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 n Akinetic-rigid syndrome: reduction of spontaneous activity, increase of muscle tone, (akinesia/hypo/bradykinesia, rigidity) n 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 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 ( s ignificat 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 l the most frequent cause of pathological tremor, the most frequent extrapyramidal disorder n prevalence in 1-4% of population (up to 20% above 65 yrs) è 20 times more frequent than Parkinson’s disease (!) l postural tremor ! l chronical, slowly progressive course

Essential tremor clinical picture functional impairment l handwriting l eating and drinking l hand movements (fine crafts, dressing, …) l 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/ (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