Movement Disorders

Question 1

Sudden, rapid, recurrent, non-rhythmic, stereotyped movements.
At least one motor and one phonic tic.
Onset before age 18 and persists >1 year.
Pathophysiology: Dopaminergic hyperstimulation of the Ventral Striatum & Limbic System.
Presentation: Coprolalia - Involuntary obscene speech.

Answer 1

Tourette’s Syndrome

Question 2

Treatment of Tourette’s Syndrome?

Answer 2

Antidopaminergic Agents: Haloperidol, Pimozide
Atypical Antipsychotics: Fluphenazine
Clonidine, Guanfacine, Tetrabenazine

Question 3

Copper-transporting P-type ATPasae (ATP7B) on chromosome 13.
Tremor: High amplitude proximal wing-beating
Characteristic grin with drooling

Answer 3

Wilson’s Disease

Question 4

Double Panda Sign
Increased T2 signal in the caudate and putamen + midbrain, thalamus

Answer 4

Wilson’s Disease

Question 5

Trinucleotide repeat CAG on chromosome 4
Pathophysiology: Neuronal degeneration in the striatum, substantia nigra, globus pallidus
MRI Brain: Caudate, Putamen atrophy

Answer 5

Huntington Disease

Question 6

Motor Impersistence: Inability to sustain tongue protrusion
Impaired saccades and pursuits
Insuppressible head movements during eye movements

Answer 6

Huntington’s Diseae

Question 7

Involuntary, rapid, abrupt, irregular movements that flow from one body part to another.
May result in dance-like gait

Answer 7

Chorea

Question 8

Autoimmune disorder manifesting with chorea, bilateral and asymmetric.
Result of Group A Streptococcus infection..
+Antistreptolysin Antibodies
+Antibasal Ganglia Antibodies

Answer 8

Syndenham’s Chorea

Question 9

Neuroacanthocytosis

Answer 9

Mixed movement disorder (dystonia + chorea).
Labs: Acanthocytes (spiculated RBCs) on wet mount blood smear.

Hallmark: Self-mutilating behavior (Compulsive head banging, biting tongue). Smacking movements of the mouth. Feeding Dystonia (food propelled out of the mouth by the tongue).

Classifications:
1. Core Syndromes: McLeod Syndrome, Pantothenate-Kinase-Associated Degeneration (PKAN)
2. with Lipoprotein Disorders: Hemolysis, Myopathy, Cardiomyopathy, Areflexia, Chorea, elevated Cr Phosphokinase, Liver disease

Question 10

Subtypes of Neuroacanthytosis

Answer 10

Chorea-Acanthocytosis
Mcleod’s Syndrome
Abetalipoproteinemia
Brain Iron Accumulation Syndromes

Question 11

Autosomal Recessive Disorder resulting from mutations in the VPS13A Gene that encodes Chorein Protein.
Presentation: Orolingual dystonias (Tongue Protrusion Dystonia), Self-mutilating behavior

Answer 11

Chorea-Acanthocytosis

Question 12

Neurodegenerative Autosomal Dominant resulting from expansion of trinucleotide repeat CAG on chromosome 12.
Common in people of Asia descend.
Clinical Features: Myoclonus, Choreoathetosis, Epilepsy, Dystonia, Tremor, Parkinsonism, Cognitive dysfunction

Answer 12

Dentatorubral-Pallidoluysian Atrophy

Question 13

Hyperkinetic movement disorder characterized by forceful, flinging, high-amplitude choreiform movements

Answer 13

Ballism

Question 14

Hemiballism can occur as a result of injury to…

Answer 14

Contralateral Subthalamic Nucleus

Question 15

Treatment for Tardive Dyskinesias

Answer 15

Clonazepam, Tetrabenazine

Question 16

Common in people with Japanese ancestry
Trinucleotide CAG repeat to Chromosome 13, producing Protein Atrophin-1
Presentation: Progressive Myoclonus Epilepsy, Ataxia, Choreoathetosis, Dementia
Path: Degeneration of the Dentate Nucleus, Red Nucleus, Globus Pallidus, STN

Answer 16

Dentatorubropallidoluysian Atrophy (DRPLA)

Question 17

Subtype of Neurodegeneration with Brain Iron Accumulation (NBIA Type 1)
Due to mutation of Pantothenate Kinase Gene (PANK2) in chromosome 20.
Path: Iron deposition and high concentration of Lipofuscin & Neuromelanin in the Substantia Nigra pars Reticulata & GPi.
Presentation: Progressive personality changes, Cognitive decline, Dysarthria, Motor difficulties, Spasticity, Choreoathetosis tremor, Retinitis Pigmentosa,
MRI: Decreased T2 signal in GP & Substantia Nigra (Eye of the Tiger)

Answer 17

Pantothenate Kinase-Associated Neurodegeneration (PKAN)

Question 18

Autosomal Dominant
Mutation in the Torsin A Gene - DYT1 Dystonia
Common in Ashkenazi Jewish descent
Presentation: Onset in childhood with action-induced limb dystonia -> Generalization
T/M: Anticholinergics, BZDs, DBS in GPi

Answer 18

Primary Generalized Dystonia
Oppenheim Dystonia
Dystonia Musculorum Deformans

Question 19

Mutation in the Sarcoglycan Protein

Answer 19

Myoclonus-Dystonia Syndrome
DYT11

Question 20

X-linked
Males of Filipino descent

Answer 20

Lubag Disease
DYT3 Dystonia

Question 21

THAP-1 Mutation

Answer 21

Adult-Onset Craniocervical Dystonia with Laryngeal involvement
DYT6

Question 22

Most common hereditary form of dopa-responsive dystonia
Autosomal dominant - Mutation in GTP cyclohydrolase I (GCHI) on chromosome 14
Common in females
Diurnal variation - worse in the PM & QHS
T/M: Low dose levodopa

Answer 22

DOPA-responsive Dystonia
Segawa’s Syndrome
DTY5

Question 23

Rhythmic palatal movements that may lead to audible clicks due to Eustachian tube contractions (clicking in the ear).
Essential (without cause) vs. Symptomatic (2/2 brainstem lesion - stroke or tumor).
Persists during sleep.
Path: Dysfunction in pathways connecting the Dentate nucleus, the Inferior Olive, Red Nucleus (Guillain-Mollaret Triangle)
MRI: Hypertrophy of the Inferior Olive

Answer 23

Palatal Myoclonus / Palatal Tremor

Question 24

Patterned, repetitive, stereotyped movements or vocalizations that occur in response to an external or internal stimulus.
Ex: Head nodding, Arm flapping, Body rocking, Head banging, Grunting, Humming, Moaning.
May occur in normal children during times of excitement/boredom, More common in children with developmental delay & autism.

Answer 24

Stereotypies

Question 25

Episodes of hyperkinetic abnormal movements (dystonia, chorea, choreoathetosis, ballism, dysarthria) with intervening normalcy. Precipitated by sudden movement, startle, hyperventilation. Familial (PRRT2 gene mutations) vs. Sporadic. T/M: ASMs (Carbamazepine)

Answer 25

Paroxysmal Kinesigenic Dyskinesias (PKDs)

Question 26

Mutation in Myofibrillogenesis Regular (MR-1) gene. Attacks may last several hours without clear precipitants. Episodes aggravated by alcohol, caffeine, fatigue. T/M: Not responsive to ASMs.

Answer 26

Paroxysmal Nonkinesigenic Dyskinesia (PNKD)

Question 27

Episodes of hyperkinetic abnormal movements triggered by prolonged exercise. Mutation in Glucose-1 Transporter (GLUT-1) gene.

Answer 27

Paroxysmal Exertional Dyskinesias (PED)

Question 28

Part of the syndrome of autosomal dominant nocturnal frontal lobe epilepsy

Answer 28

Paroxysmal Hypnogenic Dyskenias

Question 29

Episodes of ataxia in association with facial twitching, myokymia, neuromyotonia. Triggered by startle, movement, exercise. Due to mutation in KCNA1 on chromosome 12 T/M: ASMs (Carbamezapine)

Answer 29

Episodic Ataxia Type I (EAI)

Question 30

Mutation in KCNA1 on chromosome 12

Answer 30

Episodic Ataxia Type I (EAI)

Question 31

Episodes of ataxia may be associated with brainstem symptoms (nystagmus, dysarthria). Triggered by stress and alcohol. Mutation in the calcium channel CACN1A4. T/M: Acetazolamide

Answer 31

Episodic Ataxia Type II (EAII)

Question 32

Mutation in the calcium channel CACN1A4.

Answer 32

Episodic Ataxia Type II (EAII)

Question 33

Autosomal Dominant Attacks ataxia with tinnitus and vertigo with attacks of myokymia in between. T/M: Acetazolamide

Answer 33

Episodic Ataxia Type III (EAIII)

Question 34

Episodes of ataxia with ocular motion abnormalities. Triggered by sudden head movements

Answer 34

Episodic Ataxia Type IV (EAIV)

Question 35

Exaggerated startle response. Ex: Blinking, Flexion of the neck and trunk, abduction & flexion fo the arms - or - prolonged tonic startle spasms. Familial forms result from mutations in the Glycine receptor and presynaptic glycine transporter

Answer 35

Hyperekplexia

Question 36

Autosomal Dominant CAG repeat = Toxic *gain of function* = Misfolded protein product and aggregation. Presents in 3rd-5th decade of life Progressive truncal + limb ataxia, spasticity, UMN findings, CN abnormalities, Neuropathy. MRI Brain: Cerebellar Atrophy

Answer 36

Spinocerebellar Ataxias (SCAs)

Question 37

Autosomal Recessive CAG repeat on gene Ataxin 3 on chromosome 14 Truncal/Limb Ataxia, Cerebellar signs, Facial/Tongue Atrophy, Fasciculations, Bulbar symptoms

Answer 37

SCA-3 Machado-Joseph Disease

Question 38

Halo Sign

Answer 38

Hyperintense lesion on T1 in the cerebral peduncles seen in *Beta-Propeller Protein-associated Neurodegeneration*

Question 39

Eye of the Tiger

Answer 39

Hyperintensity surrounded by hypointensity in the basal ganglia seen in PKAN