Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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 -„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. 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