Movement Disorders Flashcards
most likely diagnosis - 65 yo man with 20 yr history of tremor predominantly limited to activities; there is also head tremor. Family history is positive for similar findings and alcohol use decreases its severity
essential tremor
next diagnostic step for essential tremor
MRI of brain and spine
next step in therapy for essential tremor
primidone or propranolol
Froment sign
cogwheel effect when testing muscle tone (esp in arms) without increased tone (rigidity)
cogwheel rigidity
feeling of periodic resistance to passive movement felt by the examiner in a limb
bradykinesia
slowed ability to start and continue movements; impaired ability to adjust the body’s position
lead pipe rigidity
hypertonicity felt in parkinsonian limb throughout the range of movements of a joint; indicative of increased tone in all sets of muscles around a joint
physiological tremor
very low amplitude, fine tremor (bw 6-12 Hz) that is barely visible to naked eye; present in every normal individual when maintaining a posture or movement
main CF of essential tremor
- bilateral tremor of upper extremities (usually)
- begins in mid-late life
- postural and kinetic
- may have mild impairment of balance
resting tremor
occurs when body part is at complete rest against gravity, seen in PD
intention/terminal tremor
marked increase in tremor amplitude during a terminal portion of targeted movement i.e. MS, cerebellar disease
40 yo man in seen in ER for inappropriate behavior and confusion; he has appeared fidgety for recent years and recently, has developed jerky movements of entire body. He is alert, easily distracted and tangential. His balance is slightly altered. He has bilaterally increased reflexes and bilateral ankle clonus - most likely dx?
Huntington’s disease
next diagnostic step for Huntington’s?
genetic counselling and genetic testing for the disease
distal hand movements and long history of fidgeting are typical for…
Huntington disease
chorea
sudden jerky irregular movements with muscle contractions that are not repetitive or rhythmic but flow from one muscle to the next
athetosis
writhing and twisting movements often assoc. with chorea
dystonia
sustained muscle contractions causing twisting and repetitive movements or abnormal posture
tardive dyskinesia
caused by long term or high dose use of typical antipsychotics; impairment of voluntary movements that is irreversible
young child comes in with symptoms resembling parkinsonism, namely bradykinesia, rigidity, dystonia, myoclonus and seizures - what should you consider?
Westphal variant of Huntington’s dz with childhood onset
a young patient comes in with involuntary movements that gradually become more severe, affect all motor activities including gait, arm movements and speech; the patient has symptoms resembling rheumatic fever - dx?
syndenham chorea
21 yr old man with history of progressive dystonia beginning in left UE and spreading his back and left LE; his abnormal movements are complex, involving dystonia, myoclonus and tremor that limit his gait, posture and extremity use - dx?
primary generalized dystonia - DYT1
next diagnostic step for primary generalized dystonia
MRI of brain
next step in therapy for primary generalized dystonia
deep brain stimulation of globus pallidus, pars interna
dystonia
syndrome characterized by sustained muscle contractions, which provokes twisting and repetitive movements or abnormal postures
myoclonus
sudden, involuntary jerking of a muscle or group of muscles
primary dystonia
condition with no etiology that can be identified and dystonia is the sole/major symptom
secondary dystonia
dystonia in the context of a neurological disease in which dystonia is only one of several symptoms or in which dystonia is the result of an environmental insult
clues that dystonia is secondary
- history of trauma, drugs, infections
- dystonia at rest
- atypical site for age of onset
- early onset speech abnormality
- hemidystonia
- abnormal brain imaging or lab tests
which areas of the brain are through to be affected in primary dystonias
low or generally abnormal patterns of activity of basal ganglia output structures: internal segment of globus pallidus and substantia nigra pars reticulata
pharmacologic tx. of dystonia
levodopa
blockers of central muscarinic cholinergic receptors
benzodiazepines
baclofen
middle aged man presents with asymmetric onset of tremor at rest; he has mild poverty of movement (akinesia of face and body) and increased tone - dx?
Parkinson’s
next step in diagnosis of suspected Parkinson’s
MRI of brain to evaluate other disorders in ddx
next step in therapy in newly diagnosed Parkinsons
either DA agonist or MAO-B inhibitor
substantia nigra
consists of pars compacta, pars reticulata and pars lateralis
Lewy body
eosinophilic, round inclusion found in cell cytoplasm of substantia nigra, nucleus basalis of Meynert, locus ceruleus, dorsal raphe and dorsal motor nucleus of CN X; made of alpha-synuclein
multiple system atrophy (MSA) - type P
resembles parkinson’s except that tremor is less prominent and disorder is symmetric
pt presents with symptoms of parkinsonism, but they also have autonomic insufficiency, notably orthostatic hypotension and impotence – what dx. should you be considering?
multiple system atrophy
pt presents with early onset dementia, delusions, hallucinations, fluctuations in consciousness, myoclonus and signs of parkinsonism - dx/
Lewy body dementia
unilateral, coarse tremor, rigidity, increased reflexes as well as limb apraxia, limb dystonia and alien limb phenomenon; asymmetric appearance
corticobasalganglionic degeneration
progressive supranuclear gaze palsy
supranuclear downgaze palsy (inability to voluntarily look down) and square wave jerks on extraocular motion testing; upright rather than flexed posture and frequent falls early on; presence of pseudobulbar emotionality
ataxia
unsteady, clumsy motion of limbs or torso caused by a failure of gross coordination of muscle movements
AD cerebellar ataxia - I
cerebellar ataxia assoc. with additional features related to optic nerve extrapyramidal system, cerebral cortex and peripheral nerves
AD cerebellar ataxia - II
assoc. with pigmentary macular dystrophy
AD cerebellar ataxia - III
pure late onset cerebellar syndrome
dx. of spinocerebellar ataxia
DNA testing
dz. with ataxia, dysarthria, pyramidal signs, peripheral neuropathy, hyperreflexia, cognitive impairment, nystagmus, hypermetric saccades, opthalmoparesis
SCA type 1
dz. with ataxia, dysarthria, peripheral neuropathy, hyporeflexia, dementia and myoclonus, slow saccades and opthalmoplegia
SCA type 2
dz with ataxia, dysarthria, spasticity, parkinsonism, amyotrophy, lid retraction, nystagmus, saccade dysmetria, square wave jerks and opthalmoparesis
SCA type 3
dz with ataxia, dysathria, nystamus (down beating) and saccadic pursuit with very slow progression and lack of family history
SCA type 6
dz with ataxia, dysarthria, retinopathy, peripheral neuropathy, pyramidal signs, infantile phenotypes, saccadic smooth pursuit and slow saccades
SCA type 7
dz with ataxia, dysarthria, mild sensory neuropathy, nystagmus and saccidic pursuit
SCA type 8
pt presents with pure cerebellar ataxia, familial parkinsonism, hereditary spastic paraplegia, hereditary neuropathy and restless legs sydnrome; impaired temperature distinction in all limbs, even trunk and face - dx?
SCA type 3 (i.e. Machado-Joseph syndrome)
radiological feature of SCA
high T2 signal in cerebellar cortex
radiological features of multiple system atrophy (MSA)
high signal lateral to striatum and high signal hot cross bun sign in brainstem
MCC of tardive dyskinesia
chronic exposure to central DA antagonists ex. neuroleptics, metoclopramide
risk factors for developing tardive dyskinesia
advanced age
female
co-existent brain damage
tx. of tardive dyskinesia
benzodiazepines
baclofen
vit. E
tetrabenazine (not in USA)
arching spasms of back and neck are characteristic for…
tardive dyskinesia (vs. dystonia which occurs in segmental form involving muscles of face and neck)
what type of drugs often make tardive dyskinesia symptoms worse?
anticholinergics (which help dystonia)
what time period must elapse for it to be considered tardive dyskinesia?
3 months (vs. dystonia is usually quicker)
what kinds of drugs MC cause tardive dyskinesia?
DA- receptor antagonists i.e. neuroleptics (DA depleting agents such as reserpine or tetrabenazine that do not block R. have not been shown to cause TD)
what structures make up the basal ganglia
caudate nucleus putamen globus pallidus substantia nigra subthalamus
cardinal features of PD
tremor (resting)
rigidity (cogwheel)
akinesia/bradykinesia
postural instability
does PD target men or women?
Men = Women
CF of tremor in PD
rhythmical tremor (slow, 4-6 Hz) that is most prominent with limb at rest, affects distal arm more and is worse with anxiety or excitement as well as walking with arm hanging by side
rigidity in PD
increased resistance to passive movement; first evident in neck and shoulders
- pt perceives it as stiffness and sense of effort to move limbs
bradykinesia in PD
decreased spontaneous and automatic movements with hypomimia, decreased blinking and impaired fine motor movements
postural instability in PD
stooped posture, impaired righting reflexes and festinating gait
atypical sx of PD that should point you to alternate dx
- early onset or rapidly progressing dementia
- rapidly progressive course
- supranuclear gaze palsy
- UMN or cerebellar signs
- urinary incontinence
- postural hypotension
- early falls
what drugs can induce Parkinsonism
phenothiazines - metoclopramide
haloperidol & other neuroleptics
reserpine
toxins that can induce parkinsonism
MPTP
carbon monoxide
manganese
when neuronal system degenerative conditions present with Parkinsonism
multiple system atrophy Shy-Drager syndrome progressive supranuclear palsy striato-nigral degeneration olivopontocerebellar atrophy corticobasal ganglionic degeneration
how can you tell MSA from PD?
MSA has less prominent tremor and symmetric, early ANS dysfunction, cerebellar signs, vocal cord paresis and stimulus sensitive myoclonus
features of cortical basal ganglionic degeneration
unilateral coarse tremor with apraxia, unilateral rigidity, cortical sensory impairment, alien limb, increased reflexes and stimulus sensitive myoclonus
progressive supranuclear palsy
limited vertical gaze with inability to look down, axial rigidity and neck extension, impaired reflexes and visual changes lead to early falls
vascular parkinsonism
lower half rigidity with only legs involved and marked gait impairment
pathophys of PD
loss of DA-containing neurons in substantia nigra as well as gliosis and Lewy bodies on microscopic examination
loss of DA-containing neurons in substantia correlates best with what symptom?
bradykinesia (not tremor)
side effects of Levo-dopa
- dose dependent response
- wearing-off of effects within hours
- painful dystonias
- on-off phenomena and freezing
- postural hypotension
- confusions
- hallucinations
how do you eliminate the wearing-off effects of levodopa?
combine with DA agonist or add anticholinergic / COMT inhibitors
ex. of DA agonists used in PD
pramipexole, ropinirole, bromocriptine, pergolide
use of DA agonists in PD
can be started for mild/early PD to delay onset of dyskinesias with levodopa OR can be used in conjunction with Sinemet to smooth out dose response curve
s/e of DA agonists
hallucinations
psychosis
NV
hypotension
what type of drugs are good for tremor-predominant PD
anti-cholinergics
- benztropine
- benzhexol
- diphenhydramine
- trihexyphenidyl
use of anti-cholinergics in PD
- used to decred ease the relative imbalance in Ach-DA activity in striatum; typically used in early stages of dz
side effects of anticholinergics
urinary retention
constipation
confusion
MAO-B inhibitors in PD
selegeline, rasagiline, L-deprenyl
- inhibit enzymes which break down DA
- reduces symptoms in mild forms of PD or in pts on levodopa
what do you do if a patient develops dyskinesias on levodopa?
- decrease dose of levodopa
- add/increase dose of DA agonist
- discontinue selegeline
- add amantadine
- consider surgery
what is amantadine particularly useful for
alleviates levodopa induced dyskinesias
- MOA: blocks NMDA-R
who is a good candidate for deep brain stimulation for PD?
pt with PD without cognitive or psych symptoms who has medically intractable motor fluctuations, intractable tremor and intolerance of medications
which areas are stimulated in deep brain stimulation for PD
thalamus (VL)
globus paladus (internal segment)
subthalamic nucleus
disorder with muscle rigidity, fever, autonomic lability, altered LOC, elevated CK level and leukocytosis
neuroleptic malignant syndrome
Tx of neuroleptic malignant syndrome
d/c drug
antipyretics/rehydration
bromocriptine - bc NMS develops due to chronic DA blockade (tx includes giving DA)
akathisia
subjective desire to be in constant motion and is assoc. with inability to sit or stand still
tx. akathisia
anticholinergics or BB
tardive dyskinesia
MC movement disorder complicating neuroleptic use; includes chewing movements, lip smacking and rolling of tongue inside mouth
- d/c drug immediately
stiff-man syndrome
fluctuating and progressive muscle rigidity with spasms; usually begins with stiffness of axial and trunk muscles with spread to proximal limb muscles; pts develop lumbar hyperlordosis with restricted movements at hips and spine AND paroxysmal painful muscle spasms often provoked by sudden movement or startle
dx of stiff man syndrome
demonstration of continuous motor unit activity w/o evidence of neuromyotonia, pyramidal or extrapyramidal dysfunction or structural spinal cord disease
what abs may be present in stiff man syndrome
anti GAD ab
ampiphysin ab
tx of stiff man syndrome
baclofen, BDZs - antispastic agents
what kind of a tremor is essential tremor
bilateral, postural and kinetic tremor involving mainly the upper extremities; responsive to alcohol
pathology of essential tremor
not known, PET scans show increased activity in thalamus
type of inheritance in essential tremor
autosomal dominant
- but may occur sporadically
DOC for tx of essential tremor
propranolol
- if no response to BB can try primidone (limited by sedation), topiramate or gabapentin
chorea
involuntary, abrupt and irregular movements that flow as if randomly from one body part to another
symptoms that usually accompany chorea
- inability to sustain muscle contraction (motor impersistence) ie. cant hold tongue protruded or inability to maintain tight handgrip
hereditary causes of chorea
Huntingtons
Wilsons dz
Neuroacanthocytosis
drugs that cause chorea
neuroleptics
antiparkinsonian meds
toxins that cause chorea
alcohol, anoxia, CO
metabolic conditions that cause chorea
hyperthyroidism
hyper/hypoglycemia
what vascular lesion can cause chorea
infarction/ hemorrhage of caudate
tx of chorea
haloperidol
ballism
large-amplitude and poorly patterned flinging or flailing movements of limbs (frequently unilateral as in hemiballismus)
what lesion causes hemiballismus
contralateral lesion in caudate, putamen or subthalamic nucleus
Tx of hemiballismus
DA-depleting and blocking agents
- if severe, thalamotomy or pallidotomy
dystonia
sustained muscle contraction leading to repetitive twisting movements or abnormal postures
geste antagoniste
gently touching the affected body part can diminish dystonia
CF of dystonia
- worse with fatigue, stress or emotions, better with relaxation or sleep
- worsens during voluntary mvmt
- usually present only during specific movement at time of onset and progresses to rest
idiopathic torsion dystonia
primary dystonia - broad spectrum disorder including blepharospasm, torticollis, spasmodic dysphonia, writer’s cramp
myoclonus
sudden-lightning like movement produced by abrupt and brief muscle contraction or inhibition
essential myoclonus
nonphysiologic variety that occurs in isolation w/o evidence of other neurologic symptoms and signs; may improve with small quantities of alcohol
tx of myoclonus
clonazepam
valproate
tics
abrupt, stereotyped, coordinated movements or vocalization
PANDAS
pediatric autoimmune neurologic disorders assoc with streptococcal infection
- associated with exacerbation of tics, OCD or both; strep infection triggers an autoantibody response that cross-reacts with components of basal ganglia in susceptible individuals
tx. of Tics
DA antagonists (haloperidol) but due to potent s/e drugs such as clonazepam or clonidine should be tried first
Wilsons dz
AR disorder with mutation of copper-binding protein (Ceruloplasmin) leading to impaired conjugation and entry of copper to biliary excretory pathway
neurologic manifestations of Wilson’s dz
tremor ataxia dysarthria dyskinesia parkinsonism cognitive dysfunction
tx of wilsons dz
traditionally, penicillamine
now: trientine + zinc (less toxic)
dx of wilsons dz
increased serum copper, decreased serum ceruloplasmin
increased 24 hr copper excretion test
Kayser Fliescher rings on eye exam
paroxysmal dyskinesia
rare group of movement disorders characterized by recurrent attacks of hyperkinesias with preserved consciousness
paroxysmal kinesigenic choreoathetosis
episodes of chorea, athetosis or dystonia are triggered by sudden movements and last for seconds to minutes
tx for PKC
carbamazepine
juvenile onset huntingtons
dystonia and parkinsonian features, 90% from affected father
four cardinal symptoms of Huntingtons
- choreoathetosis
- intellectual decline
- behavioral - personality changes, depression, psychosis
- functional decline - dementia
movement problems in Huntingtons
- chorea –> dystonia –> choreoathetosis
- severe dysarthria, recurrent aspirations
- impaired saccades and loss of smooth pursuit (early sign)
what kind of intellectual decline is seen in Huntingtons dz?
impaired memory and performance skills; mostly subcortical features i.e. problems with executive function
what kind of behavioral changes are seen in Huntingtons?
personality changes
depression w/ biologic signs
psychosis with hallucinations, paranoia and thought disorders
Westphal variant of Huntingtons
develops in childhood – looks more like parkinsonism w/ bradykinesia and rigidity; also have dystonia, myoclonus and seizures
- involvement of neostriatum with atrophy of head of caudate/putamen
dx of Huntingtons
best = genetic testing
imaging shows caudate atrophy
PET shows decreased metabolism in basal ganglia
neurochemistry of Huntingtons
decreased GABA transmission
hyperactivity of DA systems
excitotoxic effect of glutamate
tx of movement symptoms in Huntingtons
anti-DA agents i.e. phenothiazines, haloperidol, reserpine
- only transiently effective before bradykinesia develops with LOTS of side effects
