoms
involuntary tremor, slowness of movement, rigidity, shuffling
difficulty initiating voluntary movement
paucity of spontaneous movement (insufficient)
bradykinesia = slow movement
akinesia = no movement
increased muscle tone = rigidity
resting tremor = pill rolling @4-5Hz
shuffling gate, flexed posture, impaired balance
mask-like expression
non-motor symptoms
sleep disorder, depression, anxiety, fatigue, pain, dementia (progresses to worst symptoms with time)
treatment of PD
L-Dopa taken to increase DA levels
treats symptoms not the cause
nigrostriatal neurons continue to degenerate and this isn’t fixed - only will help for a time
only addresses motor symptoms
deep brain stimulation
electrode implanted to block excessive inhibitory output from basal ganglia at globus pallidus - therefore thalamus and motor cortex and LMNs are excited
focussed on motor symptoms
limitations of deep brain stimulation for PD
side effects
not effective for all in the same way
motor symptoms only targeted - can make non-motor worse
often used in later stage of disease - lacks understanding earlier on
alpha-synuclein and Lewy bodies in PD
alpha-synuclein = problematic protein
misfolding of this protein -> oligomers -> fibrils (beta pleated sheet) -> Lewy bodies
Lewy bodies = aggregation of proteins
causes:
* oxidative stress
* disruption of axonal transport
* mitochondrial dysfunction
* synaptic dysfunction
* protein sequestration (aggregation)
* inhibition of ubiquitin/proteosome system (regulation of biological processes)
Lewy bodies develop throughout brain
would explain non-motor symptoms
DA neurons in SN may be more vulnerable
BRAAK stages
used to classify level of disease as it is degenerative (also used for Alzheimer’s)
stages of disturbances to brain areas as it spreads throughout brain from brain stem via olfactory bulb
stages:
1&2 = autonomic and olfactory
3&4 = sleep and motor
5&6 = emotional and cognitive
cerebellar dysfunction symptoms
- impaired movement (ataxia)
- disturbances of posture or gait
- voluntary movement loses fluidity and is mechanical and slow
- intention tremor (not like PD resting tremor - occurs during movement)
- dysarthria = disruption of fine control of speech - slurring
cerebellum damage - ataxia
impaired movement - collection of disorders unified by symptoms with different causes
categorised by symptom, cause, or detailed diagnosis
MND
motor neuron disease
motor neuron degeneration and muscle wasting
degenerative, progressive, and incurable
idiopathic (10% genetic cases)
types of MND and symptoms
ALS (amyotrophic lateral sclerosis) is the most common subtype of MND (75%)
subtypes based on effects on UMNs or LMNs (or both) - ALS affects both - all motor neurons
often altered cognitive function (usually mild), ability to communicate, and affective changes
treatment types for MND
identification of biomarkers for early diagnosis
risk factors
neuroprotective drugs
gene therapies
drugs to slow progression
Sheffield research into biomarkers, gene mutations and drugs to target this
