movement disorders

Question 1

main output structures of the basal nuclei

Answer 1

endopedoncular nucleus, substancia nigria

Question 2

direct pathway of movement control

Answer 2

dopaminergic innervation of caudate/putamen from the substancia nigria increase inhibition of the subsantcia nigria/EPN by activating D1 recept on gabapergic medium spiny neuron. this release the thalamus from tonic inhibition. This increase the excitatory feedback from the thalamus to motor cortex and caudate/putamen.
PROMOTE MOVEMENT

Question 3

dopaminergic receptor in motor control

Answer 3

• D1 recept: increase glutamatergic activity, direct pathway
• D2 recept: decrease glutaminergic activity

Question 4

indirect pathway of movement control

Answer 4

medium spiny neurons inhibit GABAergic neuron in globus palidus. This release the subthalamic nucleus from inhibition, increasing excitation of SN/EPN, and in turn inhibition of thalamus. Decrease thalamic excitation of motor cortex and caudate/putamen
INHIBITS MOVEMENT

Question 5

dopamine promote or inhibit movement ?

Answer 5

promote: excite medium spicy neuron through D1 recep in direct pathway, inhibit through D2 in indirect

Question 6

role of cerebellum in pathophysiology of hyperkinetic disorder

Answer 6

lateral cerebellar nucleus conected to striatum via intralaminar nucleus of thalamus

Question 7

clinical signs resulting from peripheral nerve hyperexcitability

Answer 7

fasciculation, myokymia, neuromyotomia, cramps, tentany, tetanus

Question 8

define myokymia (EMG, channel)

Answer 8

continuous contraction of facial/limb myofibers, often exhibiting an **vermicular **movement of the skin overlying the affected muscle.
EMG: burst of single motor unit potential firing at 5-150 Hz
believed to result from abnormal K channel function.
Persist during sleep

Question 9

define tremors

Answer 9

involontary rythmic oscillatory movement of a body part with **symmetric velocity **in both direction of movement.
frequency 1-12 Hz

Question 10

classification of tremors

Answer 10

1. rest tremors (not in animal)
2. action tremors: postural (orthostatic, idiopathic head tremors, begnin/idiopathic/rapid postural tremors) and kinetic (intention tremors)

Question 11

define neuromyotomia (EMG)

Answer 11

generalized muscle stiffness with delayed relaxation, often resulting in collapse. Muscle rippling. May be precipited by stress/ excitement
EMG: high frequency (150-300 Hz) burst of decrementing discharge of motor unit potentials with abrubt onset/offset. Spontaneous or initiated by needle movement, volontary contraction percussion of the nerve
Persist during sleep, can be blocked by neuromuscular bloking agent

Question 12

define cramp

Answer 12

sudden, severe, and involuntary muscle contraction or over‐shortening that is generally temporary and benign. Can cause mild‐to‐excruciating pain, and immobility of the affected muscle(s). Onset is usually sudden, and resolves on its own over a period of several seconds, minutes, or hours.
reported with hypoadrenocorticism
EMg: repetitive firing of motor unit action potential at high rate (up to 150 Hz). Number of MU activated and frequency of discharge increase gradually and subside gradually with irregular firing pattern.
Electrically silent cramp with strenous/ischemic exercice in metabolic myopathy associated with defect glycolysis/glycogenolysis

Question 13

define tetany

Answer 13

Sustained muscle contraction, usually involving extensors muscles. No relaxation is noted. May be accompanied by sensory changes (eg, hypocalcemia‐induced tetany).

Question 14

define tetanus

Answer 14

Severe, sustained muscle contraction resulting from impairment of glycine release within the **ventral gray matter **of the spinal cord resulting from exotoxin release associated with Clostridium tetani infections.

Question 15

epileptic and non epileptic myoclonus

Answer 15

Epileptic:
1. Lafora
2. neuronal ceroid lipofuscinosis
3. feline audiogenic reflex seizure
4. juveniel myoclonic epilepsy in Rhodesian Ridgebacks

Non epileptic:
1. Canine distemper virus
2. Startle disease
3. Hemifacial spasm

Question 16

define myoclonus

Answer 16

A sequence of repeated, variably rhythmic, brief shock‐like jerks resulting from the sudden involuntary contraction or relaxation of 1 or more muscles. Generates movement of the affected body part. Differs from a startle response in that myoclonic movements frequently occur independent of a sudden stimulatory input and occur repetitively. May be precipitated or worsened by movement, stress. May occur during sleep.

Question 17

causes of generalised peripheral nerve hyperexcitability

Answer 17

hereditary, immune-mediated, paraneoplasic, polyneuropathies, motor neuron diseases, neurodegenerative, metabolic, begnin (stress/exercise), toxicity

Question 18

define athetosis

Answer 18

Prolonged slow involuntary contraction of the distal part > trunk muscles resulting in nonrhythmic bending/sinuous/writhing movements. May occur at rest or may be worsened or precipitated by movement.

Question 19

define ballism

Answer 19

An **abrupt **involuntary contraction of proximal limb muscles resulting in **large‐amplitude flailing/flinging movements **of the limb(s); typically unilateral.

Question 20

define chorea

Answer 20

An abrupt, irregular, and unsustained low‐amplitude contraction of muscle groups, particularly **distal **muscles resulting in 1 or more discrete movements. Similar in distribution to athetosis but faster and larger amplitude. Not characterized by an inserted posture (as in dystonia) but rather an inserted movement.

Question 21

define dystonia

Answer 21

A sustained, slow, involuntary contraction of agonist and antagonist muscles of a body region producing abnormal postures and/or involuntary movement of portions of the body along a longitudinal axis. May appear as a twisted posture of the limbs, trunk, or neck. Associated with varying durations of muscle contracture (arrhythmic). Only occurs in wakeful state.

Question 22

define fasciculation

Answer 22

A **brief **spontaneous contraction resulting from the spontaneous activation of a small number of muscle fibers, often causing a vermicular movement under the skin.

Question 23

define myoclonic tremor

Answer 23

Likely replaced by term rhythmic myoclonus: brief shock‐like myoclonic movements occurring with a **defined unidirectional fast phase **(positive or negative) and a slower recovery phase.

Question 24

define myotomia

Answer 24

A disturbance in muscle relaxation after voluntary contraction or percussion. Is most noticeable after a period of rest, and improves with continued activity. Frequently results in noticeable **hypertrophy **of the affected muscles and may lead to diminished joint flexion when walking

Question 25

etiological classification of canine paroxysmal dyskinesia

Answer 25

**inherited or presumed inherited: **
* episodic hypertonicity in CKCS
* paroxysmal dyskinesia in Border Terrier
* Scotty cramp
* PD in the soft coated wheaton terrier
* PD inChinooks
* Dancing Dobermann disease
* Paroxysmal kinesigenic dyskinesia in German Shorthaired Pointer
* PD in Labrador and Jack Russel Terrier

Acquired:
* drug administration (propofol, phenobarbital) and structural intracranial lesion
* paroxysmal gluten-sensitive dyskinesia in Border Terrier

Question 25

mutation PD in Kerry Blue terrier / chinese crested

Answer 25

SERAC1 (canine multiple sytem degeneration)

Question 26

mutation PD in CKC

Answer 26

BCAN

Question 27

mutation PD in Soft-coated wheaten terrier

Answer 27

PIGN

Question 28

mutation PD in Shetland Sheepdog

Answer 28

PCK2

Question 29

mutation/breed for myotonia congenita

Answer 29

miniature Schnauzer, Australian Cattle, Jack Russel Terrier

Question 30

mutation/breed for inherited myokymia

Answer 30

KCNJ10
Jack Russel, Parson Russel, Russel terrier, Toy fox terrier, smooth fox terrier, Belgian Malinois, Chihuahua

Question 31

mutation/breed for myoclonic epilepsy (Lafora)

Answer 31

EPM2
miniature wire-haired Dashund, beagle

Question 32

muatation/ breed for startle disease (hyperekplexia)

Answer 32

SLC6A5
Irish Wolfhound

Question 33

Definition neuromyotonia

Answer 33

more severe form of myokymia, seen as persistent muscle stiffness and delayed muscle relaxation due to abnormal electrical discharges of motor nerves.

Question 34

Describe the effect of dopamine on basal nuclei.

Answer 34

Direct pathway activation
Substancia nigra, pars compacta -> dopamine -> D1R of medium spiny neurons in CN & putamen -> increase GABA inhibition on substancia nigra, pars reticularis -> decreased inhibition of thalamus -> activation of motor cortex -> promotes movements

Indirect pathway inactivation
Substancia nigra, pars compacta -> dopamine -> D2R of medium spiny neurons in CN & putamen -> decrease GABA inhibition of globus pallidus -> increase GABA inhibition of subthalamic nucleus -> decrease activation of substancia nigra, pars reticularis -> decreased inhibition of thalamus -> activation of motor cortex -> promotes movements

Question 35

What are the 3 breeds predisposed for narcolepsy? What is the gene and protein?

Answer 35

Doberman Pinscher, Labrador retriever, Dachshund

HCRTR2 (chromosome 12)
Hypocretin receptor 2