10.6 Hypokinetic disorders Flashcards
What area of the cortex is involved with motor function and what is the role of each?
Primary motor cortex: Execution of movements, input from SMA/PMC and basal ganglia
Supplementary motor area: innervates form distal muscle groups directly
Premotor cortex: involved in the design of movements
What is the effect of the direct pathway?
Net effect of excitatory input from the cortex will be excitation of the thalamus which will facilitate movement
What is the effect of the indirect pathway?
Ne effect of excitation of the indirect pathway will be inhibition of the thalamus, resulting in inhibition of movements
How does teh direct pathway work?
Glu from Cx - Striatum
GABA from Striatum - GPi and SNr
GABA from GPi and SNr - thalamus
Glu from thalamus - cortical motor areas
Disinhibition of the thalamus causes Glu to be released and initiation of movement from motor areas
How does teh indirect pathway work
Glu from Cx - Striatum GABA from striatum - GPe GABA from GPe - STN Glu from STB - GPi and SNr GABA from GPi and SNr - Thalamus GABA from thalamus inhibits movements
What are the cardinal parkinson features?
Tremor, rigidity/stiffness, bradykinesia (slow movement), postural instability
What are the other motor features of parkinsons?
Mask like faces Decreased blink rate Hypometric saccased Hypophonia Dysarthria Dysphagia Micographia Gait abnormalaties: shuffling, reduced arm swing, freezing, festination
What are the non motor parkinsons symptoms?
Anosmia (sense of smell) Depression Dementia Psychosis Pain Constipation Fatigue Sleep disturbance
What are the red flags that it is a parkinson mimic?
Symetrical onset Early falls Broad based gait Early cognitive dysfunction Dyspraxia Cortical sensory loss Early severe autonomic dysfunction Cerebellar signs UMN signs Suprnuclear gaze palsy Antecollis Poor response to levodopa Rapid progression
What are the Parkinson mimics?
Secondary parkinsonism: vascular, drugs, normal pressure hydrocephalus, subdural haematoma, repeated head traums
Dementia with Lewy bodies
Corticobasal degeneration
Progressive supranuclear palsy
Multiple systems atrophy
What are the clinical features of vascular parkinsonism and what causes it?
Postural instability
Greater effect on lower body
Pyramidal signs
Early subcortical damage
due to underlying ischaemic cerebrovascular disease
What is the triad of normal pressure hydrocephalus?
Cognitive impairment, incontinence and gait apraxia
What drugs can induce parkinsons?
Typical Antipsychotics: haloperidol, flupenthixol, chlorpromazine
Atypical antipsychotics: Risperidone
Antiemetics: metoclopramide
Avoid these in parkinsons patients
What are the drugs used to treat psychosis in parkinson patients?
Quetiapine and clozapine
What is the presentation of demetia with lewy bodies and what are the core and suggestive features?
Cognitive impairment preceding or early after onset of parkinsonian motor symptoms
Core features: recurrent well formed visual hallucinations
Suggestive features: REM sleep disorder, sensitivity to neuroleptics
What will you see in corticobasal degeneration?
Apraxia Cognitive decline Dystonia/rigidity Myoclonus Alien hand phenomenon Poor response to levodopa
What will you see in progressive supranuclear palsy?
Deficit in downgaze
Frequent falls
Executive dysfunction
Poor response to levodopa
What will you see in multisystem atrophy?
Autonomic dysfunction
Parkinsonian or cerebellar dysfunction
+/- pyramidal signs
Poor response to levodopa
What causes parkinsons disease, when will symptoms occur?
Destruction of the dopaminergic neurons in the substantia nigra, brainstem, olfactory tract and GIT
Symptoms will occur after 60-80% loss
What are the genes involved in PD and what do they encode?
PARK 1 - 16
Encode: SNCA (alpha synuclein), LRRK2 (leucine rich repeat kinase)
What is the pharmacological treatment for parkinsons?
Levodopa Dopamine antagonists COMT inhibitors MAOB inhibitors Amantadine
What is levodopa, what does it do and what is it effective with and wha should you give it with?
Precursor to dopamine which compensates for the loss of dopaminergic neurons
Most effective drug for the motor symptoms - bradykinesia and rigidity (less effective for tremor)
Should be given with peripheral DOPA decarboxylase inhibitor
What are dopamine agonists, when are they preferable, what are the side effects?
Direct agonist at D2 receptors
May be preferable as first line therapy in younger patients
SE: sleepiness, impulse control disorders and hallucinations
What is a COMT inhibitor
Catechol-O-methyltransferase inhibitor - increases the availability of dopamine at the synapse
Given with l-dopa to increase ‘on’ time
What is a MAOB inhibitor?
Monoamine oxidase B inhibitor which acts to increase the availability of dopamine at the synapse
What is the role of amantadine?
Increases dopamine release, blocks cholinergic receptors (NMDA)
mainly used in adjunctive therapy to reduce drug induced dyskinesia
What should you do when there are motor fluctuations?
Add adjunctive medications
Parenteral dopamine agonist
Intstinal levodopa
What are the surgical targets in PD surgery and what symptoms is it effective for?
GPi - interrupts inhibitory input to the thalamus
STN: reduced excitatory input to GPi
What are the clinical findings of stiff person syndrome?
Rock hard muscles in symptomatic regions Hyperlordosi, paraspinal muscle spasm Stiff gait Hyperreflexia Head retraction reflex Autonomic dysfunction
What is the diagnosis of stiff person syndrome?
- Insidious onset of muscular rigidity with difficulty turning or bending, with rigidity most prominent in limbs and axial muscles
- Co-contraction of agonist and antagonist muscles (clinical and electrophysiological)
- Episodic spasms superimposed on the underlying rigidity precipitated by noise, tactile stimuli and emotional upset
- Absence of other neurological or systemic disease that could explain the symptoms
What is the tetrad of neuroleptic malignant syndrome?
Altered mental state
Muscle rigidity
Fever (>38)
Autonomic instability
What is the proposed mechanism for neuroleptic malignant syndrome?
Central dopamine receptor blockade
