Movement Disorders Flashcards
Most cases of idiopathic Parkinson Disease are sporadic, but what are some genes that have been associated with familial forms?
SNCA (alpha-synuclein) PARK2 (E3 ubiquitin ligase) UCHL1 (ubiquitin carbosyterminal esterase L1) PINK1 (PTEN-induced putative kinase 1) LRRK2 (leucine-rich repeat kinase 2)
Where is the typical location for dopaminergic neuronal loss in PD?
the substantia nigra pars compacta
(but also the dorsal motor nucleus of the vagus nerve, anterior olfactory structures, locus coeruleus, and temporal mesocortex)
What are the four cardinal features of PD?
tremor
rigidity
bradykinesia
postural instability
Describe the tremor seen in PD?
slow (3-5 hz) and most prominent when the limb is at rest
affects the distal arm more often than the leg, described as a pill-rolling tremor
can also affect the lips, chin and tongue
What percentage of patients with PD will develop dementia as the disease progresses?
25-30%
Why do we give L-dopa and not just dopamine?
dopamine can’t cross the BBB
WHy do we give it with carbidopa?
carbidopa is a peripheral decarboxylase inhibitor that prevents the peripheral conversion of L-dopa to dopamine, thus assuring delivery of adequate drug to the CNS while reducing the incidence of peripheral dopaminergic side effects like nausea, vomiting and hypertension
What has been the proposed strategy for early therapy that will reduce the subsequent risk of dopa-induced dyskinesias?
using dopaminergic agonists like ropinirole
What medication can be helpful for early treatment of the bradykinesia, rigidity and gait disturbance?
amantadine
What are the characteristics of Neuroleptic Malignant Syndrome?
muscle rigidity, fever, autonomic lability, altered LOC, elevated CK, and leukcytosis
What is the treatment for NMS?
discontinue the offending drug
antipyretics
rehydration
bromocriptine or dantrolene
The propensity of a drug to causing tardive dyskinesia is related to its blocking activity at what receptor?
D2
Describe the typical presentation of stiff man syndrome.
stiffness of the axial and trunk muscles, with spread to the proximal limb muscles over time
patients develop a lumbar hyperlordosis with restricted movements of the hips and spine
patients often develop paroxysmal painful muscle spasms, often provoked by sudden movement or startle
What antibodies may be present in stiff man syndrome?
glutamic acid decarboxylase (GAD) antibodies
amphiphysin antibodies
What is the treatment for stiff man syndrome?
benzodiazepines and baclofen
What kind of tremor is seen in essential tremor?
postural tremor only - almost always affecting the hands, but may also affect the head, face, voice, trunk or legs; almost always bilateral
Action or intention (increasing as a target is approached) suggests pathology where?
cerebellum
Describe chorea.
involuntary abrupt, irregular movements that flow as if randomly from one body part to another - smooth, dance-like
Chorea is usually accompanied by an inability to maintain a sustained muscle contraction. How can you test for this on exam?
have them stick their tongue out and they won’t be able to keep it protruded (serpentine tongue)
also won’t be able to maintain a tight handgrip (milkmaid grip)
Besides Hungington disease, what are some other causes of chorea?
Post-streptococcal (Sydenham chorea) pregnancy hyperthyroidism alcohol wilson disease SLE
What is the word for unilateral large-amplitude and poorly patterned flinging or flailing movements of a limb?
hemiballismus
What is the usual cause of hemiballismus?
contralateral lesion in the caudate, putamen or subthalamic nucleus (stroke is the most common)
hyperglycemia can also cause it though
What is the tyipcal management for hemiballismus?
dopamine-depleting agents like reserpine or tetrabenazine
if severe, consider contralateral thalamotomy or pallidotomy
One of the features of dystonia is “gest antagoniste”. What does that mean?
it means they may be diminished by sensory tricks like gently touching the affected body part
If the dystonia is occurring at rest, does this mean it’s probably a primary or secondary dystonia?
probably secondary - like from drugs
in primary dystonia, the dystonia typically presents first as an action dystonia. If it has progressed to dystonia at rest, that suggests it’s quite severe
One example of a primary dystonia is idiopathic torsional dystonia. What is the inheritance pattern and what is the mutation?
autosomal dominant
on chromosome 9q, an ATP-binding protein called Torsin A
What is the treatment of choice for familial dystonia?
botulinum toxin for the affected muscles
What are some examples of how idiopathic torsion dystonia may present?
torticollis
writer’s cramp
blepharospasm
spasmodic dysphonia
What is the difference between positive myoclonus and negtative myoclonus?
positive myoclonus is a sudden lightning-like movement produce by abrupt and brief muscle contraction
negative myoclonus is the opposite, where the movement occurs due to inhibition of a specific muscle
What are some causes of myoclonus?
physiologic hypnic jerks, hiccups, myoclonic epilepsies, metabolic encephalopathy, wilson disease, CJD, hypoxic brain injury
What is the most effective treatment for myoclonus?
clonazepam
What are tics?
abrupt, stereotyped, coordinated movements or vocalizations (can be simple or complex), often exacerbated by stress and relieved by distraction
What is the most effective therapy for tics?
dopamine antagonists like haloperidol or the atypical antipsychotics
What is the typical clinical presentation for Wilson’s disease?
liver dysfunction and neuropsychiatric symptoms
What is the general pathologic issue in Wilson’s disease?
mutation of a copper-binding protein leading to impaired conjugation of copper to ceruloplasmin and entry of copper into the biliary excretory pathway
this results in copper buildup in the liver and spillover into the systemic circulation with deposition in the kidney, cornea (Kayser-Fleischer rings in Descemet’s membrane) and CNS
What is the most sensitive screening test for Wilson’s disease?
24-hour urinary copper excretion
serum copper levels may be increased and serum ceruloplasmin levels may be decreased, but not always
What is the treatment for Wilson’s disease?
copper chelation with D-penicillamine or trientine in conjugation with zinc
The paroxysmal dyskinesias are a rare group of movement disorders characterized by what?
recurrent attacks of hyperkinesis with preserved consiousness
can be triggered by sudden movements, alcohol, fatigue, stress, exercise, etc.
What is the best treatment for paroxysmal dyskinesias?
carbamazepine
