Week Seven - Movement Disorders Flashcards
What are the characteristic features of all movement disorders?
An abnormality of the form and velocity of movements of the body and are often associated with neuropsychological deficits
The term “movement disorder” has become synonymous with what?
The term “movement disorder” has become synonymous with basal ganglia disease and extrapyramidal features.
Why is it unsurprising that movement disorders are also frequently associated with cognitive and neuropsychiatric problems?
because of the extensive cerebral cortical connectivity of basal ganglia structures
Normal motor control requires maturation of what 2 systems?
musculoskeletal and NS
All the voluntary muscles of the body are directly innervated by what?
The motor neurons in the spinal cord and hindbrain.
What is not innervated by the motor neurons in the SC and hindbrain?
The muscles that activate the eye, which are innervated from midbrain nuclei
The control of voluntary movements has three stages, what are they?
Planning, initiation and execution, which are performed by different brain regions
What are alpha-motor neurons responsible for?
The execution of movements.
What brain areas are involved in planning movement?
cortical association areas and BG and cerebellum
What brain areas are involved in actual initiation of movement?
Motor cortex
What area of the brain is responsible for fine tuning movements?
Cerebellum
Movement is involved in a circuit -
The highest level of the hierarchy comprises many regions of the brain, including those associated with?
Memory, emotions and motivation.
The intent to ‘move’ is formed where?
In the highest level of the hierarchy, in the command neurons (typically, pyramidal neurons in the motor cortex).
Movement is involved in a circuit -
What occurs in the middle level?
Information is relayed to the middle level, which is located in the sensorimotor cortex of cerebral cortex, the basal ganglia of the subcortical nuclei, the cerebellum, and the brainstem.
Postures and movements required to perform the task are determined.
Receive input from receptors in the muscles, the joints, the skin, eyes
Creates a motor program, that defines the information required to perform the desired task.
What modulates activity in the middle level?
Feedback loops involving these independent subcortical systems (the cerebellum and the basal ganglia) modulate activity at the brainstem and cortical levels.
What can movement disorders be categorised into?
Akinetic-Rigid: move too little and Hyperkinetic: move too much
What do bradykinesia and hypokinesia refer to? (used interchangeably with akinetic)
Bradykinesia means ‘slow movement’
Hypokinesia refers to poverty of movement, or movements that are smaller in amplitude than that intended.
What term best captures the essence of PD?
Hypokinesia
Which type of movement disorders are harder to diagnose?
Hyperkinetic
What further subtypes have hyperkinetic movements disorders been broken down into?
jerky and non-jerky syndromes.
What do jerky syndromes comprise?
myoclonus, chorea, and tics
What do non-jerky syndromes comprise?
tremor and dystonia.
What is Myoclonus? (j)
Sudden, brief, shock-like involuntary movements which we may all experience on occasion when falling off to sleep.
What is Chorea? (j)
Quick, irregular, semi-purposive, and predominantly distal involuntary movements which can impart a “fidgety” look to the patient.
What are Tics? (j)
Abrupt, jerky, non-rhythmic movements (motor tics) or sounds (vocal tics) that are temporarily suppressible by will power. These movements are preceded by a feeling of discomfort or an urge that is temporarily relieved by the tic.
What are Tremors? (nj)
An involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements.
What is Dystonia? (nj)
An abnormal movement in which a person’s muscles contract uncontrollably. The contraction causes the affected body part to twist involuntarily, resulting in repetitive movements or abnormal postures.
What is PD defined as?
A progressive degenerative disorder of the CNS
What are the major symptoms of PD?
bradykinesia, temor and rigidity
What is the anchor feature of PD?
Bradykinesia
Walking characteristics of those with PD?
Slowed gait and the feet tend to shuffle along the floor as if weighted down
What happens to handwriting in those with PD?
Becomes small and imprecise
What is a resting tremor (symptom of PD)?
Shaking that occurs in relaxed muscles typically in hands.
Results from activation of opposing muscle groups
What is rigidity (symptom of PD)?
Increased muscle tension that feels ratchet-like when resistance is applied.
Repeated movements of arm and leg joints resulting in stiffness and jerkiness
What is Dysarthia?
Weakness in muscles used for speech causing slow speech (normally a late feature)
What is Dysphagia?
Difficulty swallowing
What is the posture like in those with PD?
stooped with flexion of the trunk and is a hallmark feature of PD
What % of those with PD experience dementia?
70-80% (is a late feature)
If dementia occurs early in ‘PD’ patients what do we do?
We usually change diagnosis to ‘dementia with Lewy bodies’
Dementia produces a greater impact on what in people with PD than people with AD and why?
Social and occupational functioning due to the combination of motor and cog impairments
What increases the risk of developing dementia with PD?
increasing age
longer duration of disease
being male
hallucinations
Approx what % of patients have significant depressive symptoms and anxiety with PD?
30-40% depressive
40% anxiety
What are movement disorders primary linked to?
Dopamine deficits
Psychotic symptoms are frequent in what % of people with PD?
up to 50%
What are the 2 principle categories of PD?
Degenerative PD
Symptomatic/Secondary PD
Define Degenerative PD?
Where a variety of sporadic and genetic degenerative diseases cause nigrostriatal neurodegeneration
Define Symptomatic/Secondary D?
Caused by non-degenerative lesions of the same system or other sites of the straitopallidothalamic-cortical motor circuitry
The etiology of both Degenerative PD
Symptomatic/Secondary PD is definable how?
By disorders affecting the nigrostriatal dopamine transmission and/or downstream signalling pathways
What are the 2 types of Degenerative PD? MUST KNOW
Sporadic and genetic
What are the types of
Symptomatic/Secondary PD? MUST KNOW
Infectious toxic drug-induced brain tumours metabolic
What is the BG?
A brain area comprising a distributed set of brain structures in the telencephalon, diencephalon and mesencephalon
What are the forebrain components of the BG?
caudate nucleus, putamen, nucleus accumbens and global pallidus
The globus pallidus is divided into what 2 segments?
internal (medi) and external (lateral)
What are the 2 pathways in the BG that control the fine tuning of voluntary motor activities?
Direct (activation of D1 receptor which stimulates) - motor cortex to striatum to Gpi to thalamus - activation of motor cortex
Indirect (activation of D2 receptor which inhibit) - inhibition of motor cortex - is the breaks
The two BG pathways have what effects?
agonistic net effects
What do the two dopamine receptors bind to?
the striatum and either stimulates or inhibits each pathway, aiming to stimulate the motor cortex
What is the key feature of PD in relation to dopamine receptors, the pathways and Bg etc?
In people with PD the internal segment of the BG is hyper-activity - inhibiting the thalamus and cortex
What is Levodopa?
Most effective symptomatic treatment of PD
Problems with L-DOPA?
- dopa resistant motor symptoms (freezing episodes, speech impairment)
- dopa resistant non-motor signs (autonomic dysfunction, mood/cognitive impairment)
- drug related side effects (psychosis, motor fluctuations)
What are other pharmacological treatments to help with PD?
Dopamine agonists COMT inhibitors MAO-B inhibitors Anticholinergics Amantadine
What is the general idea of dopamine agonists?
To stimulate dopamine receptors directly
Why are COMT inhibitors used and what do they do?
Are used in combination of L-DOPA and work by blocking the action of enzymes that break down l-dopa
What do MAO-B inhibitors do?
They stop the breakdown of dopamine in the break
Why are anticholinergics useful?
They are helpful for tremors and may ease dystonia associated with wearing-off or peak-dose effect of l-dopa
What is Amantadine?
An antiviral drug used for people who may have developed dyskinesias following long-term use of l-dopa
What technique has been developed to treat severe cases of PD?
Deep brain stimulation
How does deep brain stimulation work?
Very thin wire electrodes are inserted through the skull and brain into the subthalamic nucleus or Gpi.
A cable connected to electrode is then threaded to the chest with a pacemaker which is planted under the skin
What can patients do with the pacemaker used in DBS?
During times of extreme tremore, the patient can activate it and it stimulates the subthalamic nucleus immediately stopping tremors
Limitation of DBS?
Bradykinesia and rigidity still often persist
Dangers of DBS?
Invasive and serious risk of infection/haemorrhaging
What is Huntington’s Disease (HD)
A progressive disorder combining chorea with behavioural disturbances and dementia
How is HD transmitted?
Transmitted via an autosomal dominant inheritance pattern.
What is HD caused by?
An abnormally large number of repeats of the nucleotide sequence CAG on chromosome 4.
The effect of the mutated version of the gene in HD is what?
To disrupt the indirect pathway neurons in the striatum, particularly those of the caudate nucleus. Effectively, GABAergic cells in the striatum expressing D2 receptors (indirect pathway) degenerate over time.
Is there a cure/effective treatment for HD?
No
Why does the loss of indirect pathway neurons in the striatum cause the dyskinesias of Huntington’s disease?
With the loss of these neurons, the excitatory effect of the direct pathway is no longer kept in check by the inhibition of the indirect pathway.
Thus, the motor cortex gets too much excitatory input from the thalamus, disrupting its normal functioning and sending involuntary movement commands to the brainstem and spinal cord.
What is the first manifestation of HD?
Chorea - may be the only one for several years
The majority of HD patients exhibit neuropsychiatric AND cognitive disturbances symptoms such as?
dysphoria, agitation, irritability, apathy, and anxiety.
deficit in attention and concentration, memory retrieval, “executive” functions, and psychomotor speed.
What can be used to treat chorea symptoms?
Drugs that suppress dopaminergic activity, such as antipsychotics (eg, risperidone, olanzapine), and dopamine-depleting drugs (e.g., reserpine)
What is Hemiballismus? What does it result from?
Hemiballismus is usually characterised by involuntary flinging motions of the extremities. The movements are often violent and have wide amplitudes of motion.
Hemiballismus results from a unilateral lesion to the subthalamic nucleus.
Involuntary, ballistic movements result from the loss of the excitatory STN projection to the GPi
