Clinical Movement disorders I - Hyperkinetic disorders Flashcards
Diagnosis of a movement disorder
Type of movement (phenomenology):
(1) Usually not purely a deficit
(2) Ballismus, chorea/athetosis, dystonia, bradykinesia, tremor, tic, myoclonus, ataxia
(3) Divided into hyperkinetic and hypokinetic categories
Association with other neurologic signs or symptoms
Investigation of possible etiologies
(1) Genetic, structural, toxic, idiopathic, etc.
Types of abnormal movements
list
Types of movements: ballismus, chorea/athetosis, dystonia, bradykinesia/hypokinesia, tremor, tics, myoclonus, ataxia
Ballismus or ballism
def
(1) Sudden flinging movements of an entire limb
(2) Usually due to a lesion in the subthalamic nucleus (3) Usually unilateral
Chorea/athetosis
def
Nearly continuous movements which may affect one or more limbs and possibly the trunk
Chorea (which means “dance”) typically causes brisk, distal movements
Athetosis (which means “not fixed” or “not steady”) typically causes proximal, writhing movements
Chorea/athetosis is a spectrum, and patients often have both types of movement
Chorea/athetosis disorders
HD
chars
(i) Autosomal dominant
(ii) Expanded trinucleotide repeat (CAG) > 30
(iii) Chromosome 4
(iv) Caudate nucleus atrophy
Dysimmune chorea
causes
Sydenham’s chorea: post-infectious
Chorea gravidarum
SLE
Toxic chorea
causes
CO poisoning
Over-medicated parkinson’s
Dystonia
def
Dystonia is a continuous or nearly continuous involuntary contraction of a group of muscles causing an abnormal posture. It may be
a. Focal, affecting a limb or part of a limb
b. Segmental, affecting multiple muscles innervated by the same segments of the spinal cord
c. Generalized
Dystonias
MOI/gene
Early-onset generalized torsion dystonia
MOI: AD
Gene: Torsin A
Dystonias
MOI/gene
DOPA-responsive dystonia
MOI: AD
Gene: GTP- cyclohydrolase
Dystonias
MOI/gene
Sagawa Syndrome
MOI: AR
Gene: Tyrosine Hydroxylase
Dystonias
MOI/gene
Paroxysmal nonkinesigenic dyskinesia
MOI: AR
Gene: Myofibrillogenesis Regulator-1 (MR1)
Causes of dystonia
Gen list
Genetic
Idiopathic
Toxic
Structural injury involving basal ganglia
Causes of dystonia
Genetic
chars
(i) Generalized, usually pediatric onset
(ii) Genetic focal dystonias, including some cervical dystonia
Causes of dystonia
Idiopathic
chars
(i) Cervical dystonia (torticollis, wry-neck) is most common
(ii) Other focal dystonias can occur idiopathically: limb dystonia, blepharospasm (dystonic eye closure), spasmodic dysphonia
(iii) Task-specific dystonia, such as Organic Writer’s Cramp
Causes of dystonia
Toxic dystonia
chars
(i) Acute dystonic reaction to neuroleptics
(ii) Tardive dyskinesia
(iii) Tetanus fits the definition of dystonia, but has a different mechanism via clostridial toxin
Causes of dystonia
Structural injury
chars
Usually involving basal ganglia
(i) Trauma
(ii) Stroke
(iii) Tumor
How to characterize a tremor
Rhythm
(i) must be regular
(ii) frequency: fast or slow
Morphology
(i) flexion/extension
(ii) pill rolling
Circumstance
(i) postural
(ii) resting
(iii) action
Essential tremor
chars
Postural tremor, 8-12 Hz
May be asymmetric but has bilateral onset
Incidence and severity increase with age
Often autosomal dominant
Essential tremor
tx
Alcohol consumption may transiently suppress the tremor
Drugs for essential tremor include primidone, beta-blockers, topiramate alprazolam, and gabapentin (Class A or B evidence)
Thalamic DBS can be used for severe and refractory tremor
Wilsons disease
Clinical presentation
Progressive hepatolenticular (liver and basal ganglia) degeneration
(i) Behavioural abnormalities are common
(ii) Causes proximal tremor or any other movement disorder
(iii) Cirrhosis
(iv) Kayser-Fleischer corneal ring (brown-green at the limbus of the cornea)
Wilson’s disease
Genetics
(i) The gene for Wilson’s disease is located at 13q14.3-q21.1
(ii) It is autosomal recessive, with a prevalence of ~30 per million (~1:100 are carriers)
(iii) It encodes ATP7B, a copper transporting P-type ATPase expressed predominantly in the liver
(iv) Over 200 disease specific mutations of ATP7B have been reported
(v) ATP7B is approximately 80 kb and contains 21 exons that encode an approximately 7.5 kb transcript
Wilson’s disease
Abnormal hepatobiliary copper excretion
There are multiple forms of ceruloplasmin, between 115 and 200 kD.
Ceruloplasmin is not always reduced, nor does the reduction in ceruloplasmin correlate with disease severity
All patients aged 6-40 years with a new movement disorder should be screened with which tests for wilson’s disease
(i) Serum ceruloplasmin (low in 73%)
(ii) 24-hr urinary copper (high in 88%)
(iii) Slit-lamp exam for Kayser-Fleischer corneal ring (present in 55%, but present in 90% if there is neurologic disease)
Tic Movements
Gen chars
a. Stereotypic
b. Repetitive
c. Irregular
d. Usually can be volitionally suppressed temporarily
e. Can be more complex than myoclonus
f. May include vocalizations
Simple motor tic
def
Simple motor tic= A single sterotypic movement
Gilles de la Tourette syndrome
chars
An inherited disorder with multiple vocal and motor tics beginning before age 21
Genetically linked to obsessive-compulsive disorder (OCD)
Often co-occurs with attention deficit hyperactivity disorder (ADHD) or antisocial conduct disorder
Common motor tics: blinking, facial twitching, shoulder shrugging
Vocal tics: grunting, barking, humming, repetitve phrases. Coprolalia (involuntary cursing) occurs in 6% of Touretters
Myoclonus
Movements are…
Movements are:
Sudden, abrupt
Focal, localized
Usually recurrent but not regular
May be generalized or segmental
Myoclonus
Originates from/frequently seen in…
May originate from cortex, brainstem reticular formation or spinal segment
Frequently seen in toxic or metabolic encephalopathy
Asterixis
Gen chars
Intermittent lapses in postural tone
Not truly rhythmic
Usually occurs in toxic-metabolic encephalopathies
Ataxia
Manifested by…
Ataxia is manifested by dysmetria and movement decomposition
a. Dyscoordination
b. Dysmetria- disturbance of placement, under- and over-shoot
c. Dysdiadochokinesis- decomposition of repetitive movements
Ataxia
Deficit of…/may be due to…
Sometimes described as a “tremor” but is not rhythmic (although cerebellar disease can cause both ataxia and tremor together)
Ataxia is a deficit of motor function
May be due to sensory or cerebellar lesion
Fibrillations & fasciculations
chars
Involve fascicles and motor units, not whole muscles
Movement disorders involve whole muscles, muscle groups or are generalized.
Hyperkinetic disorders
Lab studies that can be done for various disorders
1) MRI
(2) Wilson’s: ceruloplasmin, 24 hr urinary copper, Kayser-Fleischer rings
(3) Collagen-vascular disease: ESR, ANA, RF
(4) Post-infectious chorea: ASO
(5) Storage diseases: amino acids, RBC morphology, uric acid
(6) Genetic tests for Huntington’s & spinocerebellar ataxias (SCAs)
