movement disorders Flashcards
JVIM 2021
main output structures of the basal nuclei
endopedoncular nucleus, substancia nigria
direct pathway of movement control
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
dopaminergic receptor in motor control
- D1 recept: increase glutamatergic activity, direct pathway
- D2 recept: decrease glutaminergic activity
indirect pathway of movement control
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
dopamine promote or inhibit movement ?
promote: excite medium spicy neuron through D1 recep in direct pathway, inhibit through D2 in indirect
role of cerebellum in pathophysiology of hyperkinetic disorder
lateral cerebellar nucleus conected to striatum via intralaminar nucleus of thalamus
clinical signs resulting from peripheral nerve hyperexcitability
fasciculation, myokymia, neuromyotomia, cramps, tentany, tetanus
define myokymia (EMG, channel, persistance with sleep)
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
define tremors
involontary rythmic oscillatory movement of a body part with symmetric velocity in both direction of movement.
frequency 1-12 Hz
classification of tremors
- rest tremors (not in animal)
- action tremors: postural (orthostatic, idiopathic head tremors, begnin/idiopathic/rapid postural tremors) and kinetic (intention tremors)
define neuromyotomia (EMG)
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
define cramp
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
define tetany
Sustained muscle contraction, usually involving extensors muscles. No relaxation is noted. May be accompanied by sensory changes (eg, hypocalcemia‐induced tetany).
define tetanus
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.
epileptic and non epileptic myoclonus
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
define myoclonus
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.
causes of generalised peripheral nerve hyperexcitability
hereditary, immune-mediated, paraneoplasic, polyneuropathies, motor neuron diseases, neurodegenerative, metabolic, begnin (stress/exercise), toxicity
define athetosis
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.
define ballism
An abrupt involuntary contraction of proximal limb muscles resulting in large‐amplitude flailing/flinging movements of the limb(s); typically unilateral.
define chorea
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.
define dystonia
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.
define fasciculation
A brief spontaneous contraction resulting from the spontaneous activation of a small number of muscle fibers, often causing a vermicular movement under the skin.
define myoclonic tremor
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.
define myotomia
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
etiological classification of canine paroxysmal dyskinesia
inherited or presumed inherited:
* episodic hypertonicity in CKCS
* paroxysmal dyskinesia in Border Terrier
* Scotty cramp
* PD in the soft coated wheaton terrier
* PD in Chinooks
* 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
mutation PD in Kerry Blue terrier / chinese crested
SERAC1 (canine multiple sytem degeneration)
mutation PD in CKC:
molecule
syndrome name
coat color
prognosis
treatment
BCAN (brevican, brain prot of extracellular matrix of proteoglycan)
episodic falling syndrome, not induced by exercise
maj Ruby, Black tan
improves with age
treat: clonazepam, acetalozamide
mutation PD in Soft-coated wheaten terrier
mol, treatment
PIGN
non-kinesigenic, can be induced by excitement
bisynthesis of glycosylphosphatidylinositol
flex/est hind limbs
treat: acetalozamide
mutation PD in Shetland Sheepdog
treatment
mol
transmission
PCK2
triggered by exercice, ataxia, hypermetria, hypertonia, tremors
gluten free diet
PCK2 : mitochondrial phosphoenolpyruvate carboxykinase 2
hypothet autosom domint
mutation/breed for myotonia congenita
miniature Schnauzer, Australian Cattle, Jack Russel Terrier
Mutations in a skeletal muscle voltage-dependent chloride channel, CIC-1
mutation/breed for inherited myokymia
KCNJ10
Jack Russel, Parson Russel, Russel terrier, Toy fox terrier, smooth fox terrier, Belgian Malinois, Chihuahua
mutation/breed for myoclonic epilepsy (Lafora)
EPM2B (NHLRC1)
miniature wire-haired Dashund, beagle
muatation/ breed for startle disease (hyperekplexia)
SLC6A5
Irish Wolfhound
Definition neuromyotonia
more severe form of myokymia, seen as persistent muscle stiffness and delayed muscle relaxation due to abnormal electrical discharges of motor nerves.
Describe the effect of dopamine on basal nuclei.
1/ 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
2/ 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
What are the 3 breeds predisposed for narcolepsy? What is the gene and protein?
Doberman Pinscher, Labrador retriever, Dachshund
HCRTR2 (chromosome 12)
Hypocretin receptor 2
Breeds overrepresented for idiopathic head tremor syndrome? Structural?
Idiopathic episodic head tremors
English Bulldog
Boxer
Lurcher
CKCS
Doberman Pinscher
Labrador Retriever
Structural episodic head tremors
French Bulldogs
Labrador retriever
What is the classification of tremors?
1/ Resting tremors: not reported in vet medicine
2/ Action tremors
Postural or orthostatic tremors: when standing and dissipates on activity or upon lying down
- Orthostatic tremors: giant breeds, <2 yo, standing, may involve head and trunk, high EMG frequencies (13-18 Hz) ->PATHOGNOMONIC
- Idiopathic head tremors
- Benign, idiopathic, rapid postural tremors: old dogs, benign, stretch reflex disturbance?
Kinetic tremors: during any aspect of the voluntary movement
Intention tremors
Cerebellitis
What are the different findings in twitches (or peripheral nerve hyperexcitability) compared to tremors and myoclonus?
Sustained twitching or muscle contractions of variable frequency and amplitude -> different to tremors that have uniform frequency
Do not result in significant movement in the affected body segment -> different to myoclonus
Myokymia and neuromyotonia persist during sleep and anaesthesia
Name the structures implied in narcolepsy and corresponding neutrotransmitter.
Suprachiasmatic nucleus (ventrolateral hypothalamus) – hypocretin
Locus coeruleus – norepinephrine
Dorsal raphe – serotonin
Pontine reticular formation center – acetylcholine
Which breed is predisposed to orofacial pain syndrome?
Burmese
Give 3 clinical signs of narcolepsy
Daytime sleepiness
Cataplexy
Shorter sleep latency
(& hypnagogic hallucinations)
Which tests are altered by gabapentin in cats?
Alteration of gait analyses and postural reactions
No impairment of cranial nerves examination and spinal reflexes
Tremors cease during sleep: true or false?
True
Tremors are only awake
What are the two clinical criteria in favour of secondary episodic head tremors?
Additional neurological signs
Older age
What are structures are involved in secondary episodic head tremors?
Mesencephalic aqueduct
Third ventricle
Interthalamic adhesion
Some combination of these
What is the most common underlying condition in dogs with secondary episodic head tremors?
Pituitary mass
Which breed is overrepresented in dystonic head tremors?
Poodle / poodle-cross (40%)
Provocative tests, prevention tests, and therapy of narcolepsy
Provocative tests:
Physostigmine (carbamate, cholinesterase inhibitor)
Food
Prevention tests:
Imipramine (norepinephrine reuptake inhibitor + anticholinergic)
Atropine (anticholinergic)
Therapy:
Imipramine (norepinephrine reuptake inhibitor + anticholinergic)
Methylphenidate (amine, sympathomimetic)
Selegiline (monoamine oxidase inhibitor)
Yohimbine (alpha 2 antagonist)
A _____ tremor occurs when standing, but dissipates on activity or when lying down.
Orthostatic/Postural
Which hormone is mainly implicated in canine narcolepsy ?
Hypocretin
What are the 2 auto-antibodies associated with PxD in Border Terrier?
Anti-gliadin: AGA-IgG
Anti-transglutaminase 2: TG2-IgA
What is the difference between peripheral myoclonus and spinal segmental myoclonus?
Peripheral myoclonus (PM): focal jerks affecting muscles in the distribution of a peripheral nerve root or nerve at the level of the nerve root involved.
Spinal segmental myoclonus (SSM): rhythmic movements in the area innervated by the affected spinal segment -> related to spinal cord pathology (due to spinal cord injury, herpes myelitis, or demyelinating disease in human beings).
What are the differentials for exercise-induced fatigue in dogs ?
Neurologically normal:
Myasthenia
Hypoglycaemia
Hyper or hypokalemia
Muscular dystrophy
EIC (Labradors)
Exertional rhabdomyolysis
Metabolic myopathies (pyruvate, lactate)
Mitochondrial myopathies
Neurologically abnormal:
Myasthenia
Polymyopathy
Muscular dystrophy
Polymyositis
Hypoglycaemia
Hyper or hypokalemia
Which CNS anatomical structure is believed to cause positional head tilt? Which PNS disease can cause similar clinical presentation in cats?
Cerebellar nodulus and uvula
Hypokalaemic myopathy
What is the most common cause of tetany in dogs?
Tetany occurs most commonly in dogs with hypocalcemia associated with parturition (puerperal tetany) or hypoparathyroidism
Which reflex can be abolished in exercice induced collapse dogs during an episode?
Patellar
Withdrawal reflex is intact during episode.
Patellar is normal at rest.
causes of positional head tilt
head tilt to oposite side when animal turn his head. lesion of NU or muscle spindles of oblicus/rectus capitis m
dog: cerebellar nodulus/uvula hypopasia in lysosomal storage disease
gliomatosis cerebri affecting nodulus/uvula
cat: hypokaliemy
myasthenia gravis
% REM sleep disorder in dog with tetanus
53%, not associated with prognosis
days/months after tetanus
orthostatic tremors (freq)
high freq tremors (13-21Hz) during standing position
young giant or large breed, maj PL
Retriever later in life
reluctant to lie down
treat gabapentine, pheno (partial improv)
slowly progressive
begnin idiopath postural tremors
old dog, not associated with diff lying down, do not disappear with weight bearing test
startle disease
Spanish greyhounds, Irish wolfhound
presynaptic glycine transporter SLC6A5
hypertonia and apnea that is triggered by noise and/or touch
onset 2m
mut + breeds associated with myotonia congenita
unusula sign in FB, Lab
CLCN1 (chloride channel)
Labrador, American Bulldog, Miniature Schnauzer, JRT, French Bulldog
cat, goat
high frequency discharge with waxe/wane amp/freq
muscle stiffness after initiation of movement (or startle) and a bunny-hop type movement when running, with gait improvement after warm-up
dysphagia in Labrador, french Buldog (maj sign
mutations associated with m hypertrophy (maj shoulder and neck) dysphagia and gait abnomal in French Buldog
CLCN1 and PDE4C
differential: dystrophin dystrophy (increase CK)
unusual manif of myotonia congenita in cat
blepharospasm, dysphonia, facial spasm, dysphagia, protrusion IIIrd eyelid, resistance opening mouth
breed with paradoxial pseudomyotonia + mut in cattle + treat
English springer
Cocker spaniel
exercice induced generalised myotonic-like event
in cattle ATP2A1
treat clonazepam
def paroxysmal dyskinesia
involontary hyperkinetic self limiting mvt disorder
local: basal nuclei or cerebellum
types of parox dyskinesia
- kinesigenic (after mvt)
Markieje - non-kinesigenic (can occur at rest)
others - exertion-induced (fatigue)
PD in Het Markiesje
mut SOD1
at 10-12 weeks severe tetraparesis, cramping
PD in Weimaraner
mut, prot, signs
mut TNR tenascin (extracell matrix glycoprot)
ataxia, collapse, kyphosis, low head carriage
treatments for paroxysmal dyskinesia
- Fluoxetine : Scottish, Weimaraner
- Gluten-free diet: Maltese, Border Terrier, Shetland Sheepdog (fresh meat)
- Clonazepam: Labrador PD, CKCS BCAN
- Levetiracetam: Welsh Terrier
- Acetalozamide: Labrador PD, CKCS BCAN, soft coaten Wheaten terrier
molecules causing dyskinesia
phenobarbital
proprofol
metoclopramide
metronidazole
most common affected breed with dystonic head tremors
Poodle
accompagned by abnormal posture, does not occur during complete rest
most common condition associated with nonintentional head tremor
pituitary mass
often comp mesencephalic aq, third vent or interthal adhesion
spinocerebellar ataxia without neuromyotonia
Bouvier des Ardennes (KCNJ10)
Parson Russel Terrier (CAPN1)
self limiting paroxysmal dyskinesia
Labrador retriever
Jack Russel Terriers
30% spont remission, 75% improvement
cat breed with dyskinesia
sphynx
acetalozamide
localisation associated with bruxism
forebrain (diencephalic)
neoplasia, MUO
