35 free trades

Dystonia

-Definition: Sustained or intermittent repetitious/stereotyped muscle contractions causing

twisting/abnormal movements and/or postures, often initiated/worsened by voluntary action..

-Involve both agonist and antagonist muscles.

-Speed can be fast or slow; adult onset is usually insidious onset.

-Can vary with body position.

-Can have dystonic tremor at times, that can mimic ET.

-Worsened by stress and fatigue.

-Reduced by relaxation, hypnosis, sleep, SENSORY TRICKS.

-Can sometimes remit for weeks or months at a time (usually in first 3 years of onset).

-Usually not painful or fixed until late in the disease, when contractures form (exception is cervical
dystonia, usually painful).

-VAST majority of focal dystonias are idiopathic.

PATHOPHYSIOLOGY:

-Loss of inhibition of movement system

-Increased plasticity of neural connections

CLASSIFICATION:
Describe by age of onset, distribution, temporal pattern, other abnormalities, and etiology (2013
classification system)

1) Age:

-Infancy (birth to 2 years): usually metabolic

-Age 3-20: usually combined/generalized, usually inherited

-Age 21 and older: Usually focal or segmental, and idiopathic.

2) Distribution:
 Focal localized to a specific body part (most common)
Segmental involves 2 or more adjacent body parts (second most common)
Multifocal involves 2 or more non-adjacent body parts
Hemidystonia (Unilateral) involves arm and leg on only one side
Generalized Trunk plus two other regions

-Primary dystonia begins with focal dystonia, can then spread to be segmental or generalized
-Even in a family, some can have focal, while others have segmental or generalized types.
-Same meds can help the different types of dystonia

3) Temporal pattern:
-Persistent
-Action-induced
-Diurnal
-Paroxysmal

4) Other abnormal movements also occurring

-If not, call it primary dystonia

5) Other systemic features or other neurologic abnormalities

-If not, call it primary dystonia

6) Etiology based on neuropathology

-Structural lesion
-No structural lesion
-degenerative

7) Etiology based on inheritance vs. acquired

-Inherited (AR, AD, X-linked, mitochondrial)
-Acquired
-Idiopathic

CAUSES OF DYSTONIA:
1) Genetic
See: http://www.cmdg.org/Dystonia/Dystonia_genetics/dystonia_genetics.htm
A) Some isolated genetic dystonias:
Childhood onset:
-DYT1: Focal, segmental, or generalized. Early onset (mainly < age 20).Limbs (usually legs)
involved first, and then MAY (but not always) spreads to become generalized. Younger age +
leg as site of onset= more likely it will spread. AD but 30-40% penetrance.Ashkenazi
Jews.TOR1A gene.

-DYT2: AR. Gene unknown.RARE.

-DYT6:Generalized>segmental or focal. Usually starts arm or neck/cranial, usually remains

upper body (as opposed to DYT1). Speech is usually affected. AD but 60% penetrance.Can
occur up to age 49.THAP1 or DYT6 gene.
-DYT 13:Craniocervical and upper limb >>generalized. Onset first or second decade.AD but
60% penetrance.Gene unknown.
-DYT 17: Focal, and eventually segmental and then generalized. Onset teenager.AR, gene
unknown.RARE.

Adult onset:
-DYT 7: Focal. AD, gene unknown.RARE.
-DYT 21: Blephrospasm, upper limb, cervical, and spasmotic. AD, gene unknown.RARE.
-DYT 23: Cervical. AD, CIZ1 gene.
-DYT 24: Cervical > laryngeal > arms; legs never involved. Often with tremor.Onset childhood
to 40s.AD, ANO3 gene.
-DYT 25: Cervicocranial + spasmotic dysphonia, +/- generalization. AD, GNAL gene.

B) Some Dystonia Plus genetic syndromes:

-DYT3 (dystonia-parkinsonism, Lubag syndrome): Focal dystonia first (lower limbs >upper
limbs >craniofacial, then generalizes), then later dystonia is replaced by parkinsonism. X-linked
AR, TAF1 or DYT3 gene.Filipino.

-DYT 4: Whispering dysphonia, but widely variable presentation. Responds to alcohol.AD,

TUBB 4 gene.RARE.

-DYT5 (dopa-responsive dystonia): Starts in legs with toe walking usually in childhood, 50%
are specifically worse at night, parkinsonism, markedly improved with low-dose dopamine (50-
200mg per day), no pathologic neurodegeneration; normal PET/SPECT. Adult onset more
neck focal dystonia. Not get dyskinesia/wearing off. AD (GCH1 gene) or AR (TH gene).RARE.

-DYT 11 (Myoclonus Dystonia): Usually involves upper body (writers cramp or cervical
dystonia), legs spared. Slowly progressive, plateaus.Responds to alcohol.Variable age of
onset, usually first or second decade.AD, SGCE gene.Variable penetrance.

-DYT12: (rapid-onset dystonia parkinsonism). Evolves to generalized dystonia-parkinsonism in

hours to weeks, then plateaus.More severe superiorly compared to inferiorly. Adolescence to
adult onset. No response to levodopa. AD, ATP1A3.VERY RARE.

-DYT 15: Axial/proximal arm myoclonus, some dystonia. Childhood onset.Improves with
alcohol.AD, reduced penetrance.RARE.
 -DYT 16: Focal limb dystonia in children, then generalizes; also sardonic smile, dysphagia,
dysarthria, and sometimes parkinsonism. AR, PRKRA gene.Brazilian.RARE.

C) Paroxysmal dystonias:
-DYT 10 and DYT 19: Paroxysmal kinesigenic dyskinesia: Triggered by sudden movement. Short-lasting
and frequent. Phenytoin or carbamazepine is treatment. Associated gene: PRRT2.

-DYT 8 and 20: Paroxysmal NON-kinesigenic dyskinesia: NOT triggered by movement, but by other
triggers or at rest spontaneously. Long-lasting and infrequent.Klonopin is treatment. Associated gene:
MR-1.

-DYT 18: Paroxysmal exercise-induced dyskinesia: Triggered by SUSTAINED exercise/physical exertion.

Treatment not great. Associated gene: SLC2A

2) Idiopathic
Blepharospasm(trick: speak or remain silent, look down, touch corner of eye;
worse with blinking or bright lights, looking up, reading; mean age 60)
Cervical Dystonia (torticollis,antero/retrocollis, laterocollisetc; frequently painful;
mean age 40)
Meige syndrome (cranial facial dystonia; upper and lower face dystonia)
Occupational/Task specific dystonia (ie, writer's cramp)
Focal limb dystonia (usually task-specific; lower extremity dystonia in kids usually
generalizes; in adult leg dystonia may suggest structural lesion or PD; lower
extremity dystonia can be improved when walking backwards)
Spasmotic dysphonia (vocal cords; adductor vs. abductor; mean age 30-50)
Oromandibular dystonia: (trick: toothpick in mouth, bite on hard object, touch
bottom of jaw; mean age 60).
Task specific: Writers cramp (trick: hold pen in novel way), Musician cramp,
golfer cramp, etc

3) Secondary
Tumor, stroke, MS, trauma, or other mass or structural lesion
Tardive dystonia 2/2 meds
Neurodegenerative disease (Parkinson's, MSA, PSP, CBD, Huntington's, Wilsons,
neuroacanthocytosis)
Encephalitis
Paraneoplastic
Anti-phospholipid antibody

4) Fixed (posture) dystonia:

Most are psychogenic. Non-changing with change in body posture, cant be altered by examiner.
Need to examine under sleep (if absent in sleep, usually psychogenic); CAN still cause contractures.

5) DDx: Structural (MSK, masses, skeletal deformities, etc)

Workup
-Characterize the dystonia as above, do a good neuro/movement disorders history and exam, and
then try to establish if genetic vs. isolated focal dystonia vs. dystonia + other
features/generalized/weird
A) Genetic: What mode of inheritance based on history? See what genetic dystonia syndrome this
would be consistent with. Get MRI brain. Consider genetic testing (AFTER genetic counseling) if
clear family history or clear DYT syndrome.
B) Isolated focal dystonias: Get MRI brain and (if onset < age 40) Wilsons labs; otherwise no further
workup.
C) Dystonia + other features/generalized/weird: Get MRI brain. Consider ancillary testing (for Wilsons,
paraneoplastic, etc). Check medication list for offending agents.

Treatment:
1) General points:
-Identify treatable cause (Wilsons, drugs, structural lesions, metabolic abnormalities)
-If no treatable cause, treatment is symptomatic.
-Education/genetic counseling
-Address comorbidities (depression, etc)
-Explain treatment is symptomatic, not curative or protective.
-Select treatment according to severity, age, type, and distribution
-Encourage patients to discover sensory tricks.
-Range of motion exercises to present contractures. DO NOT use immobilization techniques.
-L-dopa in young dystonia
-Surgery as last resort.
-Check out https://www.rarediseasesnetwork.org/Dystonia/professional/treatment/index.htm

2) PHYSICAL, SUPPORTIVE, AND ANCILLARY:

-PT (prevent contractures, range of motion exercises) and OT (adaptive devices for sensory tricks,
etc)

3) DRUGS/SURGERY:
 A) GENERALIZED DYSTONIA
0.5) **Always try Levodopa (Sinemet) trial to rule out dopa-responsive dystonia if
younger-onset or parkinsonism.
1) Anticholinergics:First line for generalized dystonia. Artane (trihexyphenidyl) start 1mg
BID, increasing SLOWLY over MONTHS up to as much as 80-140mg/day over LONG time.
DO NOT stop suddenly, requires slow taper. Side effects include dry mouth, urinary retention,
constipation, memory loss, confusion, blurry vision, worsening of glaucoma; can treat these
symptomatically. Avoid in old patients, or patients with cognitive concerns.
2) Tetrabenazine (dopamine depleting);12.5 mg daily, increase to 50-75mg daily.
3) Antipsychotics
4) Anticonvulsants (carbamezapine, pregabalin, leviteracitam, zonisamide)
5) Muscle relaxants (benzos, flexiril, baclofen/pump)
6) Levodopa
7) Deep brain stimulation: Best for medically refractory genetic or idiopathic generalized or
segmental dystonias (ie, DYT1). NOT a cure. Predictors of success are primary dystonia,
younger age of onset, short disease duration, and less severity. Currently GPi is the preferred
location (more studied), but STN may have less bradykinesia.

B) FOCAL DYSTONIA
-Botox, Botox, Botox (first line for focal or segmental dystonias) light chain cuts proteins
at presynapse, keeps Ach from being released from presynapse (See Evidence based review
and assessment of botulinum neurotoxin for the treatment of movement disorders by Hallett et
al. for specific toxin for each condition). Generally continues to work in the long-term without
wearing off

ADDITIONAL NOTE ON STATUS DYSTONICUS: severe generalized stiffness, fever, markedly

elevated CK, respiratory, renal problems. Versed gtt add propafolpentobarb coma baclofen
infusion surgery, DBS