Movement Disorders

1. Movement Disorders K. Zárubová

2. Movement disorders • MD - abnornal involuntary movements • dysfunction of basal ganglia (anatomically) • dysfunction of extrapyramidal motor system (functionally)

3. 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

4. Basal ganglia

5. 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)

6. Dopaminergic pathways • functional balance • cooperation of direct and indirect nigro-striatal pathways

7. Parkinsonism, parkinsonian syndrome • Parkinsonism - clinical syndrome, caused by lesion in the basal ganglia • Hypokinesia, bradykinesia • rigidity • rest tremor • postural disturbance

8. 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)

9. 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)

10. 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

11. Clinical features of PD • Early symptoms may be so mild, that a clinacal diagnosis is not possible. • Cardinal signs: • resting tremor • rigidity • bradykinesia, hypokinesia

12. 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)

13. Clinical features of PD • Other motor signs: • micrographia, masked facies, absence of associated movements (lack of armswing), quiet and monotonous speech,

14. 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)

15. 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 !

16. Parkinson’s diseaseLong-term complications Motor fluctuations („off-time“, „on-time“) Dyskinesias (uncontroled movements, chorea) Psychiatric symptoms (visual hallucinations)

17. 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)

18. 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)

19. 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

20. 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)

21. 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)

22. Vascular Parkinsonism • Subcortical arteriosclerotic encephalopathy - white matter lesions (WML) - periventricular lesions cause typical phenotypes of VP

23. 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

24. Extrapyramidal syndromes Hyperkinetic syndroms - tremor - chorea - dystonia - myoklonus - tic

25. 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

26. 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

27. Essential tremorclinical picture functional impairment • handwriting • eating and drinking • hand movements (fine crafts, dressing, …) • social embarrassment

28. 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

29. 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

30. 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

31. Myoclonus • Definition: short synchronous monophasic muscle jerks (agonists and antagonists in the same region), of irregularfrequency and amplitude • Classification: • epileptic - non-epileptic • according to distribution of signs: • focal • segmentary • generalised • according to source: • cortical • subcortical (reticular, brain-stem) • spinal (propriospinal)

32. 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