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

– 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 -„Parkinson-

plus“ 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.

 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
 the most frequent cause of pathological tremor, the most
frequent extrapyramidal disorder
 prevalence in 1-4% of population (up to 20% above 65 yrs)
 20 times more frequent than Parkinson’s disease (!)

 postural tremor !
 chronical, slowly progressive course
 Essential tremor
clinical picture

functional impairment
 handwriting
 eating and drinking
 hand movements (fine crafts, dressing, …)
 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
• 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