Movement Disorders

Question 1

Most cases of idiopathic Parkinson Disease are sporadic, but what are some genes that have been associated with familial forms?

Answer 1

SNCA (alpha-synuclein)
PARK2 (E3 ubiquitin ligase)
UCHL1 (ubiquitin carbosyterminal esterase L1)
PINK1 (PTEN-induced putative kinase 1)
LRRK2 (leucine-rich repeat kinase 2)

Question 2

Where is the typical location for dopaminergic neuronal loss in PD?

Answer 2

the substantia nigra pars compacta

(but also the dorsal motor nucleus of the vagus nerve, anterior olfactory structures, locus coeruleus, and temporal mesocortex)

Question 3

What are the four cardinal features of PD?

Answer 3

tremor
rigidity
bradykinesia
postural instability

Question 4

Describe the tremor seen in PD?

Answer 4

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

Question 5

What percentage of patients with PD will develop dementia as the disease progresses?

Answer 5

25-30%

Question 6

Why do we give L-dopa and not just dopamine?

Answer 6

dopamine can’t cross the BBB

Question 7

WHy do we give it with carbidopa?

Answer 7

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

Question 8

What has been the proposed strategy for early therapy that will reduce the subsequent risk of dopa-induced dyskinesias?

Answer 8

using dopaminergic agonists like ropinirole

Question 9

What medication can be helpful for early treatment of the bradykinesia, rigidity and gait disturbance?

Answer 9

amantadine

Question 10

What are the characteristics of Neuroleptic Malignant Syndrome?

Answer 10

muscle rigidity, fever, autonomic lability, altered LOC, elevated CK, and leukcytosis

Question 11

What is the treatment for NMS?

Answer 11

discontinue the offending drug
antipyretics
rehydration
bromocriptine or dantrolene

Question 12

The propensity of a drug to causing tardive dyskinesia is related to its blocking activity at what receptor?

Answer 12

D2

Question 13

Describe the typical presentation of stiff man syndrome.

Answer 13

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

Question 14

What antibodies may be present in stiff man syndrome?

Answer 14

glutamic acid decarboxylase (GAD) antibodies

amphiphysin antibodies

Question 15

What is the treatment for stiff man syndrome?

Answer 15

benzodiazepines and baclofen

Question 16

What kind of tremor is seen in essential tremor?

Answer 16

postural tremor only - almost always affecting the hands, but may also affect the head, face, voice, trunk or legs; almost always bilateral

Question 17

Action or intention (increasing as a target is approached) suggests pathology where?

Answer 17

cerebellum

Question 18

Describe chorea.

Answer 18

involuntary abrupt, irregular movements that flow as if randomly from one body part to another - smooth, dance-like

Question 19

Chorea is usually accompanied by an inability to maintain a sustained muscle contraction. How can you test for this on exam?

Answer 19

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)

Question 20

Besides Hungington disease, what are some other causes of chorea?

Answer 20

Post-streptococcal (Sydenham chorea)
pregnancy
hyperthyroidism
alcohol
wilson disease
SLE

Question 21

What is the word for unilateral large-amplitude and poorly patterned flinging or flailing movements of a limb?

Answer 21

hemiballismus

Question 22

What is the usual cause of hemiballismus?

Answer 22

contralateral lesion in the caudate, putamen or subthalamic nucleus (stroke is the most common)

hyperglycemia can also cause it though

Question 23

What is the tyipcal management for hemiballismus?

Answer 23

dopamine-depleting agents like reserpine or tetrabenazine

if severe, consider contralateral thalamotomy or pallidotomy

Question 24

One of the features of dystonia is “gest antagoniste”. What does that mean?

Answer 24

it means they may be diminished by sensory tricks like gently touching the affected body part

Question 25

If the dystonia is occurring at rest, does this mean it’s probably a primary or secondary dystonia?

Answer 25

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

Question 26

One example of a primary dystonia is idiopathic torsional dystonia. What is the inheritance pattern and what is the mutation?

Answer 26

autosomal dominant

on chromosome 9q, an ATP-binding protein called Torsin A

Question 27

What is the treatment of choice for familial dystonia?

Answer 27

botulinum toxin for the affected muscles

Question 28

What are some examples of how idiopathic torsion dystonia may present?

Answer 28

torticollis
writer’s cramp
blepharospasm
spasmodic dysphonia

Question 29

What is the difference between positive myoclonus and negtative myoclonus?

Answer 29

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

Question 30

What are some causes of myoclonus?

Answer 30

physiologic hypnic jerks, hiccups, myoclonic epilepsies, metabolic encephalopathy, wilson disease, CJD, hypoxic brain injury

Question 31

What is the most effective treatment for myoclonus?

Answer 31

clonazepam

Question 32

What are tics?

Answer 32

abrupt, stereotyped, coordinated movements or vocalizations (can be simple or complex), often exacerbated by stress and relieved by distraction

Question 33

What is the most effective therapy for tics?

Answer 33

dopamine antagonists like haloperidol or the atypical antipsychotics

Question 34

What is the typical clinical presentation for Wilson’s disease?

Answer 34

liver dysfunction and neuropsychiatric symptoms

Question 35

What is the general pathologic issue in Wilson’s disease?

Answer 35

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

Question 36

What is the most sensitive screening test for Wilson’s disease?

Answer 36

24-hour urinary copper excretion

serum copper levels may be increased and serum ceruloplasmin levels may be decreased, but not always

Question 37

What is the treatment for Wilson’s disease?

Answer 37

copper chelation with D-penicillamine or trientine in conjugation with zinc

Question 38

The paroxysmal dyskinesias are a rare group of movement disorders characterized by what?

Answer 38

recurrent attacks of hyperkinesis with preserved consiousness

can be triggered by sudden movements, alcohol, fatigue, stress, exercise, etc.

Question 39

What is the best treatment for paroxysmal dyskinesias?

Answer 39

carbamazepine