1. AN OVERVIEW OF DYSTONIA: practical approach and therapeutics
By: Dr. Hesham Abboud
Assistant lecturer of Neurology
Faculty of Medicine, University of Alexandria
Clinical fellow of movement disorders, Neurological institute,
Cleveland Clinic

2. Definition
Dystonia is a movement disorder characterized by involuntary sustained muscle contractions often of antagonistic muscle groups resulting in repetitive twisting movements and\or abnormal postures.
Historical background:
In 1908 Schwalbe described dystonia for the first time in 3 siblings from an Ashkenazi Jewish family in Eastern Europe. He used the term “chronic cramps” and regarded the condition as hysterical.
In 1911 Oppenheim used the term dystonia for the first time and recognized the disorder as organic in nature. For years after that the term Oppenheim’s dystonia was used to describe early onset primary dystonia. More recently the term DYT1 replaced the old term.

4. Pathophysiology of dystonia
The exact pathophysiology of dystonia is unknown. Unlike other movement disorders the neurochemical dysfunction cannot be attributed to a particular neurotransmitter.
What we know:
Pathology: no neurodegeneration in primary dystonia and the abnormality is strictly functional.
Anatomical localization: globus pallidus, motor cortex, SENSORY cortex, cerebellum.
Neurochemical: based on medication response, some forms of dystonia result from dopaminergic and\or cholinergic dysfunction.

5. Pathophysiology of dystonia
Proposed pathogenesis:
Data from functional neuroimaging and electrophysiology suggest one or a combination of the following mechanisms:
decrease in the central inhibitory mechanisms.
Increase in neuroplasticity.
Impairment in sensory function.
The sensory theory of dystonia explains the “sensory trick” phenomenon, a unique feature of most focal dystonias. The sensory theory is becoming more popular nowadays and a lot of research is going on in this field.

6. Classification of dystonia
There are three major ways of classifying dystonia:
According to anatomical distribution: generalized, focal, segmental, multifocal, and hemidystonia.
According to etiology: primary or secondary.
According to age of onset: early onset (before 26 years) and late onset (after 26 years).

7. Classification of dystonia anatomical distribution
Focal: involving one body part e.g: hand (writer’s cramps), foot (runner’s dystonia), neck (cervical dystonia), ey lids (blepharospasm), ….etc. Focal dystonia can be task specific, task selective, or unrelated to task.
Segmental: involving two contiguous body parts: Meig syndrome (blepharospasm + oroamandibular dystonia).
Multifocal: involving two or more noncontiguous body parts (e.g. spasmodic dysphonia and writer’s cramps, very rare).
Generalized: involving the whole body. At minimum the trunk, one lower extremity and another body part. E.g DYT1, DYT5.
Hemidystonia: involving one side of the body. Almost always secondary to a structural lesion in the brain or the spinal cord.

8. Classification of dystonia: primary vs secondary
Primary dystonia refers to cases where:
dystonia is the ONLY neurological dysfunction resulting from an IDIOPATHIC or a GENETIC condition.
E.g. DYT1, cervical dystonia, writer’s cramps.
Secondary dystonia refers to cases where:
Dystonia is associated with other neurological dysfunction e.g. parkinsonism, myoclonus, dementia.
OR there is a known etiological cause: Wilson’s, drug-related, perinatal injury, CNS tumor, … etc.

9. Classification of dystonia secondary dystonia
Secondary dystonia can happen at any age and refer to conditions where there is a clear etiology and\or association with other neurological dysfunction.
It can be classified under four major categories:
Acquired causes.
Dystonia plus: dystonia coexist with another major neurological dysfunction.
Heredodegenerative conditions: dystonia is part of a generalized neuro or systemic degenerative condition.
Part of a Parkinsonian syndrome.

10. Secondary dystonia Acquired causes:
Perinatal cerebral injury: dystonic CP.
Drug-related: dopamine blockers\agonists.
Traumatic: brain or PERIPHERAL injury.
Structural lesions of the BG, brainstem, or spinal cord: tumor, granuloma, infarct, etc.
Rarely: paraneoplastic, infectious, collagenic, etc.
Dystonia plus:
DYT5 (DRD): AR\AD frequently associated with Parkinson-like features.
DYT3: X-linked dystonia-parkinsonism
DYT12 Rapid onset dystonia-parkinsonism. (RDP): AD.
DYT11,15 Myoclonus-dystonia syndrome: AD

11. Secondary dystonia Heredegenerative syndromes:
AD: HD, SCA (esp. SCA3), DRPLA.
AR: Wilson’s, neuroacanthosis, inborn errors of metabolism, PKAND, ataxia-telangectasia.
X-linked: Lesch-Nyhan.
Mitochondrial: Leigh’s.
Parkinsonian syndromes:
PD: can present with focal dystonia of the FOOT or one arm.
PSP: dystonia is very common especially cranial.
MSA: same as PSP.
CBD: unilateral dystonia of the alien limb.

12. Classification of dystonia: age of onset
Classification of dystonia according to age of onset with etiological and anatomical sub-classifications is the most clinically useful tool.
Early onset primary dystonia is almost always generalized but may start as focal dystonia and progress over time. Persistently focal dystonia in children is often secondary and should be worked up accordingly.
Late onset primary dystonia is almost always focal. Late onset generalized dystonia is extremely rare.
Remember: early – primary – generalized. Remember: late – primary - focal

13. Clinically useful classification
Early onset (<26):
Primary:
Generalized: DYT1.
Focal: very rare. some cases of DYT6 may present in teenage.
Secondary:
Generalized: DYT5, dystonic CP, Wilson’s, heredodegenerative.
Focal: structural lesion.
Late onset: (>26):
Primary:
Generalized: very rare cases of DYT1.
Focal: sporadic, DYT6, DYT7: torticollis, blepharospasm, s. dysphonia, writer’s cramps, .etc.
Secondary:
Generalized: wilson’s, heredodegenerative.
Focal: structural lesions, parkinsonian syndrome.

14. Classification of dystonia: genetic dystonias
Genetic dystonias are a group of disorders where dystonia is the main clinical feature and the mode of inheritance is Mandelian; I.e: AD, AR, or X-linked. They are referred to as DYT dystonias. About 16 subtypes have been recognized so far some of which are primary (dystonia only) or secondary (dystonia + other neurological dysfunction). Some present early and some present late.
Experts believe that all primary dystonia and dystonia plus syndromes have a genetic basis and research is ongoing to find out the abnormal genes for each of these conditions.
Genetic dystonia must be differentiated from Mandelian conditions where dystonia is NOT the main clinical feature (e.g Wilson’s disease).

15. Genetic dystonia

16. Common forms of dystonia

17. Early onset generalized dystonia DYT1
Early onset primary generalized dystonia.
AD with low penetrance (30%). GAG deletion in torsin A gene on Ch 9.
More common in Ashkenazi Jews.
Age of onset is around 9 yo. Starts with action dystonia of the foot or less commonly the hand. Spreads over a 5-year-period to become generalized. Most patients end up non ambulatory.
Normal perinatal course and patients remain with normal mentality.

18. Early onset generalized dystonia DYT1
Diagnosis: DYT1 gene detection is available. If this is not feasible, the D can be made clinically after ruling out DRD by levodopa therapeutic test. Wilson’s should be ruled out as well.
Treatment:
Medications may help early in the course: baclofen, benzos, anticholinergics.
DBS of the GPI is the mainstay of treatment.
Botox: not practical in generalized conditions. Can be used sparingly for specially problematic muscles.

19. Generalized dystonia

20. Dopa-responsive dystonia (DRD) DYT5
Early onset secondary generalized dystonia.
AD with low penetrance. Mutation in GCH1 gene resulting in dopamine deficiency. Segawa syndrome is an AR form of DRD with mutation in the tyrosine hydroxylase gene.
More common in females. Presents in the first decade of life with action dystonia of the foot that later spreads to other body parts and eventually generalize. Distinctive diurnal variation. Features of parkinsonism develop later in the course.
DD juvenile PD.

21. Dopa-responsive dystonia (DRD) DYT5
Evaluation: levodopa test: dramatic sustained (no wearing off) uncomplicated (no dyskinesia) response.
Treatment:
medications: levodopa (some patients go into prolonged remission and stop requiring levodopa).
Botox: no role.
DBS: no role.
NB: dopamine agonist responsive dystonia is a similar condition resulting from aromatic acid decarboxylase deficiency (AR). Responds to DA only e.g pramipixole.

22. Cervical dystonia Late onset primary focal dystonia.
Most cases are sporadic but some are positive for DYT6\7.
The most common primary focal dystonia.
More common in females.
C\P: - abnormal head\neck\shoulder position.
head tremor (often NO-NO tremor).
Pain in 50% of cases.
Prominent sensory trick.

23. Cervical dystonia

24. Cervical dystonia
Evaluation: clinical D. no need for further testing. DD of ET when presenting with head tremor.
Treatment:
Botox is the mainstay of treatment. Most commonly injected muscles for torticollis is the contralateral STCM and ipsilateral splenius capitis.
Medications: limited role. Only if botox not available.
DBS has been tried in few resistant cases with unimpressive results.
Surgery: muscle splitting or denervation. Discouraging results.

25. Cervical dystonia

26. Cervical dystonia

27. Blepharospasm
Late onset primary focal dystonia of the orbicularis occuli and surrounding muscles leading to forceful closure of the eyes.
Most cases are sporadic.
C\P: usually starts with a sense of eye irritation followed by photophobia leading to frequent blinking. This progresses into forceful spasmodic closure of the eyes in bright light and under mild stress (e.g. driving). May end in sustained eye closure and legal blindness. Some patients have a sensory trick.
Some cases have associated OMD (Meige’s syndrome).
Can be part of a parkinson plus syndrome (secondary).

28. Blepharospsm

29. Blepharospasm D is clinical. Look for signs of PSP, MSA. Treatment:
Botox is the mainstay of treatment. Injecting the palpebral part of the OO muscle is most effective.
Medications: limited role.
DBS: no role.

30. Oromandibular dystonia
Late onset primary focal dystonia.
Sporadic or genetic.
Some cases are unrelated to tasks and some are task specific.
High association with blepharospasm (Meige’s).
Types:
Jaw: jaw opening, jaw closure, jaw deviation, Jaw tremor.
Tongue: protrusion, deviation.
Lip: abnormal posturing.
Task specific: any of the above types occurring only with certain tasks e.g: embouchure dystonia in musicians.
Speech and eating are affected early in regular OMD and late in task-specific dystonia (after symptom spread).

31. Oromandibular dystonia
Evaluation: clinical D. rule out Wilson’s.
Treatment:
Botox is the mainstay Rx. Injection of masseter & temporalis for jaw closure and ptyregoids for jaw opening.
Retraining for task specific cases.
Medications: helpful if botox unavailable.
DBS: no role.

32. Spasmodic dysphonia
Late onset primary focal dystonia of the laryngeal muscles.
Most cases are sporadic. Abductor SD may be genetic (DYT4). High risk jobs include singers and teachers.
C\P: strained voice with breaks (adductor SD) or whispery voice (abductor SD). Rarely patients can present with a mixed type. Can be part of segmental or multifocal dystonia. Sometimes part of secondary dystonia e.g. PSP.
Adductor SD should be differentiated from voice tremor (part or variant of ET) although treatment is the same. SD «» ET.

33. Spasmodic dysphonia Evaluation: video stroboscopy. Treatment:
Botox is the mainstay of treatment. Injection of the thyroarytenoids in adductor SD (good results) and the post cricarytenoids for abductor SD (limited benefit).
Meds and DBS: no role.

34. Occupational or task specific dystonia
Late or early onset primary focal dystonia that occurs only upon performance of a specific task. Often associated with highly skillful tasks that require repetition and speed. Patients are typically affected after years of performing their offending occupation or hobby.
Examples:
hand: writer’s cramps, typist’s cramps, pianist’s dystonia, guitarist’s dystonia, golfer’s yips.
OMD: embouchure dystonia and five case reports (auctioneer, bingo caller, islamic prayer, mantra reciter, and opera singer).
Foot : very rare seen only in athletes. (remember that action dystonia of the foot in early age will often generalize into DYT1 or DYT5).

35. Occupational or task specific dystonia
Most cases tend to show symptom spread to other related tasks (become less selective) e.g. a musician with embouchure dystonia will start having problems with speaking and eating after years of pure task specific dystonia.
Many cases have an effective sensory trick at least initially.
Treatment: some cases improve with Botox but most cases will require retraining, modifying the instrument, or stopping the offending occupation altogether (to prevent symptom spread). Medications have limited role. No role for DBS.

36. Occupational or task specific dystonia

37. Points to remember
Camptocormia: is abnormal forward flexion of the trunk upon standing and walking that dissipates on lying down. Commonly seen in parkinsonian syndromes but can be isolated. Two major pathological processes: paravertebral myopathy and axial dystonia.
Dopamine blockers can cause acute secondary dystonia or tardive dystonia after years of use. common presentations include occulogyric crisis, retrocollis, and OMD. Dopaminergic meds can cause on-time or off-time dystonia\chorea.
Taking a good perinatal hx is of great importance for differentiating primary from secondary generalized dystonia in children and adolescents before deciding on DBS referral.

38. Points to remember
Wilson’s disease should be ruled out for any patient presenting with any form of dystonia before the age of 40 given the treatable nature of the condition and the serious consequences of non or maltreatment.
Levodopa trial should be used more often than not especially within the appropriate setting (any generalized dystonia with negative perinatal hx, any foot dystonia, and whenever in doubt!).

39. Common scenarios What would you do next! Levodopa trial: negative.
9 yo m pt developed action dystonia of the foot that became generalized over the course of 1 year:
What would you do next!
Levodopa trial: negative.
What’s your diagnosis
DYT1
How would you treat
DBS
9 yo m pt developed action dystonia of the foot that became generalized over the course of 1 year:
What would you do next!
Levodopa trial: positive.
What’s your diagnosis
DYT5
How would you treat
levodopa

40. Common scenarios What would you do next! What’s your diagnosis
9 yo m pt presents with generalized dystonia of long duration. Perinatal hx is positive for asphyxia. Pt is underweight and spastic.
What’s your diagnosis
Dystonic CP
How would you treat
Anticholinergics, baclofen, benzos as tolerated. PT.
50 yo m pt developed dystonia of the foot. Hx revealed a one year of hyposmia, constipation, and worsened handwriting.
What would you do next!
Neuro exam: slow finger tapping. Higher tone of the left arm.
What’s your diagnosis
Early Parkinson’s disease
How would you treat
Levodopa if symptoms bothersome. Exercise.

41. DBS for dystonia

42. DBS for dystonia
Location: bilateral stimulation of the Gpi. Unilateral stimulation is impractical in dystonia.
Indication: primary generalized dystonia. > 25% improvement in about 75% of cases.
Technique: ideally with MER but can be done under GA and MRI guidance if dystonia is quite advanced.

43. DBS for dystonia Surgical side effects: bleeding and infection.
Stimulation side effects (reversible): dysartheria, gait difficulty, other capsular SE’s if the lead was placed too medial, cognitive impairment but much less than STN DBS.
Programming: often requires high parameters (PW, F, V) » battery may need frequent replacement.

44. GPI vs STN DBS GPI STN Indication PD. Dystonia - PD Laterality
unilat or bilat for PD.
- bilat for dystonia
Unilat or bilat.
Technique
Mapping with MER or MRI guided only under GA for dystonia
Mapping with MER.
Programming
Require higher parameters for dystonia
Require less parameters
Battery life
Less in dystonia
More
Cognitive side effects
Less
Bleeding
Levodopa dose reduction in PD No
Yes

45. Thank you