The document discusses the definition, classification, features, and pathophysiology of dystonia. It is classified based on age of onset, distribution, and etiology. Primary dystonias have no known underlying brain lesion and can be hereditary or idiopathic in nature, while secondary dystonias have an identifiable cause such as drugs, toxins, or other neurological conditions. The pathophysiology of primary dystonias involves subtle changes in neuronal signaling and communication in basal ganglia circuits that lead to abnormal patterns of muscle contraction.

1. Update of
dystonia
DR/ AYMAN AL-MALT
ASSISTANT LECTURER NEUROLOGY

2. • Defintion of spectrum of movement disorder and
dystonia
• Classification of dystonia

4. Movement disorders
• Disturbance in speed or fluency of voluntary
movement
or
• the presence of unintended extra movement
• Extrapyramidal diseases
• Hyperkinetic excessive amount of spontanous motor
activity and abnormal involuntary move occur
• Hypokinetic Cx by akinesia or bradykinesia in which
purposeful motor activity is absent or reduced.

5. 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.

6. The spectrum
Ballismus DystoniaChorea Athetosis
Movements become - Less violent / explosive / jerky
- Smoother and more flowing
- More sustained
They differ from tics in that they cannot be suppressed by
voluntary control
Myoclonus
6

7. Basal ganglia
• Basal ganglia regulate the initiation , scaling
and control of the amplitude and direction of
movement
• Movement disorders arise from biochemical
or structural abnormalities in these
structures.

8. ..con
during an intended /projected movement one
set of activities is facilitated all the other are
surpassed.
• BRAKE prevents the target structures from
generating unwanted motor activity
• Switch selects which of the many available
will be activated at any given time

9. Definition of dystonia
• Oppenheim(1911) : “dystonia musculorum
deformans”, a syndrome in children with twisted
posture, muscle spasms, bizarre walking &
progression of symptom, leading to sustained fixed
postural deformity.
• Flatau & Sterling(1911) : inherited disease &
progressive torsion spasm
• Derek Denny-Brown(1964) : a fixed or relatively
fixed attitude.
• Fahn et al (1987) : a syndrome of sustained muscle
contractions, fequently causing twisting & repetitive
movements, or abnormal postures

10. Features of dystonic movements(I)
• Speed : from slow to rapid, more often the latter
* myoclonic dystonia : so fast, prolonged burst on
EMG
* myoclonus : short duration burst on EMG
• Aggravated by voluntary movement, stress,
emotional upset , fatigue
* Action dystonia : dystonic movement with
voluntary movement
* Task specific dystonia : writer’s cramp,
musician’s cramp, chewing, speaking.

11. Features of dystonic movements
• Relieved by relaxation, hypnosis & sleep
* diminished by tactile or proprioceptive “sensory
trick” (geste antagoniste).
- Torticollis: hand on the chin or side of face .
- Oro-lingual dystonia: Touching the lips or
placing an object in the mouth.
• paradoxical dystonia : for dystonia at rest to be
improved by active movement; chewing alleviates
blepharospasm.
• Spreading to contiguous body parts: the younger the
onset, the more likely.

12. Features of dystonic movements
• Pain : uncommon
* except cervical dystonia : 75 % of Pts of cervical
dystonia
• “Dystonic storms” : a crisis of sudden marked
increase in severity
• Lead to rhabdomyolysis & myoglobinuria:
admission to ICU

13. Features of dystonic movements
• Ipsilateral overflow dystonia (IOFD):involuntry
movement of muscles adjacent to those involved in
dystonia.
• Contralateral OFD: dystonic movement in normal
contralateral limb during dystonic movement or
posture of limb 1ry involved by dystonia
• Mirror dystonia: dystonic movement induced by
specific task like writing done by opposite homologus
normal body part.

14. Classification of dystonia
• Age at onset
• Distribution
• Etiology

15. Classification by age at onset
Age most important single factor a/w prognosis of primary
dystonia. the younger age at onset, the more severe & the more
spread of dystonia.
Childhood-onset (0-12 yrs)
• most often hereditary : probably autosomal dominant with
incomplete penetrance.
• progress to generalized type.
Adolescent-onset (13-20 yrs).
Adult-onset(> 20 yrs).
• most often sporadic, remain focal type(no progress to
generalized type)

16. 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 involvement
of any other area of the body

17. Classification by distribution
Multifocal dystonia
• two or more noncontiguous parts of the body
Hemidystonia
• affect one-half of the body
• symptomatic rather than primary

18. Classification by Etiology(I)
1- Primary dystonia
(ITD, dystonia musculorum deformans)
• no known underlying brain lesion
• hereditary & idiopathic form
• the only neurologic abnormalities : dystonia
2- secondary dystonia

19. 1- Primary dystonia
Childhood and adolescent onset
• DYT1: AD with reduced penetrance (~30%), early
limb onset with predominant family phenotype•
Adult onset
• DYT7: AD, cervical onset in adults.
Mixed phenotype
• DYT6, DYT 13: AD, early and late onset with possible
cranial, cervical, and sometimes limb onset and
variable spread
 Other genes to be identified

20. Idiopathic torsion dystonia DTY1
• Dystonia without any other abnormal involuntary
movement
• 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 the
Torsin A gene.
• Late-onset DTY6, cervical cranial-cervical onset :
genetic heterogeneity.
• DYT1 Variable phenotype - may present only with
writer's cramp.

21. Early-onset Late-onset
< 15 yrs > 20 yrs
frequently onset in leg focal onset(cranial)
commonly generalized remain focal
usually hereditary usually sporadic
DTY1 DYT7
Responds well to globus pallidus stimulation.
DYT6 : Later onset than DYT1, with dysphonia.
Check for this if DYT1 is negative, or cranio-cervical
onset.

22. Ashkenazi Non-Jewish
Mode of
inheritance
100 % AD 85% AD
Penetrance 30 40
9q haplotype Yes No
GAG TOR1A
deletion
90 40-65
Age of onset
>40
rare 10-15
incidence 1/6000-1/2000 1/160,000
% new mutation Rare 14
DYT1 Features in Ashkenazi and
Non-Jewish Populations

23. Idiopathic torsion dystonia(II)
• Onset : in 4th to 6th decades
• foci in the axial skeletal muscles(cranium and neck), rarely
generalized
• 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 (trapezius
and sternocleidomastoid)
 Spasmodic dysphonia: strained or breathy speech
 Oromandibular dystonia: involuntary jaw opening/closing
and tongue movement
 "Writers Cramp": a dystonia affecting the hand and arm
muscles, usually occurring with intended movement
(adult type)

24. Blepharospasm
Bilat, synchronous the involuntary
contraction of the eyelids, leading to
uncontrollable blinking and closure of the
eyelids.
 women> men 6th
decade, functional blindness
Aggravated by watching TV, readig
Relieved by touching eyelid
Spasm remain focal or spread to OM area
Meige syndrome, Bruegel disease

25. Blepharospasm
• the first symptom to appear is an increased rate of
blinking .
• uncontrollable squinting/closing of eyes
• light sensitivity(photophobic)
• squinting/eyes closing during speech
• uncontrollable eyes closing shut (rare instances
completely causing blindness)
• In addition, in some patients, the dystonic spasms may
sometimes be provoked by certain activities, such as
talking, chewing,

26. The term "facial tic" is often used to describe
involuntary movements that involve the face,
particularly those around the eyes and the corner of the
mouth. These movements are usually brief and not
sustained. They are usually not associated with the
"squeezing" of the muscles around the eyes that
typically accompanies blepharospasm
What is the difference between facial tic
and blepharospasm

27. Brueghel's syndrome
• Blepharospasm-oromandibular dystonia
syndrome: open mouth
• A variant of adult-onset torsion dystonia?
When OMD is combined with blepharospasm, The
symptoms usually begin between the ages of 30 and 70
years old and appear to be more common in women
than in men (2:1 ratio)
The incidence is about one case in 20,000 people
Meige syndrome

28. MEIGESYNDROME.flv

29. 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

30. Spasmodic dysphonia
• Dystonic spasm in laryngeal muscles
• 4th
to 5th
decades
• Adductor types :most common,strained ,high
pitched associated with repetitive brief interruption
of speech,singing and whispering reduce spasm
• Abduction type :whispering breathy
• mixed

31. 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 abnormal
head movements occur because of contractions of the
sternocleidomastoid, trapezius, and posterior cervical
muscles. This effect results in a patterned, repetitive,
and spasmodic movement that causes the head to
twist (rotational torticollis), extend (retrocollis), flex
(anterocollis), or tilt toward the shoulder
(laterocollis).

32. Cervical dystonia
Complications of cervical dystonia
Pain experienced by 93% of
patients
Difficulty reading, driving,
watching TV
Withdrawal from social
interactions
Spontaneous remission 10-20%
not sustained
Cervical Dystonia Patient Traits:
Prevalence: 9/100,000
Mean age of onset: 41 to 42 yrs Female: 62% to 67%
Abnormal postures: 83%
Head jerks/neck spasms: 62% Pain: 90%
Types of postures in
cervical dystonia
Torticollis: 82-97%
Laterocollis: 42-63%
Retrocollis: 29-32%
Anterocollis: 14-25%
Most patients show
combination

33. Neck and shoulder mm affected in cervical dystonia
Splenius capitis
Levator scapulae, Trapezius
Sternocleidomastoid, Scalenes
Longissimus, Splenius cervicis

34. Torticollis mm involvement
Primary: Ipsi splenius, contra
SCM
Secondary: Ipsi semispinalis,
ipsi longissimus, splenius
cervicis,
levator scapulae, interior
oblique, longus capitis
Laterocollis mm
Primary: Splenius capitis,
ipsi scalenes,
levator scapulae,
longissimus
Secondary: Splenius cervicis
Retrocollis mm
Primary: Bilateral
splenius capitis,
posterior vertebrals
Secondary: Splenius
cervicis
Anterocollis mm
involvement
Primary: Bilateral
SCM
Secondary: Scalene
complex

37. Limb dystonia
Writer’s cramp:
- Dystonic posturing of arm when hand used to perform
specific tasks e.g. writing, playing piano
Paiful
Equal both sexes

39. Pathophysiology of 1ry dystonias
• No clear neurodegenerative processes.
• Abnormalities are likely subtle changes in
neuronal signaling and communication.
• BG implicated, with some evidence of reduced
output from the GPi, although this is
contradicted by symptom improvement
following GPi lesioning.
• Also evidence of cortical dysfunction and
abnormal sensory afferent processing.

40. Pathophysiology of 1ry dystonias
• Alteration in the pattern of pallidal-thalamic activities
during voluntary movement and abnormal sensory
feedback lead to an increase in abnormally
synchronous cortical output and thus co-contraction of
multiple muscle groups or overactivation of intended
muscle groups.
• In addition, abnormal thalamic activity synchronizes
the intended movement as well as unwanted overflow
movements in other muscles

41. Pathophysiology
 Generalised dystonia is a disorder of the CNS, the
pathophysiology of acquired torticollis remains
poorly understood.
The observable end result is a centrally activated
(but involuntary), sustained contraction of skeletal
muscle, resulting in abnormal posture.
Neurophysiological and functional imaging studies
have implicated abnormalities in the BG, as well as
sensory and motor cortices.
There is also evidence of abnormalities in dopamine
signalling, sensory processing, cortical motor
inhibition, and sensorimotor integration.

42. Quantitative voxel-based morphometry studies
have shown decreased volumes of caudate,
putamen, and sensorimotor cotex compared to
control subjects.
pathogenesis of dystonia
still unclear, hypothesis: alteration in pattern of
the pallidal-thalamic activities during
voluntary movement + abnormal sensory
feedback leads to abnormally synchronous
cortical output

43. 2- Secondary dystonia
• Variety of lesions, mostly involving the BG and/or
dopamine synthesis.
1. Inherited nondegenerative (dystonia plus)
• Dopa-responsive dystonia: due to DYT5 and other
genetic defects
• Myoclonus dystonia: due to DYT11 and possibly
other genetic defects
• Rapid-onset dystonia parkinsonism: due to DYT12

44. 2- Secondary dystonia
2. Inherited degenerative
• • Autosomal dominant, autosomal recessive,
X-linked (DYT3), mitochondrial
3. Degenerative disorders of unknown etiology
• Parkinson disease
• Progressive supranuclear palsy
• Corticobasal ganglionic degeneration

45. 2- Secondary dystonia
4. Acquired
• • Drugs (dopamine-receptor blockers), other
• Toxins • Head trauma
• • Stroke, hypoxia
• • Tumors • Peripheral injuries
• • Encephalitis, infectious and postinfectious
5. Other movement disorders with dystonic
• Tics, paroxysmal dyskinesias (DYT8, DYT9,DYT10)
6. Psychogenic Dystonia

46. Classification by etiology(II)
Dystonia-plus syndrome
• dystonia a/w parkinsonism or myoclonus without known
neurodegeneration
• DRD & myoclonic dystonia(neurochemical disorder)
Heredodegenerative disease
• X-linked recessive
* Lubag : DYT3 gene(Xq 13), filipino male, young adult onset, cranial
dystonia, 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

47. 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 for
GTP(guanosine triphosphate cyclohydrolase I
: rate limiting enzyme in formation of
tetrahydrobioptern, cofactor of tyrosine hydroxylase
& phenylalanine hydroxylase
• focal dystonia, typically dystonia of lower limbs
affecting gait progress to G

48. FIGURE 2.2 Diagram of GCH1
defect pathway.

49. Dopa-responsive dystonia
• paraparesis
• diurnal variation : no symptom in morning, worse
at night, worsen after exertion
• parkinsonian features
• markedly improve with low dose levodopa(100-300)
per day divided dose.
* no adverse effects of response fluctuation despite
long use
• Often misdiagnosed as cerebral palsy.
• Phenylalnine loading test

50. Phenylalnine loading test
• Phenylalnine loading test: ingestion PA
(100mg/kg) sampling 1ml plasma 0, 1, 2, 4,
& 6 hours later Phenylalanine levels peak
at 2 hrs and are markedly elevated at 4 and 6
hrs compared to controls. Tyrosine levels do
not increase at all increased Plasma
Phe/Tyr profile

51. Juvenile PD DRD Childhood PTD
onset age rare < 8 infancy to 12 uncommon < 6
gender male predom. Female predom. Equal
initial Sx foot dystonia/PD leg dystonia arm or leg
gait disorder
diurnal no sometimes no
bradykinesia present present no
Anti-Ch yes yes yes
response
Dopa R yes yes no or mild
Dopa mod to high very low high
dosage
“off” fluctuation uncommon unknown
dyskinesia prominent uncommon unknown
FluoroDopa decreased normal normal
PET
βCIT SPECT decreased decreased normal
Phe load test normal abnormal normal
Prognosis progressive plateaus usually worsen

52. Rapid-onset dystonia - parkinsonism
(RDP)
• Autosomal dominant inheritance ch 19q13
• adolescent & adult onset
• Clinical features( severe worsening, bulbar)
* sudden onset of dysarthria, dysphagia, severe
dystonic spasm, bradykinesia & postural instability
over 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 HVA
concentration
• No effective ttt
Synonym: DYT12

53. Myoclonic dystonia DYT11
• MD is a distinct genetic disorder in which dystonia,
usually mild and not always present, is associated
with 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

54. Myoclonus dystonia. DYT11
• dystonia - typically cervical / writer's cramp.
• The myoclonic jerks can be triggered by voluntary
movements (action myoclonus). Manifested as
overflow jerks (i.e., involving body regions not
involved in the action perse).
• The myoclonic component may respond to alcohol.
• psychiatric complications, particularly OCD,
anxiety, alcohol abuse
• Clonazepam, valporic acid.

55. 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

56. Paroxysmal Dyskinesias
• PDs are rare neurological disorders, characterized by
a sudden onset of dystonic, choreatic, athetotic, and
ballistic movements with variable underlying
mechanisms.
• The inherited paroxysmal dyskinesias, associated
with gene loci DYT8 and DYT10, differ from the
above- described genetic dystonias insofar as the
dystonic features are clinically transient.
• The pathogenesic mechanisms that underlie these
fluctuating disorders await further clarification,.

57. Paroxysmal nonkinesigenic
dystonia/dyskinesia (PNKD)
• PNKD is an AD. As its name implies, it is
characterized by paroxysms of hyperkinesias, which
can include dystonia, dyskinesia, choreoathetosis,
and ballism.
• The paroxysms are not triggered by volitional
movements, but may be precipitated by various
factors such as stress and alcohol.
• Age of onset varies from infancy to adulthood, with
adolescence being most common.
• several times a day and last from minutes to hours.
Scott Spasms March 28 2010.flv

58. Paroxysmal kinesigenic
dystonia/dyskinesia (PKD)
• PKD is also AD, though sporadic cases have been
reported. There is likely significant variable
expressivity, with an apparent male predominance.
• Tomita and colleagues studied several affected
Japanese families in 1999 and mapped the disease
locus to chromosome 16. Different loci on
chromosome 16 may be responsible in other affected
families.
• Age of onset :childhood. Seizures infancy.
• triggered by sudden movement, are usually short—
lasting less than a few minutes, and can occur

59. Age of onset is in the first or second decade of life
childhood or late adulthood has been reported
[Demirikiran and Jankovic, 1995; Fahn, 1994].
Males are more commonly affected than females with a
ratio of 3.75 : 1 [Fahn, 1994].
Mostly, PKDs are idiopathic, and in the majority, there
is a family history of AD inheritance with penetrance >
70%.
Sporadic cases are reported frequently [Jankovic and
Demirkiran, 2002].
Some cases of PKD may be symptomatic secondary to
multiple sclerosis (MS), brain trauma or endocrine
dysfunction [Bhatia, 1999].
PKD Paroxysmal kinesigenic dyskinesia-PKD A New Treatment.flv

60. Features of PNKD & PKD
PNKD PKD
Chromosome 2 16
Mode of inheritance AD AD
Age of onset Adolescence Childhood
Triggers Coffee, alcohol,
fatigue
Movements
Frequency of
attacks
DAILY Hundreds/day
Associated features Infantile seizures
Response to AEDs Carbamazepine

61. Psychogenic dystonia
Clues relating to the movements
• abrup onset, inconsistent movement.
• incongruous movement(not fit with recognized
pattern or normal physiological pattern)
• presence of additional types rhythmic shaking,
bizarre gait, excessive startle, deliberate slowness
carrying out requested voluntary movement
• spantaneous remission
• disappear with distraction, response to placebo.
• dystonia beginning as a fixed posture
• presence as a paroxysmal disorder.

62. Psychogenic dystonia
Clues 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 insurance
claims
• presence of secondary gain
• litigation or compensation pending

63. Tardive dyskinesia tardive dystonia
• meaning they have a slow or late onset
• This is a common complication of long-term
antipsychotic drug treatment due to dopamine
receptor antagonism. The precise mechanism is
unknown, but the risk appears to increase with
advancing age or in children and infants as a side
effect from usage of drugs for gastrointestinal
disorders.
• When medication is withdrawn relatively early in a
patient's treatment, the dyskinesia may reverse,
whereas after 6 months of exposure, the movement
disorder may persist indefinitely.

64. Tardive dystonia
• The clinical features of tardive dyskinesia
include abnormal choreoathetoid movements,
especially involving, in adults, the face and
mouth (ie, blepharospasm, torticollis,
oromandibular dystonia), and in children, the
limbs
• Risk factors: old age, >6 months therapy,
depot injection, genetically preclinical
parkinson

65. Dystonia (cont.)
• Primary Dystonia
– may be due to DYT1 mutation
• Secondary Dystonia
– Most common cause is neuroleptic
administration
– Dystonia assoc. with parkinsonism
– Psychogenic causes

66. Dystonia (cont.)
• Diagnostic Challenge: Frequent Misdiagnoses
– Blepharospasm
• Dry eye syndrome or tics
– Cervical dystonia
• Stiff neck, arthritis, subluxation of the cervical
vertebrae, posterior fossa tumors
– Writer’s cramp
• Carpal tunnel, strain, “tennis elbow”

67. Dystonia (cont.)
• Frequent Misdiagnoses (cont.)
– Laryngeal dystonia
• Sore throat, laryngitis, vocal abuse
– Oromandibular dystonia
• TMD (temporomandibular joint disorder)
– All dystonia
• Psychogenic, stress, nervousness

68. • Investigations to consider in dystonia
• FBC (inc acanthocytes), plasma
caeruloplasmin, 24 hour urinary copper
excretion and slit lamp examination, genetic
testing (DYT1 in young onset), MRI brain
scan, therapeutic trial of L-dopa.

69. • Prognosis of dystonia
• no way to predict symptoms fluctuate
-stabilization is usually seen in 5 years

70. Management/Treatment
without pain or functional
impairment - observation
with functional impairment or pain
or diminished quality of life - oral
medications
- physiotherapy
- intramuscular botulinum toxin
- physiotherapy Ongoing refractory
to therapy with botulinum toxin -
deep brain stimulation
- physiotherapy
- radiofrequency ablation
- physiotherapy
- injected phenol
- physiotherapy
- baclofen injection via continuous
pump infusion

71. Treatment of dystonia(I)
Physical & supportive therapy
• physical therapy & brace : improve posture & prevent contracture
a substitute for a “sensory trick”
• muscle relaxation technique & sensory feedback therapy : adjunct
Dopaminergic therapy
• in DRD, small dose of levodopa(100mgof levodopa with 25mg of
decarboxylase inhibitor)
* also improve with anticholinergic & carbamazepine
• in Pts with idiopathic or other types of dystonia : rarely improved with
dopaminergic therapy
Antidopaminergic therapy
• usually limited(Jankovic, 1995)
• Tardive dystonia : tetrabenazine, Risperidone(D2 dopamine Rc blocking
with high affinity for 5HT2 Rc), Clozapine(D4 Rc blocking , relatively
low affinity for D2 Rc, high affinity for 5-HT2A Rc)

72. 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 weeks
switch to SR preparation
* S/E : dose-related drowsiness, confusion, memory difficulty, hallucination
Other pharmacologic therapy
• Benzodiazepine(clonazepam or lorazepam) : additional effect in case of
unsatisfactory anticholinergic response
* clonazepam : useful for blepharospasm & with myoclonic dystonia
• Baclofen : helpful for oromandibular dystonia
* intrathecal baclofen : more effective in dystonia with spasticity or pain

73. Treatment of dystonia(III)
• Peripheral deafferentiation : somatosensory input in the pathogenesis of
dystonia
* 5-10 ml of 0.5 % lidocaine
• Kinesigenic paroxysmal dystonia : AED(carbamazepine, phenytoin)
• non-kinesigenic paroxysmal dystonia : clonazepam, acetazolamide

74. Treatment of dystonia(IV)
Blepharospasm
• clonazepam, lorazepam
• Botox
• trihexyphenidyl
• orbicularis oculi myectomy
Oromandibular dystonia
• baclofen
• trihexyphenidyl
• Botox
Spasmodic dysphonia
• Botox
Cervical
• trihexyphenidyl
• diazepam, lorazepam, clonazepam
• Botox
• tetrabenazine
• carbamazepine
• baclofen
Task-specific dystonia(writer’s cramp)
• benztropine, trihexyphenidyl
• Botox
• occupational therapy

75. 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

76. Botulium toxin(I)
• Clostridium botulium : produce immunologically distinct toxin(A-G)
• cleaved into a heavy chain(100K) & light chain(50K) , linked by a disulfide
bond, by trypsin or bacterial enzyme
• BTX A & E : cleave SNAP-25(synaptosome associated protein), a protein for
synaptic vesicle targeting & fusion with presynaptic membrane
• BTX B, D & F : cleave synaptobrevin-2(VAMP, vesicle associated membrane
protein)
• BTX C : cleave syntaxin, plasma membrane associated protein
Total maximum dose of Botox
6 U/kg every 2 months

77. 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 electrical
signals
Side 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

78. 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 mL
1.0 mL 10 U
2.0 mL 5 U
4.0 mL 2.5 U
8.0 mL 1.25 U
Antibody 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)

79. Key structures in the neck to
keep in mind for injection
• Trachea
7th cervical spinal nerve
Trapezius
Thyroid gland
Vertebral vessels
Brachial plexus
Sympathetic trunk
External jugular
Internal jugular
Common carotid
SCM

80. Botulium toxin
Blepharospasm
• 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 upper
lid(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

81. 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 muscle
Spasmodic dysphonia
• unilateral injection : superior & longer lasting benefit than bilateral(Adams,
1993)
• unilateral : 5 - 30 U
• adverse effect : transient breathy hypophonia, hoarseness & rare dysphagia with
aspiration
• injection : posterior cricoarytenoid muscle, posterior to thyroid lamina
Writer’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

82. Cervical dystonia(I)
• goal of therapy
* improve abnormal posture & neck pain
* prevent secondary complication(contracture, cervical radiculopathy, cervical
myelopathy)
• 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

83. Cervical dystonia(II)
• Muscles involved in cervical dystonia
Muscle Flexion Rotation Tilt Extension Shoulder
elevation
longus coli bi
SCM bi contra ipsi
scalene bi ipsi
levator ipsi ipsi
scapulae
trapezius ipsi ipsi bi ipsi
splenius ipsi ipsi bi
capitis
post. Paraspinalis ipsi bi

84. Cervical dystonis(III)
• Number of injected sites per muscle
* SCM(2 sites), scapulae & trapezius(more sites)
• Doses for each muscle
Muscle Range of doses(units) Average dose(units)
longus coli 20-50 25
SCM 40-75 50
scalene 40-60 50
lavator scapulae 50-100 50
trapezius 80-120 100
splenius capitis 80-200 150
post.paraspinalis 40-100 80
(semispinalis capitis
& longissimus capitis)

85. • 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 more
complex slow writhing movements (athetosis), rapid, jerky
movements (chorea) or spasm of a group of muscles (dystonia).
• There may be hypokinesia or paucity of movement or akinesia
lack 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 or
may appear suddenly and unpredictably with a rapid return to
normal.
• Dyskinesia may be seen in Parkinson’s disease and other similar
conditions. They may be seen on intake of certain drugs like

86. activity have been detected by positron-
emission tomography (PET) and globus
pallidus recordings. PET and fluoro-MRI
imaging generally show increased resting
glucose metabolism in premotor cortex and
lentiform nucleus as well as possibly abnormal
activity in premotor and primary motor cortex.
Electrophysiological studies indicate impaired
CNS inhibitory activity. Impaired surround
inhibition may contribute to spread of neural
activity to regions adjacent to activated neural
circuits, potentially accounting for
inappropriate overflow of movement into
adjacent muscles. Sensorimotor representations
of affected body parts in focal dystonia are
enlarged in the cerebral cortex. However, it
remains unclear if these changes are primary or
secondary.

87. Management/Treatment
acute dystonic reactions - diphenhydramine or benzatropine Ongoing
generalised 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 - botulinum
toxin
- 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

88. Epidemiology
Estimates from population studies
of the prevalence of early-onset
dystonia vary widely, ranging from
as low as 7 per 100,000 to as high
as 500 per 100,000. A 1998
epidemiological study in
Rochester, Minnesota, US led to an
estimate of 88,000 people in the US
with primary focal dystonia,
representing a prevalence of 33 per
100,000, but this was probably an
underestimate due to undiagnosed
cases

89. identified structural lesion or toxin
responsible for the dystonia,
although in some cases, a genetic
mutation can be identified,
particularly in some early-onset or
familial cases. However, most
primary dystonias remain
idiopathic. A family history is not
uniformly present in genetic forms
of dystonia due to reduced
penetrance. Several genetic factors
have been identified in association
with dystonia. These include
autosomal-dominant (often with
incomplete penetrance), autosomal-
recessive, X-linked, and
mitochondrial genetic causes.
Mutations in the DYT1 gene that
encode TorsinA can be found in

90. Compare and contrast childhood-
onset dystonia with adult-onset
primary dystonia
Childhood-onset dystonia often
begins in the lower body and
becomes generalized. It is
commonly inherited. Adult-onset
dystonia often begins as a focal
dystonia of the neck or face and
can become segmental or
mutifocal, but rarely does it
generalize. It is commonly sporadic

91. Using transcranial sonography
(TCS) as a noninvasive, easy to
perform, and side-effect-free
method, it could be shown that in
up to 75% of patients with cervical
dystonia (CD), in a high percentage
of other focal dystonias, but seldom
in facial and genetically determined
dystonia, hyperechogenicity of the
medial part of the lentiform nuclei
(LN) can be visualized in the third
ventricular scanning plane. Based
on these TCS findings an increased
copper content of the LN could be
verified in dystonia, opening new
perspectives on possible
pathophysiological aspects and
future research. In clinical routine,
this method may be used for early

92. 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