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  • 1. Update ofdystoniaDR/ AYMAN AL-MALTASSISTANT LECTURER NEUROLOGY
  • 2. • Defintion of spectrum of movement disorder anddystonia• Classification of dystonia
  • 3. Movement disorders• Disturbance in speed or fluency of voluntarymovementor• the presence of unintended extra movement• Extrapyramidal diseases• Hyperkinetic excessive amount of spontanous motoractivity and abnormal involuntary move occur• Hypokinetic Cx by akinesia or bradykinesia in whichpurposeful motor activity is absent or reduced.
  • 4. Movement Disorders• Clinically, divided into 2 categories– Poverty of movement (Akinesia)• Associated with an increase in muscle tone– Excessive abnormal involuntary movements(Dyskinesia)• Classified as tremor, chorea, ballism, dystonia,athetosis, myoclonus, and tic.
  • 5. The spectrumBallismus DystoniaChorea AthetosisMovements become - Less violent / explosive / jerky- Smoother and more flowing- More sustainedThey differ from tics in that they cannot be suppressed byvoluntary controlMyoclonus6
  • 6. Basal ganglia• Basal ganglia regulate the initiation , scalingand control of the amplitude and direction ofmovement• Movement disorders arise from biochemicalor structural abnormalities in thesestructures.
  • 7. ..conduring an intended /projected movement oneset of activities is facilitated all the other aresurpassed.• BRAKE prevents the target structures fromgenerating unwanted motor activity• Switch selects which of the many availablewill be activated at any given time
  • 8. Definition of dystonia• Oppenheim(1911) : “dystonia musculorumdeformans”, a syndrome in children with twistedposture, muscle spasms, bizarre walking &progression of symptom, leading to sustained fixedpostural deformity.• Flatau & Sterling(1911) : inherited disease &progressive torsion spasm• Derek Denny-Brown(1964) : a fixed or relativelyfixed attitude.• Fahn et al (1987) : a syndrome of sustained musclecontractions, fequently causing twisting & repetitivemovements, or abnormal postures
  • 9. Features of dystonic movements(I)• Speed : from slow to rapid, more often the latter* myoclonic dystonia : so fast, prolonged burst onEMG* myoclonus : short duration burst on EMG• Aggravated by voluntary movement, stress,emotional upset , fatigue* Action dystonia : dystonic movement withvoluntary movement* Task specific dystonia : writer’s cramp,musician’s cramp, chewing, speaking.
  • 10. Features of dystonic movements• Relieved by relaxation, hypnosis & sleep* diminished by tactile or proprioceptive “sensorytrick” (geste antagoniste).- Torticollis: hand on the chin or side of face .- Oro-lingual dystonia: Touching the lips orplacing an object in the mouth.• paradoxical dystonia : for dystonia at rest to beimproved by active movement; chewing alleviatesblepharospasm.• Spreading to contiguous body parts: the younger theonset, the more likely.
  • 11. Features of dystonic movements• Pain : uncommon* except cervical dystonia : 75 % of Pts of cervicaldystonia• “Dystonic storms” : a crisis of sudden markedincrease in severity• Lead to rhabdomyolysis & myoglobinuria:admission to ICU
  • 12. Features of dystonic movements• Ipsilateral overflow dystonia (IOFD):involuntrymovement of muscles adjacent to those involved indystonia.• Contralateral OFD: dystonic movement in normalcontralateral limb during dystonic movement orposture of limb 1ry involved by dystonia• Mirror dystonia: dystonic movement induced byspecific task like writing done by opposite homologusnormal body part.
  • 13. Classification of dystonia• Age at onset• Distribution• Etiology
  • 14. Classification by age at onsetAge most important single factor a/w prognosis of primarydystonia. the younger age at onset, the more severe & the morespread of dystonia.Childhood-onset (0-12 yrs)• most often hereditary : probably autosomal dominant withincomplete penetrance.• progress to generalized type.Adolescent-onset (13-20 yrs).Adult-onset(> 20 yrs).• most often sporadic, remain focal type(no progress togeneralized type)
  • 15. Classification by distributionFocal dystonia• blepharospasm, torticollis, oromandibular dystonia,spastic dysphonia, writer’s cramp.Segmental dystonia• dystonia in the two or more contiguous body parts .• e.g. Cranial+brachial, cranial+axial,cranial+cervical(Meige syndrome)Generalized dystonia• Involves several areas on both sides of the body• a combination of leg involvement plus involvementof any other area of the body
  • 16. Classification by distributionMultifocal dystonia• two or more noncontiguous parts of the bodyHemidystonia• affect one-half of the body• symptomatic rather than primary
  • 17. Classification by Etiology(I)1- Primary dystonia(ITD, dystonia musculorum deformans)• no known underlying brain lesion• hereditary & idiopathic form• the only neurologic abnormalities : dystonia2- secondary dystonia
  • 18. 1- Primary dystoniaChildhood and adolescent onset• DYT1: AD with reduced penetrance (~30%), earlylimb onset with predominant family phenotype•Adult onset• DYT7: AD, cervical onset in adults.Mixed phenotype• DYT6, DYT 13: AD, early and late onset with possiblecranial, cervical, and sometimes limb onset andvariable spread Other genes to be identified
  • 19. Idiopathic torsion dystonia DTY1• Dystonia without any other abnormal involuntarymovement• usually starts in childhood & in limbs.• AD with reduced penetrance (30-40 %).• Gene : DYT1, chromosome 9q34 in non-jewish &Ashkenazi JewishCaused by a GAG deletion in theTorsin A gene.• Late-onset DTY6, cervical cranial-cervical onset :genetic heterogeneity.• DYT1 Variable phenotype - may present only withwriters cramp.
  • 20. Early-onset Late-onset< 15 yrs > 20 yrsfrequently onset in leg focal onset(cranial)commonly generalized remain focalusually hereditary usually sporadicDTY1 DYT7Responds well to globus pallidus stimulation.DYT6 : Later onset than DYT1, with dysphonia.Check for this if DYT1 is negative, or cranio-cervicalonset.
  • 21. Ashkenazi Non-JewishMode ofinheritance100 % AD 85% ADPenetrance 30 409q haplotype Yes NoGAG TOR1Adeletion90 40-65Age of onset>40rare 10-15incidence 1/6000-1/2000 1/160,000% new mutation Rare 14DYT1 Features in Ashkenazi andNon-Jewish Populations
  • 22. Idiopathic torsion dystonia(II)• Onset : in 4th to 6th decades• foci in the axial skeletal muscles(cranium and neck), rarelygeneralized• insidious onset , gradual progression in the first few years• Symptoms Blepharospasm: rapid blinking of the eyelids Torticollis (wryneck):turning of the head to one side (trapeziusand sternocleidomastoid) Spasmodic dysphonia: strained or breathy speech Oromandibular dystonia: involuntary jaw opening/closingand tongue movement "Writers Cramp": a dystonia affecting the hand and armmuscles, usually occurring with intended movement(adult type)
  • 23. BlepharospasmBilat, synchronous the involuntarycontraction of the eyelids, leading touncontrollable blinking and closure of theeyelids. women> men 6thdecade, functional blindnessAggravated by watching TV, readigRelieved by touching eyelidSpasm remain focal or spread to OM areaMeige syndrome, Bruegel disease
  • 24. Blepharospasm• the first symptom to appear is an increased rate ofblinking .• uncontrollable squinting/closing of eyes• light sensitivity(photophobic)• squinting/eyes closing during speech• uncontrollable eyes closing shut (rare instancescompletely causing blindness)• In addition, in some patients, the dystonic spasms maysometimes be provoked by certain activities, such astalking, chewing,
  • 25. The term "facial tic" is often used to describeinvoluntary movements that involve the face,particularly those around the eyes and the corner of themouth. These movements are usually brief and notsustained. They are usually not associated with the"squeezing" of the muscles around the eyes thattypically accompanies blepharospasmWhat is the difference between facial ticand blepharospasm
  • 26. Brueghels syndrome• Blepharospasm-oromandibular dystoniasyndrome: open mouth• A variant of adult-onset torsion dystonia?When OMD is combined with blepharospasm, Thesymptoms usually begin between the ages of 30 and 70years old and appear to be more common in womenthan in men (2:1 ratio)The incidence is about one case in 20,000 peopleMeige syndrome
  • 27. MEIGESYNDROME.flv
  • 28. Oromandibular dystonia• difficulty opening the mouth (trismus)• clenching or grinding of the teeth (bruxism)• spasms of jaw opening• sideways deviation or protrusion of the jaw• drawing back (retraction) of the corners of the mouth• deviation or protrusion of the tongue.• jaw pain, lip smackig and or tiwitches• difficulties eating and drinking• difficulties speaking (dysarthria)Part segmental
  • 29. Spasmodic dysphonia• Dystonic spasm in laryngeal muscles• 4thto 5thdecades• Adductor types :most common,strained ,highpitched associated with repetitive brief interruptionof speech,singing and whispering reduce spasm• Abduction type :whispering breathy• mixed
  • 30. Cervical dystonia• torticollis, is the most common focal dystonia.• insidious onset ,aged 30-50 years, or earlier.common women.• Intermittent spasms of the neck muscles or abnormalhead movements occur because of contractions of thesternocleidomastoid, trapezius, and posterior cervicalmuscles. This effect results in a patterned, repetitive,and spasmodic movement that causes the head totwist (rotational torticollis), extend (retrocollis), flex(anterocollis), or tilt toward the shoulder(laterocollis).
  • 31. Cervical dystoniaComplications of cervical dystoniaPain experienced by 93% ofpatientsDifficulty reading, driving,watching TVWithdrawal from socialinteractionsSpontaneous remission 10-20%not sustainedCervical Dystonia Patient Traits:Prevalence: 9/100,000Mean age of onset: 41 to 42 yrs Female: 62% to 67%Abnormal postures: 83%Head jerks/neck spasms: 62% Pain: 90%Types of postures incervical dystoniaTorticollis: 82-97%Laterocollis: 42-63%Retrocollis: 29-32%Anterocollis: 14-25%Most patients showcombination
  • 32. Neck and shoulder mm affected in cervical dystoniaSplenius capitisLevator scapulae, TrapeziusSternocleidomastoid, ScalenesLongissimus, Splenius cervicis
  • 33. Torticollis mm involvementPrimary: Ipsi splenius, contraSCMSecondary: Ipsi semispinalis,ipsi longissimus, spleniuscervicis,levator scapulae, interioroblique, longus capitisLaterocollis mmPrimary: Splenius capitis,ipsi scalenes,levator scapulae,longissimusSecondary: Splenius cervicisRetrocollis mmPrimary: Bilateralsplenius capitis,posterior vertebralsSecondary: SpleniuscervicisAnterocollis mminvolvementPrimary: BilateralSCMSecondary: Scalenecomplex
  • 34. Limb dystoniaWriter’s cramp:- Dystonic posturing of arm when hand used to performspecific tasks e.g. writing, playing pianoPaifulEqual both sexes
  • 35. Pathophysiology of 1ry dystonias• No clear neurodegenerative processes.• Abnormalities are likely subtle changes inneuronal signaling and communication.• BG implicated, with some evidence of reducedoutput from the GPi, although this iscontradicted by symptom improvementfollowing GPi lesioning.• Also evidence of cortical dysfunction andabnormal sensory afferent processing.
  • 36. Pathophysiology of 1ry dystonias• Alteration in the pattern of pallidal-thalamic activitiesduring voluntary movement and abnormal sensoryfeedback lead to an increase in abnormallysynchronous cortical output and thus co-contraction ofmultiple muscle groups or overactivation of intendedmuscle groups.• In addition, abnormal thalamic activity synchronizesthe intended movement as well as unwanted overflowmovements in other muscles
  • 37. Pathophysiology Generalised dystonia is a disorder of the CNS, thepathophysiology of acquired torticollis remainspoorly understood.The observable end result is a centrally activated(but involuntary), sustained contraction of skeletalmuscle, resulting in abnormal posture.Neurophysiological and functional imaging studieshave implicated abnormalities in the BG, as well assensory and motor cortices.There is also evidence of abnormalities in dopaminesignalling, sensory processing, cortical motorinhibition, and sensorimotor integration.
  • 38. Quantitative voxel-based morphometry studieshave shown decreased volumes of caudate,putamen, and sensorimotor cotex compared tocontrol subjects.pathogenesis of dystoniastill unclear, hypothesis: alteration in pattern ofthe pallidal-thalamic activities duringvoluntary movement + abnormal sensoryfeedback leads to abnormally synchronouscortical output
  • 39. 2- Secondary dystonia• Variety of lesions, mostly involving the BG and/ordopamine synthesis.1. Inherited nondegenerative (dystonia plus)• Dopa-responsive dystonia: due to DYT5 and othergenetic defects• Myoclonus dystonia: due to DYT11 and possiblyother genetic defects• Rapid-onset dystonia parkinsonism: due to DYT12
  • 40. 2- Secondary dystonia2. Inherited degenerative• • Autosomal dominant, autosomal recessive,X-linked (DYT3), mitochondrial3. Degenerative disorders of unknown etiology• Parkinson disease• Progressive supranuclear palsy• Corticobasal ganglionic degeneration
  • 41. 2- Secondary dystonia4. Acquired• • Drugs (dopamine-receptor blockers), other• Toxins • Head trauma• • Stroke, hypoxia• • Tumors • Peripheral injuries• • Encephalitis, infectious and postinfectious5. Other movement disorders with dystonic• Tics, paroxysmal dyskinesias (DYT8, DYT9,DYT10)6. Psychogenic Dystonia
  • 42. Classification by etiology(II)Dystonia-plus syndrome• dystonia a/w parkinsonism or myoclonus without knownneurodegeneration• DRD & myoclonic dystonia(neurochemical disorder)Heredodegenerative disease• X-linked recessive* Lubag : DYT3 gene(Xq 13), filipino male, young adult onset, cranialdystonia, parkinsonism• Autosomal dominant* Rapid-onset dystonia-parkinsonism(RDP) : adolescent & adult onset* Juvenile parkinsonism(Early-onset parkinsonism with dystonia),Huntington’s chorea, MJD, DRPLA• Autosomal recessive* Wilson’s disease, Niemann-Pick, Metachromatic leukodystrophy,Homocystinuria, Ataxia telangiectasia, Hallervorden-Spatz disease,Hartnup’s disease, Gangliosidosis, DRD
  • 43. Dopa-responsive dystonia• Onset : 5-6 years old, girls > boys• Prevalance: 0.5 to 1 per million• autosomal dominant inheritance.• Chromosome 14, point mutation in the gene forGTP(guanosine triphosphate cyclohydrolase I: rate limiting enzyme in formation oftetrahydrobioptern, cofactor of tyrosine hydroxylase& phenylalanine hydroxylase• focal dystonia, typically dystonia of lower limbsaffecting gait progress to G
  • 44. FIGURE 2.2 Diagram of GCH1defect pathway.
  • 45. Dopa-responsive dystonia• paraparesis• diurnal variation : no symptom in morning, worseat night, worsen after exertion• parkinsonian features• markedly improve with low dose levodopa(100-300)per day divided dose.* no adverse effects of response fluctuation despitelong use• Often misdiagnosed as cerebral palsy.• Phenylalnine loading test
  • 46. Phenylalnine loading test• Phenylalnine loading test: ingestion PA(100mg/kg) sampling 1ml plasma 0, 1, 2, 4,& 6 hours later Phenylalanine levels peakat 2 hrs and are markedly elevated at 4 and 6hrs compared to controls. Tyrosine levels donot increase at all increased PlasmaPhe/Tyr profile
  • 47. Juvenile PD DRD Childhood PTDonset age rare < 8 infancy to 12 uncommon < 6gender male predom. Female predom. Equalinitial Sx foot dystonia/PD leg dystonia arm or leggait disorderdiurnal no sometimes nobradykinesia present present noAnti-Ch yes yes yesresponseDopa R yes yes no or mildDopa mod to high very low highdosage“off” fluctuation uncommon unknowndyskinesia prominent uncommon unknownFluoroDopa decreased normal normalPETβCIT SPECT decreased decreased normalPhe load test normal abnormal normalPrognosis progressive plateaus usually worsen
  • 48. Rapid-onset dystonia - parkinsonism(RDP)• Autosomal dominant inheritance ch 19q13• adolescent & adult onset• Clinical features( severe worsening, bulbar)* sudden onset of dysarthria, dysphagia, severedystonic spasm, bradykinesia & postural instabilityover hours or days.( D-P-W e prominent bulbar)* progress to generalized over hours to a few weeks• normal cranial imaging• involvement of dopaminergic system : low CSF HVAconcentration• No effective tttSynonym: DYT12
  • 49. Myoclonic dystonia DYT11• MD is a distinct genetic disorder in which dystonia,usually mild and not always present, is associatedwith marked myoclonus.• There are no other neurologic signs• Autosomal dominant inheritance• mutation in the sarcoglycan gene CH 7 or 18.• onset : adolescent or early adult• dystonia & myoclonus, predominantly in arms &axial muscles
  • 50. Myoclonus dystonia. DYT11• dystonia - typically cervical / writers cramp.• The myoclonic jerks can be triggered by voluntarymovements (action myoclonus). Manifested asoverflow jerks (i.e., involving body regions notinvolved in the action perse).• The myoclonic component may respond to alcohol.• psychiatric complications, particularly OCD,anxiety, alcohol abuse• Clonazepam, valporic acid.
  • 51. Dystonia-Parkinsonism• Long-term S/E of Levodopa• Hemiparkinsonism-hemiatrophy syndrome• Lubag• Juvenile parkinsonism• DRD• Corticobasal ganglionic degeneration(CBD)• Multiple system atrophy(MSA)• Progressive supranuclear palsy(PSP)• Neuroacanthocytosis• CO poisoning
  • 52. Paroxysmal Dyskinesias• PDs are rare neurological disorders, characterized bya sudden onset of dystonic, choreatic, athetotic, andballistic movements with variable underlyingmechanisms.• The inherited paroxysmal dyskinesias, associatedwith gene loci DYT8 and DYT10, differ from theabove- described genetic dystonias insofar as thedystonic features are clinically transient.• The pathogenesic mechanisms that underlie thesefluctuating disorders await further clarification,.
  • 53. Paroxysmal nonkinesigenicdystonia/dyskinesia (PNKD)• PNKD is an AD. As its name implies, it ischaracterized by paroxysms of hyperkinesias, whichcan include dystonia, dyskinesia, choreoathetosis,and ballism.• The paroxysms are not triggered by volitionalmovements, but may be precipitated by variousfactors such as stress and alcohol.• Age of onset varies from infancy to adulthood, withadolescence being most common.• several times a day and last from minutes to hours.Scott Spasms March 28 2010.flv
  • 54. Paroxysmal kinesigenicdystonia/dyskinesia (PKD)• PKD is also AD, though sporadic cases have beenreported. There is likely significant variableexpressivity, with an apparent male predominance.• Tomita and colleagues studied several affectedJapanese families in 1999 and mapped the diseaselocus to chromosome 16. Different loci onchromosome 16 may be responsible in other affectedfamilies.• Age of onset :childhood. Seizures infancy.• triggered by sudden movement, are usually short—lasting less than a few minutes, and can occur
  • 55. Age of onset is in the first or second decade of lifechildhood or late adulthood has been reported[Demirikiran and Jankovic, 1995; Fahn, 1994].Males are more commonly affected than females with aratio of 3.75 : 1 [Fahn, 1994].Mostly, PKDs are idiopathic, and in the majority, thereis a family history of AD inheritance with penetrance >70%.Sporadic cases are reported frequently [Jankovic andDemirkiran, 2002].Some cases of PKD may be symptomatic secondary tomultiple sclerosis (MS), brain trauma or endocrinedysfunction [Bhatia, 1999].PKD Paroxysmal kinesigenic dyskinesia-PKD A New Treatment.flv
  • 56. Features of PNKD & PKDPNKD PKDChromosome 2 16Mode of inheritance AD ADAge of onset Adolescence ChildhoodTriggers Coffee, alcohol,fatigueMovementsFrequency ofattacksDAILY Hundreds/dayAssociated features Infantile seizuresResponse to AEDs Carbamazepine
  • 57. Psychogenic dystoniaClues relating to the movements• abrup onset, inconsistent movement.• incongruous movement(not fit with recognizedpattern or normal physiological pattern)• presence of additional types rhythmic shaking,bizarre gait, excessive startle, deliberate slownesscarrying out requested voluntary movement• spantaneous remission• disappear with distraction, response to placebo.• dystonia beginning as a fixed posture• presence as a paroxysmal disorder.
  • 58. Psychogenic dystoniaClues relating to the other medical observation• false weakness• false sensory complaints• multiple somatization• self-inflicted injury• obvious psychiatric disturbance• employed in the health profession or in insuranceclaims• presence of secondary gain• litigation or compensation pending
  • 59. Tardive dyskinesia tardive dystonia• meaning they have a slow or late onset• This is a common complication of long-termantipsychotic drug treatment due to dopaminereceptor antagonism. The precise mechanism isunknown, but the risk appears to increase withadvancing age or in children and infants as a sideeffect from usage of drugs for gastrointestinaldisorders.• When medication is withdrawn relatively early in apatients treatment, the dyskinesia may reverse,whereas after 6 months of exposure, the movementdisorder may persist indefinitely.
  • 60. Tardive dystonia• The clinical features of tardive dyskinesiainclude abnormal choreoathetoid movements,especially involving, in adults, the face andmouth (ie, blepharospasm, torticollis,oromandibular dystonia), and in children, thelimbs• Risk factors: old age, >6 months therapy,depot injection, genetically preclinicalparkinson
  • 61. Dystonia (cont.)• Primary Dystonia– may be due to DYT1 mutation• Secondary Dystonia– Most common cause is neurolepticadministration– Dystonia assoc. with parkinsonism– Psychogenic causes
  • 62. Dystonia (cont.)• Diagnostic Challenge: Frequent Misdiagnoses– Blepharospasm• Dry eye syndrome or tics– Cervical dystonia• Stiff neck, arthritis, subluxation of the cervicalvertebrae, posterior fossa tumors– Writer’s cramp• Carpal tunnel, strain, “tennis elbow”
  • 63. Dystonia (cont.)• Frequent Misdiagnoses (cont.)– Laryngeal dystonia• Sore throat, laryngitis, vocal abuse– Oromandibular dystonia• TMD (temporomandibular joint disorder)– All dystonia• Psychogenic, stress, nervousness
  • 64. • Investigations to consider in dystonia• FBC (inc acanthocytes), plasmacaeruloplasmin, 24 hour urinary copperexcretion and slit lamp examination, genetictesting (DYT1 in young onset), MRI brainscan, therapeutic trial of L-dopa.
  • 65. • Prognosis of dystonia• no way to predict symptoms fluctuate-stabilization is usually seen in 5 years
  • 66. Management/Treatmentwithout pain or functionalimpairment - observationwith functional impairment or painor diminished quality of life - oralmedications- physiotherapy- intramuscular botulinum toxin- physiotherapy Ongoing refractoryto therapy with botulinum toxin -deep brain stimulation- physiotherapy- radiofrequency ablation- physiotherapy- injected phenol- physiotherapy- baclofen injection via continuouspump infusion
  • 67. Treatment of dystonia(I)Physical & supportive therapy• physical therapy & brace : improve posture & prevent contracturea substitute for a “sensory trick”• muscle relaxation technique & sensory feedback therapy : adjunctDopaminergic therapy• in DRD, small dose of levodopa(100mgof levodopa with 25mg ofdecarboxylase inhibitor)* also improve with anticholinergic & carbamazepine• in Pts with idiopathic or other types of dystonia : rarely improved withdopaminergic therapyAntidopaminergic therapy• usually limited(Jankovic, 1995)• Tardive dystonia : tetrabenazine, Risperidone(D2 dopamine Rc blockingwith high affinity for 5HT2 Rc), Clozapine(D4 Rc blocking , relativelylow affinity for D2 Rc, high affinity for 5-HT2A Rc)
  • 68. Treatment of dystonia(II)Anticholinergic therapy• Trihexyphenidyl :* generalized & segmental dystonia(Jabbari, 1989)* short duration before onset of therapy : favorable response* start with 2 mg slowly increase up to 12 mg/D over next 4 weeksswitch to SR preparation* S/E : dose-related drowsiness, confusion, memory difficulty, hallucinationOther pharmacologic therapy• Benzodiazepine(clonazepam or lorazepam) : additional effect in case ofunsatisfactory anticholinergic response* clonazepam : useful for blepharospasm & with myoclonic dystonia• Baclofen : helpful for oromandibular dystonia* intrathecal baclofen : more effective in dystonia with spasticity or pain
  • 69. Treatment of dystonia(III)• Peripheral deafferentiation : somatosensory input in the pathogenesis ofdystonia* 5-10 ml of 0.5 % lidocaine• Kinesigenic paroxysmal dystonia : AED(carbamazepine, phenytoin)• non-kinesigenic paroxysmal dystonia : clonazepam, acetazolamide
  • 70. Treatment of dystonia(IV)Blepharospasm• clonazepam, lorazepam• Botox• trihexyphenidyl• orbicularis oculi myectomyOromandibular dystonia• baclofen• trihexyphenidyl• BotoxSpasmodic dysphonia• BotoxCervical• trihexyphenidyl• diazepam, lorazepam, clonazepam• Botox• tetrabenazine• carbamazepine• baclofenTask-specific dystonia(writer’s cramp)• benztropine, trihexyphenidyl• Botox• occupational therapy
  • 71. Treatment of dystonia(V)Segmental & generalized dystonia• levodopa(in child-young adults)• trihexyphenidyl, benztropine• diazepam, lorazepam, clonazepam• baclofen• carbamazepine• tetrabenazine(with lithium)• triple therapy : tetrabenazine, fluphenazine, trihexyphenidyl• intrathecal baclofen infusion• thalamotomy
  • 72. Botulium toxin(I)• Clostridium botulium : produce immunologically distinct toxin(A-G)• cleaved into a heavy chain(100K) & light chain(50K) , linked by a disulfidebond, by trypsin or bacterial enzyme• BTX A & E : cleave SNAP-25(synaptosome associated protein), a protein forsynaptic vesicle targeting & fusion with presynaptic membrane• BTX B, D & F : cleave synaptobrevin-2(VAMP, vesicle associated membraneprotein)• BTX C : cleave syntaxin, plasma membrane associated proteinTotal maximum dose of Botox6 U/kg every 2 months
  • 73. Botulium toxin(II)Mechanism of action• blocks acetylcholine release by cleaving SNAP-25• not affect the synthesis or storage of acetylcholine or the conduction of electricalsignalsSide effect : transient, mild* in blepharospasm, ptosis, blurring of vision, tearing, local hematoma(< 2 wks)Contraindication• previous allergic reaction• motor neuron disease• myasthenia gravis or Eaton-Lambert syndrome• aminoglycoside use : increased effects of Botox therapy• Pregnancy• presence of infection at the proposed injection site
  • 74. Botulium toxin(III)Dilution of Botox• with 0.9% Sodium Chloride Injection, store in a refrigerator• 100 U/vial• added dilutent Resulting dose Units per 0.1 mL1.0 mL 10 U2.0 mL 5 U4.0 mL 2.5 U8.0 mL 1.25 UAntibody against Botox• 4.3 % - 10.5 %• For long term response* minimal effective dose* maximize treatment interval( at least 1 month)* minimize protein expose(less boosters)
  • 75. Key structures in the neck tokeep in mind for injection• Trachea7th cervical spinal nerveTrapeziusThyroid glandVertebral vesselsBrachial plexusSympathetic trunkExternal jugularInternal jugularCommon carotidSCM
  • 76. Botulium toxinBlepharospasm• moderate or marked improvement in 94 %• average improvement latency : 4.2 days,• average duration of maximum benefit : 12.4 wks• Injection :* orbicularis oculi, avoid inf. Med. Part(lacrimal duct) & central upperlid(levator palpebra)* pretarsal rather than preseptal portion of orbicularis oculi• 5 U in each site in the upper lid & 5 U in the lower lid laterally only* hemifacial spasm & older people : less
  • 77. Oromandibular dystonia• rarely improve with medication, no surgical treatment• average latency : 5.5 days, average duration : 11.5 wks• transient swallowing problem : 1/3• in jaw-closure dystonia : masseter muscle* in jaw-opening dystonia : submental muscle or lateral pterygoid muscleSpasmodic dysphonia• unilateral injection : superior & longer lasting benefit than bilateral(Adams,1993)• unilateral : 5 - 30 U• adverse effect : transient breathy hypophonia, hoarseness & rare dysphagia withaspiration• injection : posterior cricoarytenoid muscle, posterior to thyroid laminaWriter’s cramp• average latency : 5.6 days, average duration : 9.2 wks• Injection : belly of the most active muscle in EMG study* wrist flexor or extensor
  • 78. Cervical dystonia(I)• goal of therapy* improve abnormal posture & neck pain* prevent secondary complication(contracture, cervical radiculopathy, cervicalmyelopathy)• average improvement : 1 week, average duration : 3-4 months• adverse effect : dysphagia(14 %), neck weakness, nausea• Favorable response* proper selection of involved muscle* appropriate dosage* short-duration dystonia• Examination of the Pts with cervical dystonia* allow head to draw into the maximal abnormal posture without resisting* examine while standing, walking, sitting & writing* passively move the head* palpate contracting muscle* EMG
  • 79. Cervical dystonia(II)• Muscles involved in cervical dystoniaMuscle Flexion Rotation Tilt Extension Shoulderelevationlongus coli biSCM bi contra ipsiscalene bi ipsilevator ipsi ipsiscapulaetrapezius ipsi ipsi bi ipsisplenius ipsi ipsi bicapitispost. Paraspinalis ipsi bi
  • 80. Cervical dystonis(III)• Number of injected sites per muscle* SCM(2 sites), scapulae & trapezius(more sites)• Doses for each muscleMuscle Range of doses(units) Average dose(units)longus coli 20-50 25SCM 40-75 50scalene 40-60 50lavator scapulae 50-100 50trapezius 80-120 100splenius capitis 80-200 150post.paraspinalis 40-100 80(semispinalis capitis& longissimus capitis)
  • 81. • Dyskinesia• This is a symptom of an underlying movement disorder.Dyskinesia literally means abnormal (dys) movements (kinesia).• This is characterized by spasms, tics and twitches or morecomplex slow writhing movements (athetosis), rapid, jerkymovements (chorea) or spasm of a group of muscles (dystonia).• There may be hypokinesia or paucity of movement or akinesialack of movements and brady kinesia or slowing of movements.These are all commonly seen in Parkinson’s disease.• These complex abnormalities of movement may appear slowly ormay appear suddenly and unpredictably with a rapid return tonormal.• Dyskinesia may be seen in Parkinson’s disease and other similarconditions. They may be seen on intake of certain drugs like
  • 82. activity have been detected by positron-emission tomography (PET) and globuspallidus recordings. PET and fluoro-MRIimaging generally show increased restingglucose metabolism in premotor cortex andlentiform nucleus as well as possibly abnormalactivity in premotor and primary motor cortex.Electrophysiological studies indicate impairedCNS inhibitory activity. Impaired surroundinhibition may contribute to spread of neuralactivity to regions adjacent to activated neuralcircuits, potentially accounting forinappropriate overflow of movement intoadjacent muscles. Sensorimotor representationsof affected body parts in focal dystonia areenlarged in the cerebral cortex. However, itremains unclear if these changes are primary orsecondary.
  • 83. Management/Treatmentacute dystonic reactions - diphenhydramine or benzatropine Ongoinggeneralised dystonia - levodopa- physiotherapy- antispasmodic- treatment of underlying disease- trihexyphenidyl- physiotherapy- antispasmodic- treatment of underlying disease- deep brain stimulation (DBS)- physiotherapy focal dystonia: other than adult isolated foot - botulinumtoxin- physiotherapy- transcutaneous electrical nerve stimulation- treatment of underlying disease- speech therapy- deep brain stimulation (DBS)- physiotherapy adult isolated foot dystonia - levodopa- physiotherapy- treatment of underlying disease- trihexyphenidyl- physiotherapy- treatment of underlying disease- botulinum toxin- physiotherapy- treatment of underlying disease
  • 84. EpidemiologyEstimates from population studiesof the prevalence of early-onsetdystonia vary widely, ranging fromas low as 7 per 100,000 to as highas 500 per 100,000. A 1998epidemiological study inRochester, Minnesota, US led to anestimate of 88,000 people in the USwith primary focal dystonia,representing a prevalence of 33 per100,000, but this was probably anunderestimate due to undiagnosedcases
  • 85. identified structural lesion or toxinresponsible for the dystonia,although in some cases, a geneticmutation can be identified,particularly in some early-onset orfamilial cases. However, mostprimary dystonias remainidiopathic. A family history is notuniformly present in genetic formsof dystonia due to reducedpenetrance. Several genetic factorshave been identified in associationwith dystonia. These includeautosomal-dominant (often withincomplete penetrance), autosomal-recessive, X-linked, andmitochondrial genetic causes.Mutations in the DYT1 gene thatencode TorsinA can be found in
  • 86. Compare and contrast childhood-onset dystonia with adult-onsetprimary dystoniaChildhood-onset dystonia oftenbegins in the lower body andbecomes generalized. It iscommonly inherited. Adult-onsetdystonia often begins as a focaldystonia of the neck or face andcan become segmental ormutifocal, but rarely does itgeneralize. It is commonly sporadic
  • 87. Using transcranial sonography(TCS) as a noninvasive, easy toperform, and side-effect-freemethod, it could be shown that inup to 75% of patients with cervicaldystonia (CD), in a high percentageof other focal dystonias, but seldomin facial and genetically determineddystonia, hyperechogenicity of themedial part of the lentiform nuclei(LN) can be visualized in the thirdventricular scanning plane. Basedon these TCS findings an increasedcopper content of the LN could beverified in dystonia, opening newperspectives on possiblepathophysiological aspects andfuture research. In clinical routine,this method may be used for early
  • 88. 2- Secondary dystonia• CP, delayed-onset dystonia, encephalitis, CJD, SSPE,HIV infection• head trauma, primary antiphospholipid syndrome,AVM, hypoxis, stroke.• brain tumor, MS, CPM, spinal cord injury,psychogenic• Drug-induced : levodopa, ergotamine, AED,dopamine D2 Rc blocking agent(butyrophenone,phenothiazine, tetrobenazine)• toxin(Mn, CO, carbon disulfide, cyanide, disulfiram),hypoparathyroidism