T2 L9 Parkinson's disease Flashcards
What is ballismus?
High amplitude flailing of limbs on one side of the body
What is the pathophysiology of ballismus?
Inhibition of STN so no excitatory signals are produced to GPi so GPi does not inhibit thalamus so thalamus excites cortex
What is the commonest cause of ballismus?
Stroke
What is a tic?
Brief, repetitive stereotypic movements with premonitory urge
What are the types of tics?
Simplex: blinding, coughing
Complex: jumping or twirling
Plus: motor disorder
Coprolalia: swearing
What can help reduce tics?
Distraction & concentration
What can make tics worse?
Anxiety
Fatigue
What is Tourette syndrome?
More severe expression on a spectrum of tic disorders
What other conditions are associated with tics?
50% have ADHD
33.3% have OCD
≥50% have anxiety
What are come causes of tic disorders?
Complex genetic inheritance
Post infectious immune
What is chorea?
Jerky, brief, irregular contractions that aren’t repetitive or rhythmic
Appear to flow from one muscle to the next
Patient appears fidgety / restless
What is the pathophysiology of chorea?
Inhibition of STN –> no excitation signal produced to GPi so no signal to thalamus which causes it to excite cortex
What are some causes of chorea?
Huntington’s disease
Drugs- neuroleptics
What is the genetics of Huntington’s disease?
Trinucleotide repeat on chromosome 4
Autosomal dominant with complete penetrance
Longer the repeat sequence the earlier the disease presents
Normal is 10-28 repeats
Disease is 36-121 repeats.
What is the clinical presentation of Huntington’s disease?
Cognitive - inability to make decisions, multitasking, slowness of thought
Behavioural -irritability, depression, apathy, anxiety, delusions
Physical - chorea, motor persistence, dystonia, eye movements
What is myoclonus?
Brief movement
Rapid onset & offset
Positive or negative
What is the pathophysiology of myoclonus?
Unknown
Possible imbalance between excitatory & inhibitory neurotransmitters as it is treatable with anti epileptic drugs
Perturbations of motor control system leading to brief disequilibrium which explains why it is present at multiple levels
What are the causes of myoclonus?
Juvenile myoclonic epilepsy
Brain hypoxia
Prion disease
What is dystonia?
Abnormal twisting posture associated with jerky tremor
Often axial, facial, trunk
What is the pathophysiology of dystonia?
Unknown
Functional PET studies suggested abnormal activity in motor cortex, supplementary areas, cerebellum & basal ganglia
Abnormal activity in basal ganglia suggested by dystonia being caused by blocking dopamine receptors & some dystonia being levodopa responsive
What are the causes of dystonia?
Stroke Brain injury Encephalitis Parkinson's disease Huntington's disease
What is a tremor?
Involuntary, rhythmic, sinusoidal alternating movements of part of the body
Affect different parts of the body
Different occurrence e.g. rest, postural, kinetic
What is the pathophysiology of a tremor?
Postulated theory is increased activity in cerebothalamocortical circuit
PD: dopamine dysfunction in pallidum
ET: GABAergic dysfunction in cerebellum
What are the types of drug treatment for hyperkinetic movement disorders?
Dopamine (D2) receptor blocking agents
Dopamine depleting agents
Atypical anti-psychotics
What are some examples of dopamine receptor blocking agents?
Haloperidol
Chlorpromazine
Pimozide
Risperidone
What are some examples of dopamine depleting agents?
Tetrabenazine
Reserpine
What are some examples of atypical antipsychotics?
Clozapine
Olanzapine
Aripiprazole
What is an ocylogyric crisis?
Very characteristic acute response to certain drugs
Fixed stare, upward deviation of eyes
Neck extension
Trunk extension
Jaw spasms & possible tongue protrusion
Acute dystonic reaction
What is neuroleptic malignant syndrome?
Acute medical emergency due to D2 blocking drugs Rigidity / muscle breakdown - raised CPK Fever Autonomic instability Confusion
What is Parkinsonism?
Akinetic rigid syndrome
Symptoms: slowness of movement, stiffness, shaking
What are the physical signs of Parkinsonism?
Slowness & poverty of movement
Voluntary movements are harder to initiate
Rigidity
Rest tremor
What are the non-motor signs of Parkinsonism?
Mood - depression, anxiety
Dementia - slowed thought, mental inflexibility
Autonomic involvement - postural hypotension, hyper salivation
Sleep disturbance - restless legs, REM, parasomnia
What are the neurodegenerative causes of Parkinsonism?
Idiopathic - Parkinson’s disease
Diffuse lewy body disease
Atypical parkinsonism
Multiple system atrophy, progressive supra nuclear palsy, corticobasal degeneration
What are the secondary causes of Parkinsonism?
Drugs - haloperidol, MPTP
Cerebrovascular disease
Hydrocephalus
Toxicity / metal deposition disorders
What are the genetic causes of Parkinsonism?
Metabolic - Wilson’s disease
Rare familial causes
What is the pathophysiology of Parkinsonism?
Decreased dopamine input –> reduced activation of direct pathway & reduced inhibition (higher activity) of indirect pathway. This leads to reduced movements.
What is Parkinson’s disease?
Neurodegenerative condition primarily affecting dopaminergic cells of substantial nigra
What is the histological hallmark of Parkinson’s disease?
Lewy bodies
What were some early drug therapies for Parkinson’s disease?
Amatadine - initially anti flu agent. Glutamate agonist
Anticholinergics - procyclidine, benzhexol. Limited by side effects
Mono-amine oxidase inhibitors
What are monoamine oxidase inhibitors?
Prevent breakdown of monoamine chemical transmitters
2 isoforms: MAO-type A (serotonin, adrenaline, noradrenaline, dopamine). MAO-type B (dopamine)
What is non selective MAO-I used for?
Depression (moclobemide)
Rarely used due to problems metabolising dietary amines / tryptophan leading to risk of hypertensive crisis from cheese, red wine & marmite
What is more selective MAO-IB used for?
Parkinson’s disease
Selegiline, rasagiline
No dietary restrictions
What is entacapone / tolcapone used for?
Reduced peripheral metabolism of L-DOPA. Also reduces central but to a lower extent
What are the pros & cons of entacapone / tolcapone?
Pros: increases duration & efficacy of action of L-Dopa
Good for wearing off with L-Dopa inbetween doses
Cons: makes dyskinesia worse, diarrhoea
Liver disease with tolcapone
Where is L-DOPA absorbed?
Duodenum
What affects L-DOPA absorption?
Poor gastric motility / constipation & diet / protein load
What do dopamine agonists do?
Bypass degenerating nigrostriatal neurons
Directly activate dopamine receptors
No need for enzymatic conversion
More stable & longer acting
What are the pros of amorphine?
Very instant effect as given by s/c infusion
Reduces dyskinesia by allowing continuous dopaminergic stimulation
What are the cons of amorphine?
Only for right patients
Skin nodules
What is the favoured target for deep brain stimulation?
Subthalamic nucleus for Parkinson’s disease
Pallidum for dystonia
Thalamus for tremor
What is the future for non-drug therapies?
Neurorestorative (stem cells)
Neuroprotective (growth factors)
