Parkinsons Flashcards

Question

How will damage to vestibulocerebellum present?

Answer 1

ataxia, dysequilibrium, nystagmus

Answer 2

distrubances in control of axial and trunk muscles during attempted antigravity postures and scanning speech

Answer 3

delay in inititating movements and decomposition of movements

Answer 4

DR PANISH D D- dysdiadachokinesia (rapidly alternating) R- Romberg's sign (need 2/3 of proprioception, vestibular function and vision)- ataxia and -ve P- past pointing A-Ataxia (lack of volunatry coordination) N- Cerebellar nystagmus I- Intention/action tremor S-Slurred/scanning speech (dysarthria) H-Hypotonia- knee jerk keeps swinging D- Decomposition of movement (difficultly performing actions that involve simultaneous motion at >1 joint)

Answer 5

Abnormal accumulation of presynaptic protein alpha synuclein bound to ubiquitin in the damaged cells- Lewy bodies which displace other cell components

Answer 6

1) Predisposed inductions sites 2) Inclusion bodies begin to appear in portions of the medulla and the pontine tegmentum (raphe nuclei, reticular nucleus and coeruleus complex) 3) midbrain (SNc, amygdala, subnuclei) 4) Cerebral cortex (deficits in responses to emotional stimuli) 5 and 6) extensive stretches of the neocortex

Answer 7

Parkin (ch6, PARK2) alpha synuclein (4, PARK1/4) NURR1 (nuclear receptor related protein (chromosome 2) Leucine-rich repeat kinase 2 (Lrrk2) (12, PARK 8) PINK1

Answer 8

``` Resting tremor Bradykinesia Rigidity Gait disturbance Postural instability Abnormal fixation fo posture (stooping) ```

Answer 9

``` Micrographia Masked facies Reduced eye blink soft voice dyphagia freezing ```

Answer 10

1) Dopaminergic agent trial | 2) MRI, functional neuroimagin, genetic testing,

Answer 11

Goals of treating the mildly symptomatic patient: o Delay disease progression. No medication has been shown to alter disease course. o Refrain from impairing benefit of future therapies. Nonpharmacologic therapy can be the most beneficial measures at the early stage: o Exercise – emphasizing flexibility, balance and mobility. o Cognitive stimulation. o No proven dietary modulators. Intermediate PD – early treatment when QoL begins to be impaired: o Treat symptoms. o Delay disease progression, and refrain from impairing benefit of future therapies. Advanced disease: o Treat symptoms. o Minimize/treat medication side effects. o Delay disease progression.

Answer 12

Levodopa and carbidopa first line, then combine with dopamine agonists, MAO-B inhibitors, COMT inhibitors etc.. o Amantadine = antiviral (interfere with M2 ion channel required for viral particle to become “uncoated” after endocytosis), antiparkinsonian (induce release of DA, NE, weak NMDA receptor antagonist, anticholinergic on nACh R) o Apomorphine = non-selective dopamine agonist (D1-like & D2-like receptors) If that fails then consider surgery and deep brain stimulation

Answer 13

Increase in the number of polyglutamine (CAG) repeats (over 40) in the coding sequence of the huntingtin gene located on the short arm of chromosome 4. Unsure what protein does but fragments of the mutant protein can be toxic (possibly translocating into the nucleus and interfering with transcriptional upregulation of regulatory proteins). Neuronal inclusions may be a protective mechanism

Answer 14

Motor sx: Chorea (brief, semi-directed, irregular movements that are not repetitive or rhythmic) with Parkinsonism and dystonia developing later Psychiatric symptoms: change in behaviour and personality, impulsiveness, aggressive behaviour, depression and paranoid psychosis Cognitive sympotms: Progressive subcortical demential, with disturbed attention, concentration, depression and irrtability

Answer 15

Family history and genetic testing (positive is >40 CAG repeats) MRI and CT only shows visible cerebral atrophy in the advanced stages of the disease- fMRI and PET can show changes in brain activity before onset of physical sx

Answer 16

1) Patient education 2) Symptom management Treatment for chorea: tetrabenazine clonazepam (benzo site on GABA- anticonvulsant and muscle relaxant), Haloperidol (Dopamine D2 receptor antagonist, strong alpha adrenergic blocking effects), reserpine (atypical, highly potent serotonin and dopamine receptor) Rehabilitation therapy

Answer 17

average duration of illness is approx 19 years (mean death ranging from 51-57 years) with most becoming bedridden- death caused by concurrent infection and high suicide rates

Answer 18

Increased release of dopamine from the few surviving dopaminergic neurons or a floddin gof the synapse with dopamine formed elsewhere SE: dyskinesia, On/off effect as well as nausea, anorexia, postural hypotension, psychological effcts

Answer 19

Act directly on dopamine receptors and their use is associated with a lower incidence of the response fluctuation and dyskinesias that occur with LT levodopa therapy. Ergot or non ergot SE: fatigue, somnolence, peripheral oedma, dyskinesias, confusion, impulse control disorders

Answer 20

Inhibition of MAO-B protects dopamine from extraneural degradation, used with levodopa. • Two different MAO-B inhibitors – Selegiline (which is metabolized to amphetamine, causing excitement, anxiety and insomnia) and Rasagiline, which lacks the unwanted effects of Selegiline.

Answer 21

Catecholamine-O-methyltransferase (COMT) inhibitors: Reduce the metabolism of levodopa to 3-O-methyldopa, thereby altering plasma pharmacokinetics of levodopa, leading to more sustained plasma levels and more constant dopaminergic stimulation of the brain. Given in conjunction with levodopa and a decarboxylase inhibitor. Stalevo is the commercial preparation available that combines levodopa, carbidopa and entacapone. Unwanted effects: Dyskinesias, confusion, hypotension, syncope, diarrhoea, hepatotoxicity (with entacapone).