Transcript hyperkinetic_syndrome

HYPERKINETIC
SYNDROMES
SAMIH BADARNY
Parkinson and other movement disorders clinic
Neurology Department
Carmel Medical Center- Haifa
TREMOR
Definition:
 Oscillatory , usually rhythmical and regular
movements affecting one or more body
parts.
 Usually caused by alternating contraction of
agonist and antagonist muscles
Classification by state of activity
 Rest Tremor: is present when a limb is fully
supported against gravity and the relevant muscles
are not voluntarily activated.
 Action tremor:
occurring during any voluntary
muscle contraction which includes postural,
kinetic, isometric and task specific tremors.
Postural tremor: is apparent during the
voluntary maintenance of a particular posture
which is opposed by the force of gravity.
Kinetic tremor: is evident during any type of
movement.
Intention or terminal tremor: is the
pronounced exacerbation of kinetic tremor
towards the end of a goal directed movement.
Task specific tremor: only occurs during the
performance of a highly skilled activity
Isometric tremor: Occurs when a voluntary muscle
contraction is opposed by a rigid stationary object.
Orthostatic tremor: A 14-16Hz tremor that appears a
few seconds after standing and subside on sitting or
walking
Classification by etiology:
Physiological and enhanced physiological:
 Present at action.
 Is more pronounced during periods of fatigue fear
or excitement.
 Results from numerous factors including the heart
beat, low pass filtering properties of striated
muscles, motor neurons firing and
synchronization by spindle feed back.
Parkinsonian tremor:
 Slow 3-5 Hz rest tremor (pill rolling)
involving the limbs and/or tongue chin
and lips.
 May be asymmetrical.
 May be accompanied by postural
(“re-mergent”) tremor.
Dystonic Tremor:
 A jerky irregular action tremor intermingled
with sustained muscular spasms that can
last several seconds.
 May involve the muscles of the neck
(tremulous spasmodic torticollis), face
(orofacial dyskinesia), trunk and limbs.
Midbrain (“rubral”, “Cerebellar outflow”) tremor:
 A tremor which is present at rest, worse on
posture and is further exacerbated by movement.
 This type of tremor is most commonly seen in
MS and brainstem vascular lesions.
Cerebellar Tremor:
 A kinetic tremor with marked intentional component.
 The tremor is usually accompanied by disorders of
ocular motility ( dysmetria, nystagmus) incordination,
DDK pendular reflexes and unsteady gait.
ESSENTIAL TREMOR
Essential tremor (ET) is the most
common movement disorder. It is a
syndrome characterized by a
slowly progressive, rapid (4-12Hz),
postural and/or kinetic tremor,
usually affecting both upper
extremities.
Epidemiology
 The estimated prevalence of ET is 0.3- 5.6% of the
general population.
 Both sexes are affected equally although head
tremor may be more frequent in women.
 The prevalence of ET increases with age.
 Age of onset has bimodal peaks - one in late
adolescence to early adulthood and a second in
older adulthood. The mean age at presentation is
35-45 years.
 No association has been found between age of
onset and severity or disability.
ET- Disability
85% percent of individuals with ET
report significant changes in their
livelihood and socializing.
15% percent report being seriously
disabled by ET.
 Decreased quality of life results from both loss of
function and embarrassment. In a study of
hereditary ET, 25% changed jobs or took early
retirement; 65% did not dine out; 30% did not
attend parties, shop alone, partake of a favorite
hobby or sport, or use public transportation; and
20% stopped driving.
 An estimated 0.5-11.1% of affected individuals seek
medical attention
ET- Genetics
 ET is familial in at least 50-70% of cases.
Transmission is autosomal dominant, with
incomplete penetrance. Some cases are sporadic
with unknown etiology.
 Two susceptibility loci have been found;
 The FET1 gene is located at 3q13 and was
identified in 75 members of 16 Icelandic families.
 ETM2 gene at 2p25-22, was identified in 15 members of 4
generations of Americans.
ET-pathophysiology
Two neural circuits have been proposed to
explain the pathophysiology of tremor.
1. A basal ganglia-thalamocortical motor loop
involving the globus pallidum, anterior VL
thalamic nucleus, and supplementary
motor area may be affected in
extrapyramidal tremor diseases such as PD
and ET.
2. Another loop, involving the cerebellum,
posterior VL thalamic nucleus, and motor
cortex, may explain tremor of other
etiologies (eg, cerebellar tremor).
Treatment:
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Propranolol
Primidone
Clozapine
Gabapentin
Benzodiazepines
Topamax
BTX-A
Definition:
Dystonia is a movement disorder
characterized by sustained muscle
contractions that frequently cause
twisting or repetitive movements and
abnormal, sometimes painful,
postures or positions
Classification :
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Etiology
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primary
secondary
Distribution of body regions affected
Age of onset
Etiology:
Primary
 Dystonia the single sign
 History,clinical and laboratory findings are
normal
 Usually action dystonia
Secondary
 Associated with hereditary neurological
diseases
 Environmental (birth trauma or drug use)
 Psychogenic dystonia
Distribution of body:
Focal
 Blepharospasm, cervical, laryngeal, hand.
Segmental
 Meige, OMD
Multifocal
 Different types
Hemidystonia
 Vascular or CP
Generalized
 Torsion dystonia
 Dopa responsive dystonia
Age of onset:
Pathophysiology:
 Is not known
 Reduced inhibition at various levels of
motor system
 Sensory motor disintegration of BG
and motor cortex.
 Alteration of discharge rate in GPI
Treatment :
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Levodopa and dopamine agonists
Anticholinergics
Clonazepam
Baclofen
Atypical neuroleptics
Tetrabenazine
Botulinum toxin type A ( Botox,
Dysport)
BOTULINUM TOXIN TYPE A
(BTX-A)
BTX-A acts as presynaptically at nerve
terminals to prevent release of
acetylcholine.
CHEMICAL DENERVATION
Dimention coefficient
19s
16s
12s
7s
Molecular weight (kdaltons)
900
500
300
150
haemagglutinin
Non-toxic protein
neurotoxin
LL
Toxin type
Complexes
A
LL,L,M,S
B
L,M,s
C1
L,M,S
L
D
L,M,S
M
S
E
F
M,S
M,s
G
7
Sites of action of BTX-A
 Alpha motor neuron
 (Neuro-muscular junction)
 Gamma motor neurons
 (Muscle spindles)
 Autonomic nervous system
 (Cholinergic nerve endings)
 C and A delta fibers
 Central nervous system?
Clinical Applications of BTX-A
 Focal Dystonias
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Blepharospasm (lid “apraxia”)
Oromandibular-facial-lingual dystonia
Cervical dystonia (torticollis)
Laryngeal dystonia (spasmodic dysphonia)
Task-specific dystonia (occupational cramps)
Other focal dystonias (Idiopathic, secondary)
 Other Involuntary Movements
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 Other Inappropriate
Contractions
Voice,head and limb tremor
Palatal myoclonus
Hemifacial spasm
Tics
 Other Applications
 Protective ptosis
 Essential hyperhidrosis
 Cosmetic (wrinkles, facial asymmetry)
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Strabismus
Nystagmus
Myokymia
Bruxism (TMJ)
Stuttering
Painful rigidity
Muscle contraction headaches
Lumbosacral strain and back
spasms
Radiculopathy with secondary
muscle spasms
Spasticity (CP included)
Spastic bladder
Achalasia (esophageal)
Pelvirectal spasms
(anismus,vaginismus)
BTX-A Side Effects
 Over Weakness
 Local Pain
 Blue Spots
 Distant Effects - Rare
 Lost of Efficacy
CHOREOATHETOSIS
 Chorea (dance) - irregular, rapid, uncontrolled,
involuntary,excessive dyskinetic movements.
 Athetosis (not fixed) - slow,sinuous writhing
movements especially in the hands.
 Ballismus- a form of chorea with large
amplitude of the affected extremity.
Chreoathetosis seems to result from
damage of indirect pathways of the BG.
These indirect pathways normally inhibit
the unwanted movements.
Etiology
 Vascular
 Immune mediated
 Sydenham’s chorea
 CP
 Metabolic
 Hereditary
 Huntington disease
 Wilson disease
HUNTINGTON DISEASE
Age 35-50 years
Rare (4-10/105)
Autosomal dominant- chromosome 4 , mutation of
IT15 gene  repeats of amino acids (CAG) 
abnormal huntingtin (genetic anticipation,
paternal)
Degenerative changes in caudate nucleus and
putamen (spiny neurons and GABA)
Mitochondrial dysfunction  excessive activation
and exitotoxicity of glutamate  apoptosis .
Clinical manifestations:
 Behavioral, emotional and psychiatric
disturbances.
 Cognitive decline
 Motor disturbances
 Chorea
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postural instability
difficulty swallowing
dysarthria
motor impersistance
Treatment:
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Neuroleptics
BD
TBZ
Riluzole
Coenzyme Q10
WILSON DISEASE
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Autosomal recessive
Frequency 1/105
Age 10-20 years
ATP7B gene , chromosome 13
Defect in transport of
copper(ceruloplasmin)
Clinical manifestations:
 Non neurological
 Kayser-Fleischer ring
 Cirrhosis
 Neurological
 Tremor, chorea,dysphagia,dysarthria, parkinsonism,
hyperreflexia.
 Psychiatric
 From agitation to schizophrenia
Laboratory investigation:
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Low ceruloplasmin and copper in serum
Urine copper is high
Liver enzymes and liver biopsy
Normal CT or MRI of brain
Treatment :
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D-penicillamine amine (care pyridoxine)
Trientine or tetrathiomolybdate
Zinc
Diet (cocoa, chocolate, liver, mushroom,
nuts, shellfish)
TICS AND TOURETTE
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Tics are involuntary movements or sounds
Motor and vocal , simple or complex
Non rhythmic and repetitious
Sporadic and sudden
 Simple motor- fast , brief involve one or
some muscles.
 Complex motor- sequent and simultaneous
movements, produce as purposeful
movements
 Simple vocal-solitary meaningless
sounds and noise, as sniffing, throat
clearing, humming or coughing
 Complex vocal-meaningful utterances
and and verbalizations as partial or
complete words and repeated,
coprolalia, echolalia and palilalia
Spectrum of tic disorders:
 Transient tic disorder
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Childhood and adolescence
Four times boys more than girls
Motor and or vocal tics
Maximum one year
 Chronic single or multiple tic disorder
 Motor or vocal not both
 More than one year
TOURETTE’S SYNDROME
(TS)
 Genetic, childhood onset ( 1-20 years)
 Motor and vocal tics
 Accompanied with ADHD (80%), OCD, poor
impulse control, anxiety, mood disorders
and behavior disturbances (20%)
 Males > female (4:1)
 Affect 0.1- 0.3 of general population
 No definitive diagnostic test
Etiology of TS
 Is not known, 80% is genetic
 Synaptic neurotransmission?
 Disinhibition of striatal-thalamic-cortical
circuitry
 Environmental factors
 PANDAS?
Treatment
 Neuroleptic agents(antagonists and
depletors)
 Antidepressants
 Antianxiety
 BTX
MYOCLONUS
Definition:
Sudden, brief, shock-like movements
which can be positive or negative
(asterixis or flapping tremor).
Anatomic :
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cortical
subcortical
spinal
peripheral (HFS)
Etiologic:
 physiologic
 essential  progressive myoclonic
epilepsy
 secondary  drugs, nocturnal,
psyhogenic, myoclonus dystonia,
neurodegenerative, trauma, opsoclonus
– myoclonus
Treatment :
 Antiepileptics
 Benzodiazepines
 BTX-A
TARDIVE DYSKINESIA
(TD)
Sigwald (1959) first described TD
 Involuntary movements typicallly of orobuco- lingual muscles ,but any muscle in
the body can be involved related to
antipsychotic drugs.
 Mean prevalence 25%
 Annual incidence rate-5%in young and 12%
in elderly.
Mechanism:
 hypersensitivity and excessive function of
dopaminergic neurotransmitters in BG.
 High risk- young, female, affective
disorders, poor treatment response to
neuroleptics, dose duration and type of
drug holidays or interruption or increase
dose (mask TD) , anticholinergics, lithium,
parkinsonism.
Treatment of TD:
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Vit E
Valproic acid
Clonazepam
Propranolol
Ca channel blockers
Dopamine agonists
Atypical neuroleptics
Dopamine Depletor- Tetrabenazine
Tetrabenazine (Xenazine ,Nituman)
 Has two modes of action:
1- blocking postsynaptic dopamine receptors
2- depleting dopamine stores in presynaptic
vesicles
 reduced transmission along dopamine
pathways.
 Depleting stores of biogenic amines:
 e.g., serotonin, noradrenaline, as well as
dopamine
 binds to vesicular monoamine transporter 2
(VMAT2)
 VMAT2 found primarily in the CNS.
Vesicular monoamine
transporter 2 (VMAT2)
Dopamine
Presynaptic
vesicle
VMAT2
2H+
Most common side effects:
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Drowsiness/fatigue
Parkinsonism
Depression
Nervousness/anxiety
Akathisia
Nausea/vomiting