Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
94 Cards in this Set
- Front
- Back
parts of the substantia nigra |
pars reticularis --> outer column |
|
striatum
|
caudate and putamen
|
|
lenticular nucleus
|
globus pallidus and putamen
|
|
major inputs to striatum |
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 |
|
major outputs of basal ganglia in general
|
from GPi and SNr to:
1. VA and VL thalamus --> primary motor cortex 2. pedunculopontine nucleus |
|
projections of GPi
|
1. VA and VL thalamus
2. pedunculopointine nucleus 3. centromedian thalamic nucleus |
|
projections of the SNr
|
1. VA and VL thalamus
2. pedunculopointine nucleus 3. mediodorsal thalamic nucleus and superior coliculi |
|
sensorimotor division of striatum
|
starts in all areas of cortex to putamen then back to premotor, primary and summplementary motor cortex
mediates movement |
|
associative division of striatum
|
starts in cortex of all lobes, goes to dorsal caudate nucleus then back to the prefrontal cortex
mediates cognition |
|
limbic division of striatum
|
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 |
|
functional divisions of the striatum
|
sensorimotor --> mediates motor functions
associative --> mediates cognition limbic --> mediates emotion and motivation |
|
default output of GPi and SNr
|
inhibitory GABA neurons to VL and VA thalamus
|
|
action of corticostriatal neurons
|
excitatory glutamatergic neurons to striatum
|
|
inputs to GPi and SNr |
direct pathway --> from striatum --> GPi/SNr
indirect pathway --> from striatum -->GPe --> STN --> GPi/SNr |
|
direct pathway
|
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 |
|
indirect pathway
|
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 |
|
palatal myoclonus
|
... |
|
serotonergic centers of the brain |
dorsal raphe nucleus, hippocampus, cerebellum, spinal cord |
|
norepinephrine centers in the brain |
locus cereleus |
|
movement disorder tauopathies
|
PSP
CBD FTDP-17 Four-repeat tau ALS-PD |
|
movement disorder synucleinopathies
|
PD
DLB MSA |
|
polyQ versus non-polyQ
|
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 |
|
polyQ movement disorders
|
Huntington
dentatorubral-pallidoluysian atrophy (DRPLA) several of the spinocerebellar ataxias |
|
prevalence of parkinsonian syndromes
|
PD --> 80%
|
|
non-motor symptoms of PD |
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"" |
|
PD red flags -->
|
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 |
|
PD red flags --> cognitive impairment within first year
|
dementias
|
|
PD red flags --> symetrical presentation of prominent bulbar signs |
MSA or PSP
|
|
PD red flags --> early gait disorder with falls |
PSP or vascular disease
|
|
PD red flags --> wheelchair-bound by 5 years |
PSP or MSA
|
|
PD red flags --> early autonomic dysfunction |
MSA
|
|
PD red flags --> severe sleep apnea or onvoluntary sighing |
MSA
|
|
PD red flags --> apraxia, alien limb or cortical sensory loss |
CBD
|
|
ioflupane |
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 |
|
Lewy body
|
intracytoplasmic eosinophilic inclusions with halo in pigmented neurons, including SN
stain positive for alpha-synuclein and ubiquitin |
|
Lewy neurites
|
tiny projections growing out of alpha-synuclein positive neurons and inclusions
|
|
epidemiology of PD |
90-95% idiopathic with 15% having first-degree relatives with PD
5-10% familial with specific mutations, various modes of inheritance, phenotypes and penetrance |
|
manifestations of bradykinesia
|
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 |
|
most essential sign for diagnosis of parkinsonism
|
bradykinesia
|
|
characteristics of parkinsonian tremor |
asymetric
most noted at rest increased with mental concentration during tasks |
|
characteristics of parkinsonian gait
|
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 |
|
criteria for PD diagnosis
|
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 |
|
classic PSP presentation
|
usually starts with postural instability with falls
visual and speech difficulties apathy decreased vertical sacades with square-wave jerks no significant dysautonomia |
|
PSP MRI
|
midbrain atrophy
humingbird sign |
|
eyelid apraxia
|
PSP-parkinsonian variant
treat with botox |
|
variants of PSP
|
PSP Richardson syndrome (classic)
PSP-parkinsonism PSP-pure akinesia with gait freezing PSP-CBS PSP-FTD |
|
signs of dysautonomia in MSA
|
urinary urgency
constipation orthostatic hypotension erectile dysfunction |
|
parkinsonism in MSA
|
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 |
|
MSA MRI
|
putamen hyperintense external rim and hypodensity
pontine atrophy in sagital view hot bun cross sign |
|
MSA response to levodopa
|
30% of MSA responds to levodopa and get dyskinesias
|
|
presentation of corticobasal syndrome |
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 |
|
MSA pathology
|
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 |
|
HD genetic testing
|
CAG repeat expansion > 37 is pathogenic
discouraged in asymptomatic patients genetic counseling before and after testing are recommended |
|
HD pathology
|
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 |
|
types of tremor
|
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 |
|
differential diagnosis of rest tremor
|
PD
medication-induced MSA vascular parkinsonism SCA 2 and 3 essential and dystonic tremors can have rest component |
|
essential tremor characteristics
|
bilateral symetrical postural and kinetic tremor of hands, forearms and/or head
|
|
differential diagnosis of postural tremor |
enhanced physiologic tremor
essential tremor dystonic tremor medications metabolic derangements neuropathy PD may have a postural component |
|
dystonic tremor
|
associated with the body part affected by dystonia or a different body part
usually jerky tremor, position-specific and sometimes task specific |
|
rubral tremor lesion
|
midbrain tegmentum, specially superior cerebellar peduncle
|
|
physiologic myoclonic jerks |
hiccups
sneezing hypnic jerks |
|
things to evaluate in myoclonus
|
progressive Vs. nonprogressive
at rest Vs. on action spontaneous Vs. sensory stimulation segmental Vs. generalized |
|
myoclonus-dystonia presentation
|
myoclonus in the upper trunks and proximal arms associated with or without mild cervical dystonia or writter's cramp
|
|
myoclonus-dystonia genetics |
autosomal dominant with complete paternal penetrance and 15% maternal penetrance
DYT11 --> chr 7; SGCE gene DYT15 --> chr 18; unknown gene |
|
orthostatic myoclonus etiology
|
PD
MSA dementias |
|
Lance-Adams syndrome
|
posthypoxic myoclonus
subcortical myoclonus in survivors of cardiorespiratory arrest specially following respiratory dysfunction and hypercapnia as in asthma |
|
what is opsoclonus
|
chaotic myoclonic eye movements
|
|
opsoclonus-myoclonus ataxia syndrome in children |
opsoclonus with multifocal myoclonus and truncal/appendicular ataxia
usually paraneoplastic in setting of neuroblastoma or ganglioneuroblastoma |
|
opsoclonus-myoclonus ataxia syndrome in adults
|
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 |
|
progressive myoclonic encephalopathies
|
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 |
|
pure myoclonic encephalopathies
|
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 |
|
non-progressive myoclonic epilepsies
|
Benign rolandic epilepsy (Benign epilepsy of childhood with centrotemporal spikes (BECTS)
JME Myoclonic absence seizures |
|
hyperekplexia
|
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 |
|
drugs that improve cortical myoclonus
|
levetiracetam
valproate clonazepam |
|
drugs that worsen cortical myoclonus
|
phenytoin
carbamazepine lamotrigine |
|
cerebellar signs
|
oculomotor disturbances
speech deficits disturbances in limb movements deficits of posture and gait deficits of cognitive operations subtle autonomic signs |
|
afferent ataxia Vs. cerebellar ataxia
|
afferent ataxia relies heavily on visual guidance (Romberg test)
afferent ataxia has no dysarthria and no oculomotor deficits |
|
Romberg test
|
closing the eyes causes ataxia of balance
indicates afferent/proprioceptive ataxia proprioception, vestibular and visual functions are required to maintain balance |
|
autosomal dominant ataxias nonmenclature
|
Spinocerebellar Ataxias --> SCA
|
|
SCAs that have CAG repeat expansion |
SCAs 1, 2, 3, 6, 7 and 17
|
|
Only SCA with macular degeneration |
SCA 7
|
|
epidemiology of autosomal recessive ataxias |
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 |
|
genetics of Friedreich ataxia
|
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 |
|
presentation of Friedriech ataxia
|
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 |
|
x-linked ataxia
|
Fragile X tremor-ataxia syndrome
|
|
Fragile X tremor-ataxia syndrome |
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 |
|
diagnostic criteria for Tourette syndrome
|
motor and vocal tics of onset below age 21 with a duration of at least 1 year
|
|
Tourette syndrome presentation |
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 |
|
dopa-responsive dystonia
|
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 |
|
HD presentation
|
chorea
gait instability dystonia neuropsych features --> depression, psychosis, cognitive and executive dysfunction, personality changes |
|
primary cervical dystonia
|
begins in adulthood with abnormal head posture, neck pain with or without blepharospasm
treat maily with Botox but also anticholinergics, benzodiazepines, baclofen |
|
stereotypies Vs. complex tic
|
sterotypies don't have an premonitory urge with relief after executing tic
|
|
stiff person syndrome |
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 |
|
ataxia-telangiectasia
|
autosomal recessive mutation of ATM gene leads to impaired DNA repair |