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 diseaseLong-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 disordersAtypical 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 tremorclinical 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