Clin Movement D/os; Path Of Movement D/os

Front 1

Basal ganglia: direct pathway

Back 1

1) Cortex
2) + Striatum
3) - GPi/SNr
4) - Thalamus
5) + Cortex

The inhibition of the SNr/GPi complex by the striatum means LESS inhibition of the thalamus, which excites the cortex.

Front 2

Direct pathway output is (excitatory, inhibitory) of the cortex

Back 2

Excitatory (inhibition of inhibition)

Front 3

Basal ganglia: indirect pathway

Back 3

1) Cortex
2) + Striatum
3) - GPe
4) - STN
5) + GPi/SNr
6) - Thalamus
7) + Cortex

The inhibition of the GPe results in LESS inhibition of the STN, which EXCITES the GPi/SNr, that inhibit the thalamus. Results in less excitation (aka inhibition) of cortex.

Front 4

Indirect pathway output is (excitatory, inhibitory) to the cortex

Back 4

Inhibitory.

Front 5

D (1,2) receptors in BG favor the direct pathway.

Back 5

D1 (They're EXCITED by dopamine)

Front 6

D (1,2) receptors in BG favor the indirect pathway.

Back 6

D2 (They're INHIBITED by dopamine)

Front 7

The striatum consists of _________

Back 7

caudate and putamen

Front 8

A principal cerebellar input to the different thalamic nuclei is from _____

Back 8

inferior olives in the pons

Front 9

brief, jerky movements especially of hands and feet

Back 9

chorea

Front 10

writhing, esp of fingers

Back 10

athetosis

Front 11

proximal rapid, flailing movements

Back 11

ballism

Front 12

rapid, isolated jerks

Back 12

myoclonus

Front 13

PD: Cardinal 3 sx

Back 13

Bradykinesia

Rigidity

Rest tremor

Front 14

What genes are implicated in PD?

Back 14

α synuclein

LRKK2

Parkin

Front 15

LRKK2 gene: relation to PD

Back 15

Autosomal dominant inheritance, accounts for 2-3% of PD

Front 16

PD Diagnosis is confirmed/excluded by ____

Back 16

response to levodopa

Front 17

Drug-induced parkinsonism: what drugs?

Back 17

Those that block DA receptors - neuroleptics, metoclopramide

Front 18

Where is deep brain stimulation implanted in PD?

Back 18

in STN or GPi

Front 19

T/F Essential tremor is less common than PD.

Back 19

F. MORE common (up to 5%)

Front 20

Tremor in PD vs essential tremor

Back 20

ET: ACTION/postural tremor
PD: resting

Front 21

In essential tremor, _____ suppresses the tremor

Back 21

Small amounts of alcohol

Front 22

Essential tremor: tx

Back 22

Beta-blockers

Primidone (anti-seizure)

Topiramate

Front 23

Tardive dyskinesia: what meds?

Back 23

neuroleptics (atypical and typical except clozapine and quetiapine), metoclopramide (Reglan)

Front 24

Tardive dyskinesia: which patients at greatest risk?

Back 24

elderly (25-30%)

Front 25

Tardive dyskinesia: treatment

Back 25

occasional remission after d/c drugs, but often worsens

DBS of GPi may be effective

Front 26

Huntingtons: pathophys is trinucleotide repeats of sequence ____

Back 26

CAG

Front 27

HD: Which neurons/brain area most affected?

Back 27

Caudate. Median spiny projection neurons are particularly susceptible

Front 28

HD: symptoms

Back 28

Choreoathetosis

often early personality change with progressive dementia and eventually psychosis

Death in 10-20 years

Front 29

dystonia: defn

Back 29

Prolonged co-contractions of antagonist muscles

Front 30

HD: diagnosis

Back 30

CT or MRI of caudate as well as cortical atrophy.

Genetic screening for CAG expansion.

Front 31

HD with younger onset is (more, less) severe

Back 31

More

Front 32

Dystonias: tx

Back 32

Anticholinergics

Baclofen

Front 33

Baclofen: MOA

Back 33

is a derivative of gamma-aminobutyric acid (GABA). It is primarily used to treat spasticity and is in the early stages of use for the treatment of alcoholism.

Front 34

Lewy body dementia: defn

Back 34

early onset dementia with hallucinations and parkinsonian features.

Front 35

Lewy body dementia: histology

Back 35

cortical lewy bodies

Front 36

What are Lewy bodies made of?

Back 36

α-synuclein eosinophilic inclusions in affected neurons

Front 37

T/F Suicide is common cause of death in HD

Back 37

T

Front 38

Tourette's syndrome: age of onset and gender

Back 38

3-16% children age 13-14 years

males more commonly affected

Front 39

Tourette's: clinical dx features

Back 39

Onset before age 18/21, multiple complex & phonic tics
Motor tics usually begin between ages 3 to 8, many greatly improve by age 19 or 20.

Front 40

Tourette's: when does it usually improve?

Back 40

age 19-20

Front 41

Tourette's: treatment

Back 41

α agonists (guanfacine, clonidine) for milder cases

Neuroleptics for more severe cases

Front 42

tetrabenazine : MOA

Back 42

Vesicular monoamine transporter 2 (VMAT) inhibitor.

Promotes early degradation and reduced concentration of DA (and other monoamines)

Front 43

guanfacine: MOA

Back 43

selective α2A receptor agonist

Front 44

Restless legs syndrome: prevalence and associations

Back 44

~10-12% adults, approaching 20% age > 80 yrs; AD inheritance in a majority (multiple genes identified)

Front 45

Restless legs syndrome: dx criteria

Back 45

1) Urge to move legs
2) Worsens with rest
3) Improves with activity
4) Worse at night

Front 46

Restless legs syndrome: lab workup

Back 46

Check morning fasting serum ferritin; B12; folate

Front 47

Restless legs syndrome: tx

Back 47

D/C SSRI’s, lithium, antihistamines, neuroleptics

<b>Dopamine agonists</b>

Opiates for resistant cases

Front 48

Wilson's disease: inheritance

Back 48

autosomal recessive

Front 49

Wilson's disease: pathophys

Back 49

accumulation of Cu in tissue

Caused by Cu-binding ATPase mutation leads to <b>reduced incorporation of copper into ceruloplasmin and reduced biliary excretion of copper</b>.

Front 50

Wilson's disease: age of onset

Back 50

usually 2nd decade, sometimes 3rd (but reported as late as mid-50s)

Front 51

Wilson's disease: clinical features

Back 51

1) ALWAYS liver involvement

2) Movement problems: tremor, parkinsonism, dystonic, chorea, FIXED GRIMACE

3) Emotional lability, cognitive decline, psychosis may occur

Front 52

Wilson's disease: PE findings

Back 52

<b>Kayser-Fleischer Rings:</b> ring of copper at margin of cornea, present in all with neurological symptoms

Front 53

Wilson's disease: tx

Back 53

1) Reduced dietary Cu
2) Cu-chelating agents
3) Liver transplant is curative in advanced cases with late dx
4) SCREEN RELATIVES

Front 54

PD: macroscopic changes

Back 54

depigmentation of substantia nigra and locus coeruleus

Front 55

PD: microscopic changes

Back 55

Neuronal loss in substantia nigra pars COMPACTA.

Some remaining neurons have cytoplasmic inclusions - Lewy bodies. These are eosinophilic with concentric lamellated pattern.

Front 56

&alpha;-synuclein: relation to PD

Back 56

Mutated in one form of familial autosomal dominant PD

Front 57

Normally an unstructured soluble protein, alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions characterized by ______.

Back 57

Lewy bodies

Front 58

MPTP: defn

Back 58

by-product of illegal drug manufacturing that causes signs and sx of PD in humans and experimental animals. Causes selective damage of DA neurons of SN.

Front 59

Progressive Supranulear Palsy
: defn

Back 59

PD-plus degenerative disease involving the gradual deterioration and death of specific areas of the brain

the basal ganglia, particularly the subthalamic nucleus, substantia nigra and globus pallidus;
the brainstem, particularly the portion of the midbrain where "supranuclear" eye movement resides;
the cerebral cortex, particularly that of the frontal lobes;
the dentate nucleus of the cerebellum;
and the spinal cord, particularly the area where some control of the bladder and bowel resides.

Front 60

Progressive Supranulear Palsy: visual symptoms

Back 60

The visual symptoms are of particular importance in the diagnosis of this disorder. Notably, the ophthalmoparesis experienced by these patients mainly concerns voluntary eye movement. Patients tend to have difficulty looking down (a downgaze palsy) followed by the addition of an upgaze palsy.

Front 61

Multiple System Atrophy
: defn

Back 61

PD plus syndrome characterized by degeneration of multiple systems. Progresses quickly.

Front 62

Multiple System Atrophy
: symptoms

Back 62

autonomic dysfunction
parkinsonism (muscle rigidity +/ tremor and slow movement)
ataxia (Poor coordination / unsteady walking)

Front 63

HD: Pathological changes

Back 63

Atrophy of Caudate nucleus & Putamen
Large lateral ventricles
Severe neuronal loss and astrocytosis in Corpus Striatum
Variable Cortical neuronal loss

Front 64

Wilson's disease: what changes in astrocytes?

Back 64

Large indented nucleus called Alzheimer's type II glia (NOT Alzheimer's neurofibrillary tangles)

Front 65

Subtantia nigra pars compacta projects to striatum via the ____ pathway.

Back 65

Nigrostriatal

Front 66

Loss of dopaminergic tone results in excess of _________ tone

Back 66

cholinergic

Front 67

2 approaches to treating PD

Back 67

1) Increase DA tone
2) Decrease ACh tone

Front 68

Changes of what tone are more effective on bradykinesia and rigidity sx of PD?

Back 68

enhance DA tone