Presentation on theme: "HYPERKINETIC SYNDROMES"— Presentation transcript:
1 HYPERKINETIC SYNDROMES SAMIH BADARNYParkinson and other movement disorders clinicNeurology DepartmentCarmel Medical Center- Haifa
2 TREMORDefinition:Oscillatory , usually rhythmical and regular movements affecting one or more body parts.Usually caused by alternating contraction of agonist and antagonist muscles
3 Classification by state of activity Rest Tremor: is present when a limb is fully supported against gravity and the relevant muscles are not voluntarily activated.Action tremor: occurring during any voluntary muscle contraction which includes postural, kinetic, isometric and task specific tremors.Postural tremor: is apparent during thevoluntary maintenance of a particular posturewhich is opposed by the force of gravity.
4 Kinetic tremor: is evident during any type of movement.Intention or terminal tremor: is thepronounced exacerbation of kinetic tremortowards the end of a goal directed movement.Task specific tremor: only occurs during theperformance of a highly skilled activity
5 Isometric tremor: Occurs when a voluntary muscle contraction is opposed by a rigid stationary object.Orthostatic tremor: A 14-16Hz tremor that appears afew seconds after standing and subside on sitting orwalking
6 Classification by etiology: Physiological and enhanced physiological:Present at action.Is more pronounced during periods of fatigue fear or excitement.Results from numerous factors including the heartbeat, low pass filtering properties of striatedmuscles, motor neurons firing andsynchronization by spindle feed back.
7 Parkinsonian tremor:Slow 3-5 Hz rest tremor (pill rolling) involving the limbs and/or tongue chin and lips.May be asymmetrical.May be accompanied by postural(“re-mergent”) tremor.
8 Dystonic Tremor:A jerky irregular action tremor intermingled with sustained muscular spasms that can last several seconds.May involve the muscles of the neck (tremulous spasmodic torticollis), face (orofacial dyskinesia), trunk and limbs.
9 Midbrain (“rubral”, “Cerebellar outflow”) tremor: A tremor which is present at rest, worse onposture and is further exacerbated by movement.This type of tremor is most commonly seen inMS and brainstem vascular lesions.Cerebellar Tremor:A kinetic tremor with marked intentional component.The tremor is usually accompanied by disorders of ocular motility ( dysmetria, nystagmus) incordination, DDK pendular reflexes and unsteady gait.
10 ESSENTIAL TREMOREssential tremor (ET) is the most common movement disorder. It is a syndrome characterized by a slowly progressive, rapid (4-12Hz), postural and/or kinetic tremor, usually affecting both upper extremities.
11 Epidemiology The estimated prevalence of ET is 0.3- 5.6% of the general population.Both sexes are affected equally although headtremor may be more frequent in women.The prevalence of ET increases with age.Age of onset has bimodal peaks - one in lateadolescence to early adulthood and a second inolder adulthood. The mean age at presentation is35-45 years.No association has been found between age ofonset and severity or disability.
12 ET- Disability85% percent of individuals with ET report significant changes in their livelihood and socializing.15% percent report being seriously disabled by ET.
13 Decreased quality of life results from both loss of function and embarrassment. In a study of hereditary ET, 25% changed jobs or took earlyretirement; 65% did not dine out; 30% did not attend parties, shop alone, partake of a favorite hobby or sport, or use public transportation; and 20% stopped driving.An estimated % of affected individuals seek medical attention
14 ET- GeneticsET is familial in at least 50-70% of cases. Transmission is autosomal dominant, with incomplete penetrance. Some cases are sporadic with unknown etiology.Two susceptibility loci have been found;The FET1 gene is located at 3q13 and wasidentified in 75 members of 16 Icelandic families.ETM2 gene at 2p25-22, was identified in 15 members of 4generations of Americans.
15 ET-pathophysiologyTwo neural circuits have been proposed to explain the pathophysiology of tremor.A basal ganglia-thalamocortical motor loop involving the globus pallidum, anterior VL thalamic nucleus, and supplementary motor area may be affected in extrapyramidal tremor diseases such as PD and ET.Another loop, involving the cerebellum, posterior VL thalamic nucleus, and motor cortex, may explain tremor of other etiologies (eg, cerebellar tremor).
17 Definition:Dystonia is a movement disorder characterized by sustained muscle contractions that frequently cause twisting or repetitive movements and abnormal, sometimes painful, postures or positions
18 Classification : Etiology Distribution of body regions affected primarysecondaryDistribution of body regions affectedAge of onset
19 Etiology: Primary Secondary Dystonia the single sign History,clinical and laboratory findings are normalUsually action dystoniaSecondaryAssociated with hereditary neurological diseasesEnvironmental (birth trauma or drug use)Psychogenic dystonia
20 Distribution of body: Focal Blepharospasm, cervical, laryngeal, hand. SegmentalMeige, OMDMultifocalDifferent typesHemidystoniaVascular or CPGeneralizedTorsion dystoniaDopa responsive dystonia
30 Sites of action of BTX-A Alpha motor neuron(Neuro-muscular junction)Gamma motor neurons(Muscle spindles)Autonomic nervous system(Cholinergic nerve endings)C and A delta fibersCentral nervous system?
32 BTX-A Side Effects Over Weakness Local Pain Blue Spots Distant Effects - RareLost of Efficacy
33 CHOREOATHETOSISChorea (dance) - irregular, rapid, uncontrolled, involuntary,excessive dyskinetic movements.Athetosis (not fixed) - slow,sinuous writhing movements especially in the hands.Ballismus- a form of chorea with large amplitude of the affected extremity.
34 Chreoathetosis seems to result from damage of indirect pathways of the BG. These indirect pathways normally inhibit the unwanted movements.
39 WILSON DISEASE Autosomal recessive Frequency 1/105 Age 10-20 years ATP7B gene , chromosome 13Defect in transport of copper(ceruloplasmin)
40 Clinical manifestations: Non neurologicalKayser-Fleischer ringCirrhosisNeurologicalTremor, chorea,dysphagia,dysarthria, parkinsonism, hyperreflexia.PsychiatricFrom agitation to schizophrenia
41 Laboratory investigation: Low ceruloplasmin and copper in serumUrine copper is highLiver enzymes and liver biopsyNormal CT or MRI of brain
42 Treatment : D-penicillamine amine (care pyridoxine) Trientine or tetrathiomolybdateZincDiet (cocoa, chocolate, liver, mushroom, nuts, shellfish)
43 TICS AND TOURETTE Tics are involuntary movements or sounds Motor and vocal , simple or complexNon rhythmic and repetitiousSporadic and suddenSimple motor- fast , brief involve one or some muscles.Complex motor- sequent and simultaneous movements, produce as purposeful movements
44 Simple vocal-solitary meaningless sounds and noise, as sniffing, throat clearing, humming or coughingComplex vocal-meaningful utterances and and verbalizations as partial or complete words and repeated, coprolalia, echolalia and palilalia
45 Spectrum of tic disorders: Transient tic disorderChildhood and adolescenceFour times boys more than girlsMotor and or vocal ticsMaximum one yearChronic single or multiple tic disorderMotor or vocal not bothMore than one year
46 TOURETTE’S SYNDROME (TS) Genetic, childhood onset ( 1-20 years)Motor and vocal ticsAccompanied with ADHD (80%), OCD, poor impulse control, anxiety, mood disorders and behavior disturbances (20%)Males > female (4:1)Affect of general populationNo definitive diagnostic test
47 Etiology of TS Treatment Is not known, 80% is genetic Synaptic neurotransmission?Disinhibition of striatal-thalamic-cortical circuitryEnvironmental factorsPANDAS?TreatmentNeuroleptic agents(antagonists and depletors)AntidepressantsAntianxietyBTX
48 MYOCLONUS Definition: Anatomic : Sudden, brief, shock-like movements which can be positive or negative (asterixis or flapping tremor).Anatomic :corticalsubcorticalspinalperipheral (HFS)
51 TARDIVE DYSKINESIA (TD) Sigwald (1959) first described TDInvoluntary movements typicallly of oro-buco- lingual muscles ,but any muscle in the body can be involved related to antipsychotic drugs.Mean prevalence 25%Annual incidence rate-5%in young and 12% in elderly.
52 Mechanism:hypersensitivity and excessive function of dopaminergic neurotransmitters in BG.High risk- young, female, affective disorders, poor treatment response to neuroleptics, dose duration and type of drug holidays or interruption or increase dose (mask TD) , anticholinergics, lithium, parkinsonism.
53 Treatment of TD: Vit E Valproic acid Clonazepam Propranolol Ca channel blockersDopamine agonistsAtypical neurolepticsDopamine Depletor- Tetrabenazine
54 Tetrabenazine (Xenazine ,Nituman) Has two modes of action:1- blocking postsynaptic dopamine receptors2- depleting dopamine stores in presynaptic vesicles reduced transmission along dopaminepathways.Depleting stores of biogenic amines:e.g., serotonin, noradrenaline, as well as dopaminebinds to vesicular monoamine transporter 2 (VMAT2)VMAT2 found primarily in the CNS.