Movement disorders Flashcards
Where in the brain is the substantia nigra?
Midbrain
What are the 2 parts of the striatum?
Caudate and Putamen
What is the globus pallidus also known as?
Pallidum
Which parts of the brain are heavily involved in movement disorders and why?
The SN, striatum, pallidum, and subthalamic nuclei
Control movement via thalamo-cortical projections
Affected = movement disorders
Which disease becomes very similar to Lewy Body Dementia later in the disease?
Parkinson’s (eventually it starts to affect the parietal lobe)
What degenerates in PD?
Dopaminergic neurons in the SN degenerate
What does too little dopamine cause?
Hypokinesia (Bradykinetic, akinetic)
Too little movement
What does too much dopamine cause?
Hyperkinetsia (Dyskinetic)
Too much movement
What effect does dopamine replacement have on patient life expectancies?
Dramatically increases the life expectancy
What diseases are treated with dopamine blockers?
Schizophrenia
What are the side effects of dopamine blockers?
Parkinsonian-like symptoms
People used to believe PD wasn’t genetic.
What happened to change that?
1997
An autosomal dominant family with alpha synuclein mutation developed Parkinson
Alpha synuclein was discovered to be a hallmark of PD
Describe the pattern of dopaminergic neuron loss in PD
Progressive and asymmetric
What are the symptoms of PD?
- Stiffness of arm/shoulder
- Tremor
- Handwriting/micrographia
- Repetitive tasks gets slower on repeating
- Generalised slowing down
What are signs of PD?
- Bradykinesia
- Cogwheel rigidity
- Gait disorder
- Rest tremor
What percentage of people with PD have a tremor?
50%
How do you treat PD?
- Explanation of diagnosis, nurse specialist, patient support groups Physiotherapy, occupational therapy, SALT (speech and language therapy)
Drug treatments: L-dopa Dopamine agonist Amantadine COMT inhibitor MAO-B inhibitor
What is the mechanism of action of amantadine?
Not well understood
An increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake
Name 2 L-DOPA drugs
Co-Careldopa and Co-Beneldopa
both have L-DOPA and Carbidopa
Name 3 dopamine agonists
Ropinirolee
Pramipexole
Pergolide
Name a COMT inhibitor
Entacapone
Name 2 MAO-B inhibitors
Rasagaline and Selegeline
What are the non-motor complications of treatment for PD?
- Nausea
- Postural hypotension
- Fatigue
What are the motor complications of PD treament?
- Dyskinesias due to supersensitivity
- On/off fluctuations
- Wearing off
How does Parkinson’s progress?
Starts with motor symptoms, can go to dementia and then cause hallucinations partially due to the treatment
What is Braak’s hypothesis?
Sporadic PD is caused by a pathogen that enters the bodyviathe nasal cavity
This is swallowed and reaches the gut, initiating Lewy pathology (LP) in the nose and the digestive tract
It is suggested that Parkinson’s spreads from the periphery upwards (ascending theory)
Map out ascending progression of PD
SN –> temporal cortex –> frontal and parietal cortices
What are the prodromal symptoms of PD?
Cognitive: Frontal-executive impairment
Affective: Depression, anxiety, decreased novelty seeking
Sleep: REM behaviour disturbance
Autonomic: constipation
Special senses: loss of sense of smell
What causes the prodromal constipation in PD?
Affects neurons in gut and in brainstem that controls the autonomic NS
What are the NINDS criteria for possible symptoms of progressive supranuclear palsy?
Vertical supranuclear gaze palsy (loss of ability to look up and down)
Falls or the tendency to fall in the first year of symptoms
What are useful clues to suggest someone has supranuclear palsy?
Frontalis over-activity
Impaired verbal fluency without bvFTD
Decreased blink rate
Erect posture with ambling gait
Falls with retained postural reflexes
What is seen in the histology of someone with supranuclear palsy?
Tau tangles and tufted astrocytes
What is supranuclear palsy usually misdiagnosed as?
Parkinson’s (it’s actually a parkinson’s plus condition)
What are the diagnostic criteria for multiple system atrophy?
Autonomic failure –> urinary incontinence (ED for men)
Postural hypertension
Poorly L-DOPA responsive parkinsonism or cerebellar syndrome
What is cerebellar syndrome?
Gait ataxia with cerebral dysarthria (difficulty speaking)
Limb ataxia
Cerebellar oculomotor dysfunction
What are clinical features of multiple system atrophy?
Poly-mini-myoclonus
Action tremor
Incontinence
“Strangulated” dysarthria -problem with speech and swallowing
REM sleep behavioural disorders
Postural hypotension - black out when standing up
Cerebellar eye signs
Cranial-cervical dyskinesia/dystonia
Which disorder is identical to multiple system atrophy in the early stages?
PD
What are cerebellar eye sings?
Flutter, lack of coordinationn, instability of gaze, “dancing eyes” etc.
What part of the nervous system does multiple system ataxia affect?
The autonomic nervous system
What is muscle atonia?
It is how your muscles (except for respiratory muscles and eyes) get paralyzed in REM sleep.
What is a possible prodromal symptom of multiple system ataxia?
REM sleep and behavioural disturbances
What can you see in MSA histology?
Synuclein deposits
Especially in glial cells
What are the symptoms of cortico-basal degeneration?
Limb apraxia
Asymmetric stiffness
Dystonia
Action myoclonus
Cortical sensory loss
Eye movement apraxia
Oro-buccal apraxia
(alien limb)
What is cortico-basal degeneration often misdiagnosed as?
PD or stroke
How is cortico-basal degeneration different from PD?
Doesn’t affect the substantia nigra, it affects the cortex
Causes people to have a useless limb
Doesn’t involve memory problems early on
What is the age of onset for corticobasal degeneration?
50 or over
Do MSA, CBD and PSP respond well to L-DOPA?
No, because the down stream receptors/neurons are not there
