Movement Disorders

Front 1

parts of the substantia nigra

Back 1

pars reticularis --> outer column
pars compacta --> inner column

substantia nigra is located in the midbrain dorsal to cerebral peduncles and anterior to red nucleus

Front 2

striatum

Back 2

caudate and putamen

Front 3

lenticular nucleus

Back 3

globus pallidus and putamen

Front 4

major inputs to striatum

Back 4

from:

1. all areas of the cortex --> excitatory/glutamate neurons
2. intralaminar nucleus of the thalamus
3. SNc --> dopaminergic neurons enhance direct and indirect pathways via D1 and D2 receptors respectively.
4. locus cereleus and raphe nucleus

Front 5

major outputs of basal ganglia in general

Back 5

from GPi and SNr to:

1. VA and VL thalamus --> primary motor cortex
2. pedunculopontine nucleus

Front 6

projections of GPi

Back 6

1. VA and VL thalamus
2. pedunculopointine nucleus
3. centromedian thalamic nucleus

Front 7

projections of the SNr

Back 7

1. VA and VL thalamus
2. pedunculopointine nucleus
3. mediodorsal thalamic nucleus and superior coliculi

Front 8

sensorimotor division of striatum

Back 8

starts in all areas of cortex to putamen then back to premotor, primary and summplementary motor cortex

mediates movement

Front 9

associative division of striatum

Back 9

starts in cortex of all lobes, goes to dorsal caudate nucleus then back to the prefrontal cortex

mediates cognition

Front 10

limbic division of striatum

Back 10

starts in hippocampus, amygdala, cigulate cortex, temporal and orbitofrontal cortex

goes to the ventral striatum then out to anterior cigulated cortex and medial orbitofrontal cortex

mediates emotion and motivation

Front 11

functional divisions of the striatum

Back 11

sensorimotor --> mediates motor functions
associative --> mediates cognition
limbic --> mediates emotion and motivation

Front 12

default output of GPi and SNr

Back 12

inhibitory GABA neurons to VL and VA thalamus

Front 13

action of corticostriatal neurons

Back 13

excitatory glutamatergic neurons to striatum

Front 14

inputs to GPi and SNr

Back 14

direct pathway --> from striatum --> GPi/SNr
indirect pathway --> from striatum -->GPe --> STN --> GPi/SNr

Front 15

direct pathway

Back 15

corticostriatal glutamate neurons stimulate striatum
inhibitory GABA neurons in striatum inhibit GPi/SNr (which contains GABAergic neurons)
inhibited GPi/SNr disinhibits VA/VL thalamus (which contains glutamatergic projections)

net effect is thalamocortical stimulation enhanced by SNr via D1

Front 16

indirect pathway

Back 16

corticostriatal glutamate neurons stimulate striatum
GABA neurons in striatum inhibit GPe
inhibited GABA neurons of GPe disnhibits STN
increased glutamate from STN stimulate GPi/SNr leading to inhibition of VA/VL thalamus

net effect is thalamocortical inhibition enhanced by SNr via D2

Front 17

palatal myoclonus

Back 17

...

Front 18

serotonergic centers of the brain

Back 18

dorsal raphe nucleus, hippocampus, cerebellum, spinal cord

Front 19

norepinephrine centers in the brain

Back 19

locus cereleus
lateral tegmentum

Front 20

movement disorder tauopathies

Back 20

PSP
CBD
FTDP-17
Four-repeat tau
ALS-PD

Front 21

movement disorder synucleinopathies

Back 21

PD
DLB
MSA

Front 22

polyQ versus non-polyQ

Back 22

most trinucleotide repeat disorders are CAG repeats

CAG in coding regions --> glutamine (Q) --> polyglutamine or polyQ disorder
CAG in non coding regions --> non-polyQ disorders

Front 23

polyQ movement disorders

Back 23

Huntington
dentatorubral-pallidoluysian atrophy (DRPLA)
several of the spinocerebellar ataxias

Front 24

prevalence of parkinsonian syndromes

Back 24

PD --> 80%

Front 25

non-motor symptoms of PD

Back 25

autonomic --> bloating/constipation, frequency, urgency, impotence, orthostatic hypotension
cognitive --> decreased memory, attention and executive functions; dementia in 30%
psych --> anxiety, depression
sleep --> almost all have sleep disturbances --> REM behavior disorder, RLS, vivid dreams and nightmares, ""sleep attacks""

Front 26

PD red flags -->

Back 26

cognitive impairment within first year --> dementias
symetrical presentation of prominent bulbar signs --> MSA or PSP
early gait disorder with falls --> PSP or vascular disease
wheelchair-bound by 5 years --> PSP or MSA
early autonomic dysfunction --> MSA
severe sleep apnea or onvoluntary sighing --> MSA
apraxia, alien limb or cortical sensory loss --> CBD

Front 27

PD red flags --> cognitive impairment within first year

Back 27

dementias

Front 28

PD red flags --> symetrical presentation of prominent bulbar signs

Back 28

MSA or PSP

Front 29

PD red flags --> early gait disorder with falls

Back 29

PSP or vascular disease

Front 30

PD red flags --> wheelchair-bound by 5 years

Back 30

PSP or MSA

Front 31

PD red flags --> early autonomic dysfunction

Back 31

MSA

Front 32

PD red flags --> severe sleep apnea or onvoluntary sighing

Back 32

MSA

Front 33

PD red flags --> apraxia, alien limb or cortical sensory loss

Back 33

CBD

Front 34

ioflupane

Back 34

DaTscan (PET)

iodine 123 radioisotope with high affinity for presynaptic DAT transporters which are decreased in the striatum in PD

used to differentiate PD from essential tremor

Front 35

Lewy body

Back 35

intracytoplasmic eosinophilic inclusions with halo in pigmented neurons, including SN
stain positive for alpha-synuclein and ubiquitin

Front 36

Lewy neurites

Back 36

tiny projections growing out of alpha-synuclein positive neurons and inclusions

Front 37

epidemiology of PD

Back 37

90-95% idiopathic with 15% having first-degree relatives with PD
5-10% familial with specific mutations, various modes of inheritance, phenotypes and penetrance

Front 38

manifestations of bradykinesia

Back 38

slow small-amplitude movements, progressively worse with repetition

in limbs --> decreased arm-swing, micrographia, lack of dexterity
speech --> hypophonia
swallowing --> dysphagia
gait --> shortened stride length
face --> hypomimia
posture --> stooping or leaning

Front 39

most essential sign for diagnosis of parkinsonism

Back 39

bradykinesia

Front 40

characteristics of parkinsonian tremor

Back 40

asymetric
most noted at rest
increased with mental concentration during tasks

Front 41

characteristics of parkinsonian gait

Back 41

postural instability and gait disturbance (if early in the course --> PSP, MSA)
narrow-based, short stride length, reduced arm swing, slow intiation, turning en-bloc
PSP and MSA have impaired tandem gait and wider-based gait

Front 42

criteria for PD diagnosis

Back 42

1. bradykinesia AND resting tremor, rigidity or postural instability
2. unilateral onset, excellent response to levodopa, levodopa-induced dyskinesia

if early prominent postural instability, dysautonomia, dementia, gaze palsy, neuroleptics or poor response to levodopa --> consider parkinsonian syndromes

Front 43

classic PSP presentation

Back 43

usually starts with postural instability with falls
visual and speech difficulties
apathy
decreased vertical sacades with square-wave jerks
no significant dysautonomia

Front 44

PSP MRI

Back 44

midbrain atrophy
humingbird sign

Front 45

eyelid apraxia

Back 45

PSP-parkinsonian variant
treat with botox

Front 46

variants of PSP

Back 46

PSP Richardson syndrome (classic)
PSP-parkinsonism
PSP-pure akinesia with gait freezing
PSP-CBS
PSP-FTD

Front 47

signs of dysautonomia in MSA

Back 47

urinary urgency
constipation
orthostatic hypotension
erectile dysfunction

Front 48

parkinsonism in MSA

Back 48

parkinsonian features usually become prominent after onset of dysautonomia
usually symetrical parkinsonism
gait may be parkinsonian (narrow) or cerebellar (wide-based)
stimulus-induced myoclonus is more common than resting tremor

Front 49

MSA MRI

Back 49

putamen hyperintense external rim and hypodensity
pontine atrophy in sagital view
hot bun cross sign

Front 50

MSA response to levodopa

Back 50

30% of MSA responds to levodopa and get dyskinesias

Front 51

presentation of corticobasal syndrome

Back 51

asymetric progressive ideomotor apraxia staring in the hand and progressing to leg
associated with rigidity, myoclonus and dystonia
alien limb phenomenon --> involuntary grasping, purposeless movements and levitation of affected arm

overlaps with AD, PSP and FTD

Front 52

MSA pathology

Back 52

neuronal loss and gliosis in striatum, SN, LC, inferior olive, pontine nuclei, intermediolateral cell column, onuf nucleus

depletion of cholinergic neuron in PPN and laterodorsal tegmental nucleus

alpha synuclein inclussions are in glia cells throughout

Front 53

HD genetic testing

Back 53

CAG repeat expansion > 37 is pathogenic
discouraged in asymptomatic patients
genetic counseling before and after testing are recommended

Front 54

HD pathology

Back 54

neuronal loss and gliosis in striatum seen with GFAP stain
mostly affects GABAergic medium spiny neurons of striatum predominately in indirect pathway
it also affects other areas of the cortex and brainstem nuclei

Front 55

types of tremor

Back 55

rest tremor --> at rest
postural tremor --> when arms are held up
kinetic tremor --> during movement, specially towards the end of movement
intention tremor --> also a kinetic tremor but implies cerebellar dysfunction
rubral tremor --> at rest, worse with posture and even worse with movement and intention

Front 56

differential diagnosis of rest tremor

Back 56

PD
medication-induced
MSA
vascular parkinsonism
SCA 2 and 3
essential and dystonic tremors can have rest component

Front 57

essential tremor characteristics

Back 57

bilateral symetrical postural and kinetic tremor of hands, forearms and/or head

Front 58

differential diagnosis of postural tremor

Back 58

enhanced physiologic tremor
essential tremor
dystonic tremor
medications
metabolic derangements
neuropathy
PD may have a postural component

Front 59

dystonic tremor

Back 59

associated with the body part affected by dystonia or a different body part
usually jerky tremor, position-specific and sometimes task specific

Front 60

rubral tremor lesion

Back 60

midbrain tegmentum, specially superior cerebellar peduncle

Front 61

physiologic myoclonic jerks

Back 61

hiccups
sneezing
hypnic jerks

Front 62

things to evaluate in myoclonus

Back 62

progressive Vs. nonprogressive
at rest Vs. on action
spontaneous Vs. sensory stimulation
segmental Vs. generalized

Front 63

myoclonus-dystonia presentation

Back 63

myoclonus in the upper trunks and proximal arms associated with or without mild cervical dystonia or writter's cramp

Front 64

myoclonus-dystonia genetics

Back 64

autosomal dominant with complete paternal penetrance and 15% maternal penetrance
DYT11 --> chr 7; SGCE gene
DYT15 --> chr 18; unknown gene

Front 65

orthostatic myoclonus etiology

Back 65

PD
MSA
dementias

Front 66

Lance-Adams syndrome

Back 66

posthypoxic myoclonus
subcortical myoclonus in survivors of cardiorespiratory arrest
specially following respiratory dysfunction and hypercapnia as in asthma

Front 67

what is opsoclonus

Back 67

chaotic myoclonic eye movements

Front 68

opsoclonus-myoclonus ataxia syndrome in children

Back 68

opsoclonus with multifocal myoclonus and truncal/appendicular ataxia
usually paraneoplastic in setting of neuroblastoma or ganglioneuroblastoma

Front 69

opsoclonus-myoclonus ataxia syndrome in adults

Back 69

usually postinfectious or autoimmune; less commonly paraneoplastic from anti-Hu or anti-Ri
associated autoimmune antibodies include anti-Gad, anti-NMDA, anti-gliadin, antiendomysial
autoantibodies bind cerebellar Purkinje and granular cells

Front 70

progressive myoclonic encephalopathies

Back 70

Unverritch disease (Baltic myoclonus)
Ramsay-Hunt syndrome (mediterranean myoclonus)
Sialidosis (cherry-red spot myoclonus)
Neuronal ceroid lipofuscinosis
Myoclonic epilepsy with ragged red fibers (MERRF)
Loafer body disease
Gaucher disease type 3
Krabbe disease

Front 71

pure myoclonic encephalopathies

Back 71

Infantile myoclonic encephalopathy (Ohtahara syndrome)
Severe myoclonic epilepsy of infancy (Dravet syndrome)
Myoclonic astatic epilepsy (Doose syndrome)
West syndrome
Lennox-Gastaut syndrome
Ladau-Kleffner syndrome
Rasmussen syndrome

Front 72

non-progressive myoclonic epilepsies

Back 72

Benign rolandic epilepsy (Benign epilepsy of childhood with centrotemporal spikes (BECTS)
JME
Myoclonic absence seizures

Front 73

hyperekplexia

Back 73

autosomal dominant presents mostly with hypertonia in infants (stiff baby)
tonic spasms and nocturnal myoclonus during first year of life
non-habituating startle responses to brief stimulation during wakefulness is hallmark

Front 74

drugs that improve cortical myoclonus

Back 74

levetiracetam
valproate
clonazepam

Front 75

drugs that worsen cortical myoclonus

Back 75

phenytoin
carbamazepine
lamotrigine

Front 76

cerebellar signs

Back 76

oculomotor disturbances
speech deficits
disturbances in limb movements
deficits of posture and gait
deficits of cognitive operations
subtle autonomic signs

Front 77

afferent ataxia Vs. cerebellar ataxia

Back 77

afferent ataxia relies heavily on visual guidance (Romberg test)
afferent ataxia has no dysarthria and no oculomotor deficits

Front 78

Romberg test

Back 78

closing the eyes causes ataxia of balance
indicates afferent/proprioceptive ataxia
proprioception, vestibular and visual functions are required to maintain balance

Front 79

autosomal dominant ataxias nonmenclature

Back 79

Spinocerebellar Ataxias --> SCA

Front 80

SCAs that have CAG repeat expansion

Back 80

SCAs 1, 2, 3, 6, 7 and 17

Front 81

Only SCA with macular degeneration

Back 81

SCA 7

Front 82

epidemiology of autosomal recessive ataxias

Back 82

Friedreich Ataxia accounts for at least 1/3
20% of cases have an identified molecular defect in over 30 genes
50% remain without a diagnosis

Front 83

genetics of Friedreich ataxia

Back 83

autosomal recessive GAA repeat expansion in an intron of the frataxin (FXN) gene leading to decreased frataxin
frataxin is a mitochondrial protein involved in assembly of iron-sulfur clusters

Front 84

presentation of Friedriech ataxia

Back 84

progressive gait and limb ataxia prior to age 30
absent lower extremity DTRs and plantar extensor responses
dysarthria, oculomotor abnormalities
loss of proprioception and axonal sensory neuropathy
other features include --> diabetes, cardiopathy, scoliosis and pes cavus
cerebellar atrophy is minimal to none

Front 85

x-linked ataxia

Back 85

Fragile X tremor-ataxia syndrome

Front 86

Fragile X tremor-ataxia syndrome

Back 86

affects men over 50 years old
CGG repeat expansion in FMR1 gene on chr X
characterized by ataxia and action tremor
60% have parkinsonism
MRI --> FLAIR hyperintensities in middle cerebral peduncle and periventricular

Front 87

diagnostic criteria for Tourette syndrome

Back 87

motor and vocal tics of onset below age 21 with a duration of at least 1 year

Front 88

Tourette syndrome presentation

Back 88

motor and vocal tics
premonitory sensation
may be suppressed by volition to a variable extent
non-goal directed
worsens with stress and anxiety
usually present between 5-8 years of age

Front 89

dopa-responsive dystonia

Back 89

DYT5, Segawa's disease
more common in females, onset in early childhood
duirnl fluctuations, worse in the afternoons and evenings, may be asymptomatic earlier in the day
dystonia with parkinsonian features
responds to levodopa

Front 90

HD presentation

Back 90

chorea
gait instability
dystonia
neuropsych features --> depression, psychosis, cognitive and executive dysfunction, personality changes

Front 91

primary cervical dystonia

Back 91

begins in adulthood with abnormal head posture, neck pain with or without blepharospasm
treat maily with Botox but also anticholinergics, benzodiazepines, baclofen

Front 92

stereotypies Vs. complex tic

Back 92

sterotypies don't have an premonitory urge with relief after executing tic

Front 93

stiff person syndrome

Back 93

begins in 4th-5th decades
increased axial tone, exagerated lumbar lordosis, stiff abdomen
worsened by startle response and anxiety
anti-GAD antibodies or anti-amphiphysin antibodies
treat with benzos and baclofen

Front 94

ataxia-telangiectasia

Back 94

autosomal recessive mutation of ATM gene leads to impaired DNA repair
presents in childhood with neuropathy, ataxia, opthalmoparesis, telengiectasias in conjunctiva
prone to infections due to hypogamaglobulinemia"