a slide on movement disorder

1. Avinash Chandra
Annapurna Neurological Institute

2. Dystonia= Dys+ tonia
3rd most common movement disorder
Cooper and Spindler, Neurological Cases Vol.2 No.3
October 2015
1830’s Case published in 1830s era up to 1864s as ‘writer’s cramp’ Scrivener’s
Palsy………….
1864- 1888
-Modern Wilson’s disease possibly described by William G.
in 1888 as `tetanoid chorea’ (Britain)
-1887 case published as ‘wry neck’
-1864Cases of ‘blepharospasm , oromandibular dystonia’ published
by Hartio (Britain)
1911
-Coined by Oppenheim (Germany) from case series on Jewish children from
Russia and others “muscle spasm and twisting postures’ named-
“dystonia musenliform deformans’
-Shalbe and later his Prof. Ziehan (France) published case series as
“Torsion Neurosis”
-Flatau and Sterling (Poland) published case series as “progressive torsion spasm”

3. Dystonia
• New definition prepared with the convention of
movement disorder specialists, MDS, MDRF
• Defined as Movement disorder characterized by
sustained or intermittent muscle contraction
(often same) causing abnormal, often repetitive
movement , posture or both.
• MDS and MDRF 1984-2014
consensus
Normal Blink Tonic Blink

4. Classification

5. Classification in Evolving
• An increasing appreciation of the varied clinical manifestations and causes for
dystonia over the years leading to varying proposals

6. Two Axes

8. Phenomenology
In children:
• Starts in a limb
• Rarely starts in the face or neck
• Typically spreads to the rest of the body to
become generalized
In adults:
• Starts in the face, neck or limb
• May spread to nearby muscle group (e.g., neck to
the face)
• Rarely spread to become generalized

9. Some common and interesting Dystonias

10. Case-1

11. Case-2

12. Case-3

13. Case-4

14. Axis II: Etiology
• Pathology: A structural lesion is likely to cause a
static course, while genetic might have a variable
course.
• Inheritance may be autosomal dominant,
autosomal recessive, X-linked, or mitochondrial. If
no family history is present, dystonia is considered
sporadic.
• DYT genetic descriptions are widely used in
dystonia nosology (with some changes in 2013)
and we will include these in the descriptions of
selected dystonias

15. Some common and Interesting dystonias
• Primary Torsion Dystonia (Oppenheim dystonia) The
first identified genetic cause of early-onset
generalized dystonia is DYT1, caused by Torsin 1A
gene mutation, autosomal dominant, penetration
of about 30%.
• DYT6 is another autosomal dominant dytonia with
lesser penetrance and genetic mutation in THAP1
gene manifesting as cranio cervical or upper limb
dystonia and occassionally to generalized form

16. • Dystonia with Parkinsonism- Dopa responsive
dystonia (mostly).
DYT5 dystonias/Seagaawa’s are due to a deficiency
within the dopamine synthesis pathway, GTTP
cyclohydroxylase gene (chr. 14q34).
The most salient clinical features of DRDs are
diurnal fluctuations and a robust response to
levodopa. In adults, it presents as a focal or
multifocal dystonia, and or parkinsonism.
Rieder C., Arq Neuropsiquiatr, 2015

17. Acquired (Secondary) Dystonias
• Drug-induced (D2 blockers, flecainide)
• Structural (post traumatic)
• Toxic (Mn, CO, CS2, Hymenoptera)
• Metabolic
• DRD - TH deficiency, sepiapterin, GCH-deficiency
• Lesch-Nyhan
• PKAN
• NBIA
• Psychogenic

18. Pathophysiology
• Not well understood yet. The primary
neurophysiologic mechanisms considered to be
important in dystonia pathogenesis include
decreased cortical inhibition, increased cortical
excitability, abnormal sensory processing, and
maladaptive cortical plasticity.
• Hemidystonia affects half of the body and is
usually associated with structural impairment of
contralateral basal ganglia (putamen)
Dystonia Pathophysiology Reviewed- MDS

20. Diagnosis of Dystonia
◆History:
age at onset, pattern and progression of the
dystonia, the family history, and the associated
neurological symptoms (such as tremor, pain…)
• Video from caregiver for paroxysmal dystonias
◆ Physical exam:
observe dystonic movements and postures and
other associated neurological signs (such as
parkinsonism and myoclonus)

21. ◆ Imaging of brain and/or spine to rule out:
Anatomical lesions, metal or calcium deposition,
caudate atrophy, white matter changes...
◆ Blood, urine, and cerebrospinal fluid amino acid
levels in children
◆ Abnormal CSF glucose, lactate, and pyruvate point
to a mitochondrial disorder (may be confirmed by
genetic testing or a muscle biopsy)
◆ Nerve conduction studies rule out neuropathy
(such as in spinocerebellar ataxia,
neuroacanthocytosis, or metachromatic
leukodystrophy)

22. Approach to Treatment
• Etiology-specific:
treatment of underlying
disease
• Anatomy-specific: treat
sensory, basal ganglia,
frontal, or cerebellar
origin
• Nonspecific: reduce
stretch reflexes

23. Treatment Options
• Treatment for dystonia consists of medications,
chemodenervation, and surgical therapies
• Anticholinergics (generalized dystonia, children)
• Dopamine agonists or levodopa
• GABA agonists (A and B, also intrathecal- cervical
dystonia)
• Other anticonvulsants
• VMAT inhibitor
• Botulinum toxins
• Surgical (Myectomy, SDR, DBS, thalamotomy)

24. Treatment Options
Anticholinergics
• Burke and colleagues found a clinically significant
improvement in 71% of 31 patients (mean age 19
years) on an average daily dose of 30 mg daily
during a 36-week study period.
• Can be started at 1 mg daily and increased by 1
mg every 3 – 5 days over a period of 1 month to a
goal dose of 2 mg t.i.d.
Cloud et al. Treatment strategies of dystonia, Expert Opin
Pharmacother 2012

25. Treatment Options
GABA agonist
• Baclofen is a presynaptic GABA receptor agonist
primarily used to treat spasticity. The exact
mechanism by which it helps in dystonia is not
known.
• In retrospective studies, 20% of patients with
various forms of dystonia had a good response
• Baclofen should be administered in 3 – 4 divided
daily doses. A typical starting dose is 5 mg daily.
Increasing by 5 mg/day every 3 – 5 days is
generally reasonable Cloud et al. Treatment strategies of
dystonia, Expert Opin Pharmacother 2012

26. Treatment Options
Benzodiazepines
• Often used in the dystonias, despite the fact that
their efficacy has not been evaluated in any large,
controlled studies.
• Clonazepam is the most frequently used in
Blepharospasm. In an open study, clonazepam and
other benzodiazepines were found to be beneficial
in 16% of patients with various types of dystonia
• A typical starting dose is 0.5 mg of clonazepam in
the evening. The dose is slowly increased to an
average daily dose of 1 – 4 mg divided t.i.d.

27. Treatent Option
Tyrosine Hydroxylase
TH converts Tyr to DOPA
• Tetrahydrobiopterin is cofactor
– GTP cyclohydrolase (GCH)
– 6-pyruvoyltetrahydropterin synthase (PTPS)
– Sepiapterin reductase (SR)
• Tetrahydrobiopterin also affects metabolism of
nitric oxide, serotonin, and phenylalanine
• Sapropterin is FDA approved for PKU

28. Tetrabenazine
• Inhibits Vesicular Monoamine Transporter 2
• Typical starting dose = 6.25mg bid
• Typical effective dose = 25mg bid
• Metabolism affected by CYP2D6
• FDA approved for Huntington’s Chorea
• Also effective for tardive dyskinesia and some
dystonias
• Sleepiness and depression are major SE’s

29. Botulinum Toxin
• Inhibits presynaptic Ach release by destroying
SNARE proteins
• Dosing can be tricky
• FDA approved for cervical dystonia,
blepharospasm, and a few other disorders
• Typical duration of action = 90-120 days
• Weakness is the major SE
• Four current formulations: 3 A and 1 B

30. • Medicine is a living science. In order to thrive
and grow it must adapt as new information is
obtained from both bench side and bedside
research.