Lecture 22 Flashcards
Describe drug treatments for PD
-drug replacement of dopamine e.g. Levadopa (L-dopa), precurser of dopamine (dopamine cant cross the blood-brain barrier), can be taken orally and absorbed and transmitted into dopamine and taken up by dopanergic receptors in striatum. Dopamine agonists can also be taken, usually a combination of meds.
Decribe problems with drug replacement
-sensitization causes on-off swings
-undermedication= severe PD symptoms
-overmedication= leads to dyskinesias (abnormal movements)
-need to schedule doses (usually wears off around 4 hours), time dosing to keep in optimal range
Challenges:
-need to continue to increase dose as severeity of symptoms increase (ceiling increases)
-overtime dopanergic cells become hypersensitized to L-dopa and exeeds optimal range leading to unwanted symptoms
-Also meds do not address postural instability and falls
Describe how you could help diagnose PD
give a dose of L-dopa and see if symptoms improve
Describe surgical treatment of PD
-surgical removal of basal ganglia nuclei
-for non-tremor dominant symptoms-> gobus palidus (pallidotomy)
-where tremor is dominant symptom-> thalamus (thalamotomy) thought to be related to an overactive thalamus. Dont get benefits of direct pathway bur removing brake from indirect pathway, releasing thalamus so can get excitation on the cortex
Describe problems with surgical treatments
-collateral damage- affects on other areas
-irriversable
Describe deep brain stim for PD
deep brain stimulation: effectively lesion basal ganglia nuceli using magnetic stimulation
-to globus palidus or subthalamic nucelus
-insert electrode implanted in nuceli of these areas connected to pacemaker
-magnetic electrical pusles shut off neurons in area, can be adjusted to get the most benefits
-procesdure performed while patient awake can find best place for electrode
-specific to indirect pathway, removed effect of indirect pathway, taking away just the brake, still get facilitation
Describe other treatments for PD
-replace deteriorated cells in substantia nigra pars compacta with new cells that can produce dopamine
-fetal cell transplants- attempt to see if implanted in brain whether it would grow into dopanergic neurons, no true benefit (placebo)
-stem cells- future hope- from same indivisual naturally replace dopamine
Describe characteristics of huntingtons disease
-degeneration of striatal cells- caudate and putamen
-cells for indirect pathway mostly affected- leads to excessive infleunce of direct pathways, all gas, no brake
-onset 30-50years, symptoms generally dont arise until mid-late audulthood after having kids
-progressive disorder leading to death
-genetic component- no known cure, one parent with gene 50% chance of having, both, 100% chance
Describe anatomical changes with huntingtons disease
-caudate previously forming lateral wall of ventricle, with degenration, lateral ventricle fills space that was taken up by caudate
Describe symptoms of huntingtons disease
-chorea- “dance”- frequent, non-rhythmic, involuntary movements with fluid or jerky quality, at rest and during movement
-dystonia- abnormal, sustained positions of the limbs, trunk, face
-abnormal eye movements- impaired smooth pursuits, saccades are slow and hard to initiate, optokinetic reflex impaired
-dementia
-emotional- depression, axiety, OCD
Describe treatments for huntingtons
-antidopaminergic medication- remove excessive effecrt, blocking recptors to dopamine
-lesion-thalamotomy, area receiveing direct pathway info
-deep brain stimulation e.g. globus pallidus internus
Describe the movement disorder continuum
-one one end have slow hypokinetic movements (too much brake): bradykinesia, hypokinesia, rigidity
-middle region movements such as dystonia, athetosis, chorea associated with huntingtons
-other end have fast, hyperkinetic movement: ballismus, tics, myoclonus, tremor (slow or fast)
Describe athetosis
-between dystonia and chorea on continuum
-involuntary movements that are slow, with intermittent periods of dystonia
-often involves distal limbs e.g. hands
-transitions of disconnect movments and dystonia
-associated with stroke, affect blood supply to parts of the basal ganglia
Describe hemiballismus
-between chorea and ticks
-fast rapid unwanted movements of limbs, purposeless violent flinging
-caused by vascular lesion to subthalamic nucelus, part of indirect pathway, removes infleunce of subthalamic pathway on internus
-can use neuroleptics- dopamine blockers however longterm may promote parkinsonisms
Describe tourettes syndrome
-onset in early childhood (3-9 years) worsens through teen yeras typically reduced by adulthood (10-15% continue into adulthood)
-4:1 ratio male to female
-genetic component
-affects striatal cells/receptors: dopamine once released typically have reuptake, with tourettes poor reabsorption excessive dopamine available and hypersensitivity of receptors in striatum- overactive direct pathway
-co-morbidities: ADHD, OCD
Symptoms of tourettes
-involuntary motor and vocal tics (non-purposefull, sudden, repetitive, non-rhythmic movements and vocalisations): can be simple or complex:
-simple: motor ticks associated with a simple muscel group or joint e..g blinking, grimasing; vocal ticks chirps simple vocalisations
-complex: motor ticks such as jumping, twisting; vocalisations include formulation of words and sentences, Coprolalia (using curse words etc), ecololia (repeating words back)
-symptoms vary with stress/concentration: increased stress increased need to tick, bring attention to tick, also increase likelihood
Descibe treatments of tourettes
-no cure
-psychotherapy
-dopamine blockers (neuroleptics)
-deep brain stimulation for people with ongoing ticks
Describe a common coping strategy for people with tourettes
-effect of music: listening, producing, performning music
