Transcript Extrapyramidal system

Movement Disorders
K. Zárubová
Movement disorders
• MD - abnornal involuntary movements
• dysfunction of basal ganglia (anatomically)
• dysfunction of extrapyramidal motor
system (functionally)
Extrapyramidal system
• The Basal Ganglia include the:
– Striatum (caudate nucleus and
putamen)
– Globus pallidus int. and ext.
– Subthalamic nucleus
– Substantia nigra (pars reticulata, pars
compacta)
– Intralaminar nuclei of thalamus
Basal ganglia
Classification of extrapyramidal
syndromes
 Akinetic-rigid syndrome:
• reduction of spontaneous activity, increase of
muscle tone, (akinesia/hypo/bradykinesia,
rigidity)
 Hyperkinetic syndromes:
• involuntary and irregular movements
(tremor, chorea, balismus, dystonia, myoclonus,
tic)
Dopaminergic pathways
• functional balance
• cooperation of direct and
indirect nigro-striatal
pathways
Parkinsonism,
parkinsonian syndrome
• Parkinsonism - clinical syndrome, caused
by lesion in the basal ganglia
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Hypokinesia, bradykinesia
rigidity
rest tremor
postural disturbance
Causes of parkinsonism
 Primary (idiopathic) Parkinson s Disease
(PD). PD makes up approximately 80% of cases
of parkinsonism
 Secondary parkinsonism (associated with
infectious agents, drugs, toxins, vascular
disease, trauma, brain neoplasm)
 Neurodegenerative disorders -„Parkinsonplus“ syndromes (MSA, PSP)
Parkinson‘s disease (PD)
• The condition was first described by
James Parkinson in 1817 (paralysis
agitans)
• Most cases of PD start between 50-70 y.
(peak age of onset in the 6. decade,
young onset before 40y.)
• Prevalence: 160 cases per 100,000
population,
• (increase with age)
Parkinson s disease (PD)
pathology
• progresive degeneration (loss) of dopaminergic
neurons in substantia nigra, projecting to the striatum
• resulting in decreased level of dopamine (inbalance in
the neurotransmitter mechanism)
• symptomes of PD appear when about 70% of
nigrostriate dopamine neurones are lost
• presynaptic lesion !
• postsynaptic dopaminergic receptors D2 are intact
• response to dopaminergic therapy - levodopa - is
preserved
Clinical features of PD
 Early symptoms may be so mild, that a clinacal
diagnosis is not possible.
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Cardinal signs:
resting tremor
rigidity
bradykinesia, hypokinesia
Cardinal signs
 Resting tremor – worse in a rest and decrease
during movement
 Rigidity – resistance to passive movement about
a joint, (cogwheel)
 Bradykinesia – refers to slowness of movement
and decrease amplitude of movement
 Postural instability - refers to inbalance (freezing,
propulsion and festination)
Clinical features of PD
 Other motor signs:
 micrographia, masked facies, absence of
associated movements (lack of armswing),
quiet and monotonous speech,
Clinical features of PD
 Non-motor signs:
 Autonomic dysfunction (obstipation, urinary,
sexual, orthostatic hypotension, seborrheic
dermatitis, increased sweating, drooling)
 Sleep disturbances
 Mental and psychiatric problems (depression,
cognitive dysfunction, demetia)
Parkinson s disease (PD)
diagnosis
• The diagnosis is based on the presence of
cardinal clinical signs and the response to
dopaminergic therapy
• The best clinical predictors of dg. PD are:
– Asymmetry (symptoms begin on one side of the body
(unilateral)
– Presence of at least 2 of 3 major signs
– Absence of a secondary cause
– Good response to dopamine replacement therapy !
Parkinson’s disease
Long-term complications
Motor fluctuations („off-time“, „on-time“)
Dyskinesias (uncontroled movements, chorea)
Psychiatric symptoms (visual hallucinations)
PD - Treatment
 Basic symptomatic therapy:
 L-DOPA (natural precursor of dopamine),
 Dopamine agonists (ropinirol, pramipexol, rotigotin)
 Additional symptomatic therapy:
 COMT inhibitors (entacapon)
 MAO-B inhibitors (Selegiline)
 (Anticholinergics)
 Amantadine
 Surgical therapy
 Deep brain stimulation (DBS)
PD - Treatment
• Levodopa – standard of symptomatic treatment
– provides the greatest antiparkinsonian benefit
• Dopamine agonists can be used as:
– initial symptomatic therapy in early disease provide good benefit but lack sufficient
efficacy to control signs in later disease
– may control late onset complications
(significat effect on the reduction of
dyskinesias)
PD - Treatment
• COMT inhibitors – (entacapon) prolong the
effectiveness of a dose of levodopa by preventing
its breakdown
– to decrease the duration of „off-time“
• MAO-B inhibitors (selegilin)– slow the breakdown
of dopamin in the brain
Secondary parkinsonian syndrome
Secondary parkinsonism
 drugs- induced
 multiinfarct encephalopathy
 normotension hydrocephalus
Neurodegenerative disorders
Atypical parkinsonism - „Parkinson-plus“
syndromes
 Multisystem atrophy (MSA)
 Progressive supranuclear palsy (PSP)
Drug-induced parkinsonian syndrome
mechanisms
– DA receptor blockade in the striatum
• Classical neuroleptics
(haloperidole, chlorpromazine, levopromazine,
prochlorperazine, perfenazine, etc., all depot neuroleptics)
• metoclopramide (Cerucal, Degan, Paspertin)
Vascular Parkinsonism
• Subcortical arteriosclerotic encephalopathy
- white matter lesions (WML)
- periventricular lesions
cause typical
phenotypes of VP
Clinical signs of
vascular parkinsonism
• Predominant involvment of the legs = („lower-body
parkinsonism“)
– gait and balance disorder (frontal type gait, apraxia of gate,
shuffling, short steps)
– tremor is usually absent
• No response to levodopa
• usually additional features: pseudobulbar palsy, pyramidal
signs, cognitive disturbances
Extrapyramidal syndromes
Hyperkinetic syndroms
- tremor
- chorea
- dystonia
- myoklonus
- tic
Tremor - classification
• rest tremor
– Parkinson‘s disease
• postural tremor
– physiologic tremor
– enhanced physiologic tremor
– essential tremor !!
• kinetic tremor
– cerebellar tremor
– Wilson’s disease
– Holmes’ ("rubral“) tremor
Essential tremor
epidemiology
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the most frequent cause of pathological tremor, the most
frequent extrapyramidal disorder
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prevalence in 1-4% of population (up to 20% above 65 yrs)
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20 times more frequent than Parkinson’s disease (!)
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postural tremor !
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chronical, slowly progressive course
Essential tremor
clinical picture
functional impairment
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handwriting
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eating and drinking
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hand movements (fine crafts, dressing, …)
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social embarrassment
Chorea
• Definition:
irregular, random movements of body parts, usually quick,
twisting, with distal predominance
• Structural involvement:
striatum (ncl. caudatus, putamen)
• Pharmacological mechanism:
hyperdopaminergic
• Standard pharmacological treatment:
neuroleptics
Chorea
can occur in a variety of conditions and disorders
• primary feature of Huntington s disease, other
progressive neurological disorders
may be caused:
• by drugs (levodopa, anti-psychotics)
• by metabolic disorders, endocrine disorders,
vascular leasions
Dystonia
• Definition:
sustained muscle contractions producing twisting and
repetitive movements or abnormal postures of affected body
parts
• Structural involvement:
striatum, pallidum, thalamus, their connections
• Pharmacological mechanism:
hypercholinergic
hypodopaminergic (DRD)
• Standard pharmacological treatment:
anticholinergics
Myoclonus
•
Definition:
short synchronous monophasic muscle jerks (agonists and
antagonists in the same region), of irregular frequency and
amplitude
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Classification:
– epileptic - non-epileptic
– according to distribution of signs:
• focal
• segmentary
• generalised
– according to source:
• cortical
• subcortical (reticular, brain-stem)
• spinal (propriospinal)
Tic
• Gilles de la Tourette syndrome
• prevalence  50/100 000 (with associated behav. disorders, up
to 1/100)
• combination of motor and vocal tics
• beginning in childhood (95% before 12 yrs), M:F 3-4:1
• associated behavioral disorders (attention deficit hyperactivity
disorder, obsessive-compulsive disorder and impulsiveness)
• genetic predisposition + environmental factors
• Transient tic disorder
• prevalence up to 24/100 school children
• duration  12 months