Movement disorders Flashcards
What are movement disorders
group of nervous system diseases mainly manifested by motor symptoms such as voluntary movement delay, involuntary movement, abnormal muscle tone, postural and gait disorders, and mostly related to basal nucleus or basal ganglia lesions
What is the basal nucleus
is a group of grey matter nuclei in the subcortex, composed of caudate nucleus, putamen, globus pallidus, subthalamic nucleus and substantia nigra.
In higher animals, the basal nucleus regulates motor functions; mainly through the connections between the cerebral cortex- basal nucleus- thalamus- cerebral cortex or cortio-basal ganglia-thalamo-cortical loop
Provide a description of the basal ganglia
consists of 5 pairs of nuclei: caudate nucleus, putamen, globus pallidus, subthalamic nucleus and substantia nigra
What is the striatum
Part of basal ganglia
- consists of dorsal striatum: caudate nucleus
and ventricular striatum: nucleus accumbens and olfactory tubercle
What is the globus pallidus
- part of basal ganglia
consists of an internal segement (GPi) and external segment (GPe)
What is the substantia nigra
- part of basal ganglia
Striatal dopaminergic pathological changes in pathway will lead to increased output of basal nucleus and excessive inhibition of cortical motor function, resulting in parkinsonism, which is mainly characterised by rigidity and hypokinesia
What can striatum and subthalamic nucleus lesions lead to
lead to decreased output of basal nucleus and excessively facilitated cortical motor function, leading to chorea as main manifestation
What is done during surgical treatment of parkinsons disease
One side of subthalamic nucleus of medial globua pallidus is damaged –> applying high frequency electrical stimulation to these two nuclei can alleviate contralaateral symptoms of parkinsons disease which may be to correct abnormal output of basal nucleus
What are the main mainfestations of parkinsonism disease
resting tremors, rigidity, bradykinesia and postural instability
What is the etiology and pathogenesis of parkinsons disease
degeneration and death of substantia nigra dopaminergic neuron
(multi-factorial)
Which genes are associated with PD
Familial cases: LRRK2, PARK7, PINK1, PRKN, or SNCA gene
For the pathology of PD, what basic lesions can be seen
- dopaminergic neurons and other pigment containing neurons in the substantia nigra compact area are degenerated and lost
- loss of pigmentation in substantia nigra is contrasted with a normal midbrain that still has dark pigmentation in the region of the substantia nigra above the cerebral peduncles
- eosinophilic inclusion bodies appear in cytoplasm of remaining neurons –> Lewy bodies
For pathology PD, what biochemical changes can be seen
- due to significant degeneration and loss of strong dopaminergic neurons in patient with PD, substantia nigra striatal dopaminergic pathway changes
- levels of dopamine transmitters in striatum is significantly reduced
- <70-80%: clinical symptoms of dopamine transmitter decrease will appear
- the functions of 2 major transmitter systems, dopamine and ACh in striatum oppose each other, and the balance between the two plays an important role in regulating the motor function of basal nucleus
- striatal dopamine levels are significanlty reduced –> hyperactive ACh system, this transmitter imbalance is closely related to disturbance of cortical basal nucleus thalamus-cortical circuit, the increase in muscle tone and the reduction of movement
- the significant reduction of dopamine levels in the midbrain limbic system and midbrain cortex system is biochemical basis of high-level neural activity abnormailities such as mental decline and mood disorders
What are the clinical manifestations of PD
average age of onset is about 55 years old. it is more common after 60 years of age, before the age of 40 is relatively rare for men to have isidious onset and slow progress
Motor symptoms:
- static tremor
- rigidity
- bradykinesia
- postural instability
Non-motor symptoms:
- cognitive dysfunction and dementia
- psychosis and hallucinations
- sleep disturbances
- fatugue
- autonomic/olfactory/GI dysfunction
- pain and sensory disturbances
Ancillary tests for PD
- routine examinations of blood, salvia and brain fluid are normal
- structural images such as CT and MRI have no characteristuc changes
- molecular imaging PET or SPECT can show abnormalities in early stage of disease or even in subclinical stage and has a high diagnostic value. Dopamine transporter function imaging can also show a significant decrease
How is PD diagnosed
- based on distinctive clinical feature discerned from history and neurologic examination (bradykinesia plus temor/rigidity must be present)
Differential diagnosis for PD
- essential tremor
- dementia with Lewy bodies
- multiple system atropy
- cortico-basal degeneration
- progressive supranuclear palsy
- huntington disease
- secondary parkinsonism
What are the 4 main anti-parkinson drugs used for treatment of PD
- Monoamine oxidase type B (MAO B) inhibitors
- Amantadine
- Dopamine agonists (Das)
- Levadopa
- Anti-cholinergic drugs have some anti-tremor activity
