Ultrasound-Guided Chemodenervation Procedures

Ultrasound-Guided
Chemodenervation
Procedures
Text and Atlas
Katharine E. Alter, MD
Mark Hallett, MD z Barbara Karp, MD z Codrin Lungu, MD
New York

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Ultrasound-guided chemodenervation procedures : text and atlas / Katharine E. Alter . . . [et al.].
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-936287-60-4 — ISBN 978-1-61705-107-4 (e-book)
I. Alter, Katharine E.
[DNLM: 1. Botulinum Toxins—therapeutic use. 2. Nerve Block—methods. 3. Ultrasonography—methods.
QV 140]
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2012047617
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12 13 14 15 / 5 4 3 2 1

iii
Contributors v
Illustrators vii
Introduction ix
I. Neurotoxins Review 1
1. Pharmacology and Physiology 2
Mark Hallett and Barbara Karp
2. Toxin Handling, Reconstitution, and Dilution 10
Codrin Lungu and Mark Hallett
II. Clinical Applications 15
3. Focal Dystonia of the Upper Extremity 16
Barbara Karp and Mark Hallett
4. Truncal Dystonia and Other Truncal Dyskinesias 20
Barbara Karp and Mark Hallett
5. Cervical Dystonia 24
Codrin Lungu and Mark Hallett
6. Hemifacial Spasm 28
Codrin Lungu and Mark Hallett
7. Lower Limb Dystonia 30
Katharine E. Alter and Fatta B. Nahab
8. Upper Motor Neuron Syndromes 36
Katharine E. Alter and Fatta B. Nahab
9. Hyperhidrosis 46
Codrin Lungu and Mark Hallett
10. Botulinum Toxin Therapy for the Treatment of Sialorrhea 48
Katharine E. Alter, Zachary Bohart, and Codrin Lungu
III. Ultrasound Basics 55
11. Physics of Ultrasound Imaging 56
Siddhartha Sikdar
12. Instrumentation and Knobology 84
Katharine E. Alter and Steven M. Skurow
Contents

MARK HALLETT, MD
BARBARA KARP, MD
CODRIN LUNGU, MD
MARK HALLETT, MD
BARBARA KARP, MD
CODRIN LUNGU, MD
13. Ultrasound for Procedural Guidance: Scanning—Techniques and Tips 108
Katharine E. Alter, Michael C. Munin, and Steven M. Skurow
14. Chemodenervation: Ultrasound Characteristics of Relevant Tissues 124
Katharine E. Alter, Stephen Nichols, and Steven M. Skurow
15. Comparing Guidance Techniques for Chemodenervation Procedures 138
Katharine E. Alter and Michael C. Munin
16. US-Guided Neurotoxin (BoNT) Injections: Clinical Applications 154
Katharine E. Alter and Michael C. Munin
17. Ultrasound Guidance for Nerve and Motor Point Blocks 170
Katharine E. Alter and John L. Lin
IV. Anatomic and Procedural Atlas 185
Nicole A. Wilson and Katharine E. Alter
Head and Neck 186
Trunk 220
Upper Limb 222
Hand 284
Lower Limb 298
V. Muscle Layers and Injection Points Atlas 341
Abrahm Behnam
Face Anterior 342
Face Side 344
Neck Front 347
Neck Side 358
Forearm 369
Hip 379
Hamstrings 395
Lower Leg 400
Posterior Neck/Back 407
Glossary 413
Index 421
iv
CONTENTS

CONTRIBUTORS
Katharine E. Alter, MD
Medical Director, Rehabilitation Programs
Mt. Washington Pediatric Hospital
Baltimore, Maryland
Senior Clinician
National Institutes of Health
Bethesda, Maryland
Zachary Bohart, MD, MS
Associate Director, Spasticity Program
Director, Neurorehabilitation Clinic
Braintree Rehabilitation Hospital
Braintree, Massachusetts
Clinical Instructor
Physical Medicine & Rehabilitation
Tufts University School of Medicine
Boston, Massachusetts
Mark Hallett, MD
Chief, Medical Neurology Branch
National Institute of Neurological Disorders and Stroke
Bethesda, Maryland
Barbara Karp, MD
National Institute of Neurological Disorders and Stroke
Bethesda, Maryland
John L. Lin, MD
Assistant Professor Emory University, School of Medicine
Internal Medicine, Physiatry, Spinal Cord Medicine Shepherd Center
Atlanta, Georgia
Codrin Lungu, MD
Clinical Fellow, Human Motor Control Section
Division of Intramural Research
National Institute of Neurological Disorders and Stroke
Bethesda, Maryland
Michael C. Munin, MD
Professor
Department of Physical Medicine and Rehabilitation
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania
Contributors

vi
CONTRIBUTORS
Fatta B. Nahab, MD
Departments of Neurology & Neuroscience
University of Miami Miller School of Medicine
Miami, Florida
Stephen Nichols, MD
Attending Staff Physician
Mt. Washington Pediatric Hospital
Baltimore, Maryland
Siddhartha Sikdar, PhD
Assistant Professor
Departments of Bioengineering and Electrical and Computer Engineering
George Mason University
Fairfax, Virginia
Steven M. Skurow, DC, FACO, RVT, RDMS
Medical Director, Terason Ultrasound
Burlington, Massachusetts

ILLUSTRATORS
vii
Nicole A. Wilson, PhD
Part IV—Anatomic and Procedural Atlas
Principal, Roth Affi nity
Chicago, Illinois
Abrahm Behnam, MD Candidate
Part V—Muscle Layers and Injection Points Atlas
Virginia Commonwealth University School of Medicine
MS Biomedical Engineering, Virginia Tech and Wake Forest University
BS Engineering Science and Mechanics, Virginia Tech
Richmond, Virginia
Illustrators

(Trang không có chữ)

From its initial ophthalmologic indications, the number of approved, accepted, and
proposed uses for botulinum neurotoxin (BoNT) therapy has expanded to include a
large number of applications for various body systems. At the same time, developments
in the fi eld of ultrasound (US) including high frequency linear transducers technology
have led to the rapid expansion of US for both diagnostic imaging and procedural guid-
ance. This expanded use of US for clinical and for research purposes is owed not only
to technological advances, but also to the increased portability and reduced cost of US
equipment. In addition, physicians increasingly recognize the many benefi ts that US
provides when used for procedural guidance, including the reduced risk of harm to
patients, the absence of ionizing radiation, and the lower cost of US when compared
to other imaging guidance techniques. An indisputable advantage of US is its dynamic
nature that provides real-time tracking of a procedure, assessment of patients during
provocative maneuvers, and the fl exibility of taking a portable US into the clinic, hospi-
tal room, or other setting for evaluations and procedures.
Physicians who perform chemodenervation procedures have long recognized the
limitations of standard techniques used to localize muscles or nerves. This has led an
increasing numbers of physicians to explore and promote US imaging as a practical
and more accurate alternative guidance technique for these procedures. Although there
numerous texts and atlases specifi c to the subject of musculoskeletal ultrasound and for
the subject of neurotoxin therapy/chemodenervation, there is limited reference mate-
rial for physicians on ultrasound guidance for chemodenervation including neurotoxin
therapy. Until recently, it has also been diffi cult for physicians to fi nd reference material
or hands on training specifi c to this topic.
The purpose of this Atlas is to provide a review of neurotoxin therapy with a strong
emphasis on ultrasound technology and its applications for chemodenervation. We
hope the material presented in this text/DVD will reduce at least one barrier that phy-
sicians encounter when trying to add US-guided chemodenervation procedures in the
clinic. The text section of this book is provided as an introduction or review of US tech-
nology, scanning techniques and image optimization required for US-guided neuro-
toxin/chemodenervation. The illustrated print and DVD Atlas sections should serve
as a reference manual for physicians to be used during US-guided chemodenervation
procedures.
The authors hope the material provided in this multimedia text will serve to edu-
cate clinicians, expand their knowledge of US and chemodenervation focused on BoNT
therapy and reduce the risks inherent in these procedures and enhance patient care.
Katharine E. Alter, MD
Mark Hallett, MD
Introduction

(Trang không có chữ)

PART I
Neurotoxins Review
1. Pharmacology and Physiology
2. Toxin Handling, Reconstitution, and Dilution

Trunk
Mark Hallett and Barbara Karp
Botulinum neurotoxin (BoNT) is one of the most deadly poisons and also one of the
most versatile medications for all of medicine (1–4). First established at the neuromus-
cular junction, but then at other nerve terminals, BoNT reduces the physiological release
of neurotransmitters and other substances. When this release is pathologically exces-
sive, BoNT can reduce release and improve symptoms. Of course, particularly at some
neuromuscular junctions, such as the diaphragm, neurotransmission is critical to sup-
port life—hence, too much BoNT can kill.
BoNT is a polypeptide with a molecular weight of 150 KDa produced by the bac-
terium Clostridium botulinum. After the polypeptide is made, it is broken into two
parts by a process called nicking, and the resultant peptide has a light (50 KDa) and
a heavy chain (100 KDa), which remain connected by a disulfi de bridge (Figure 1.1)
(5). Sequence differences in the polypeptide produced by different strains of bacteria
produce different serotypes of toxin, referred to as types A, B, C1, D, E, F, and G (6).
The different serotypes have slightly different modes of action and can evoke different
immunological responses. Even a single serotype can have versions with slightly differ-
ent peptide sequences. For example, type A has two commonly recognized forms, A1
and A2. Interestingly, BoNT is closely related to tetanus toxin, which also has its effects
by blocking synaptic release.
Synaptic release is a complex process, which is understood in considerable detail
(Figure 1.2). Neurotransmitters, such as acetylcholine, are stored in the cytoplasm of the
presynaptic ending in membrane-bound vesicles. Upon nerve stimulation, the vesicles bind
to the presynaptic nerve membrane and release the neurotransmitter into the synaptic cleft.
There are polypeptide chains that extend like hairs from the synaptic vesicle and other poly-
peptide chains extending on the inner surface of the presynaptic membrane. Docking of the
synaptic vesicle onto the presynaptic membrane requires specifi c binding of certain proteins
from each structure. These proteins collectively are called the SNARE proteins. A protein
on the vesicle is synaptobrevin (or VAMP), and two proteins on the presynaptic membrane
are syntaxin and SNAP-25. The action of BoNT is to cleave, by enzymatic action, specifi c
SNARE proteins and make synaptic release impossible. The action of BoNT is to cleave, by
enzymatic action, specifi c SNARE proteins . . . (7). For example, Type A cleaves SNAP-25,
and Type B cleaves synaptobrevin (Table 1.1).
Botulinum toxin can work only when it gets to the synaptic cleft, and medicinally it
gets there by careful injection. The heavy chain of the BoNT molecule is responsible for
binding to the outer side of the presynaptic membrane (Figure 1.2) (8). BoNT binds to
a combination of a ganglioside and a specifi c protein receptor. For BoNT-A, the protein
receptor is synaptic vesicle protein 2 or SV2 (5). Aided by a portion of the heavy chain,
the presynaptic membrane invaginates making an endocytotic vesicle and translocating
1
Pharmacology and Physiology

1. PHARMACOLOGY AND PHYSIOLOGY
3
the toxin into the cell. In the cell, the light chain separates from the heavy chain, goes
into the cytoplasm and does its damage on the SNARE proteins. The poisoning of the
ending will be ended only when the toxin is fi nally metabolized and the SNARE pro-
teins regenerate. For BoNT-A at the neuromuscular junction, this takes months.
A very small amount of the toxin is transported retrogradely into the cell body
and some can spread out of the original neuron (9,10). Some of the toxin is inac-
tivated, and the amount is so small anyway that this phenomenon has no clinical
consequence. On the other hand, even with focal injections into muscle, some of the
toxin does get into the blood stream and with high doses there can be some systemic
effects. For example, rare side effects might be mild generalized weakness or gall
bladder dysfunction (11). More importantly, there can be local spread of toxin. A
common complication, for example, would be dysphagia after injection of cervical
muscles for cervical dystonia.
More toxins will be taken up at the neuromuscular junction when the junction is
active (12). This phenomenon leads to some of the benefi cial action of BoNT because
more toxins will be taken up by those nerve endings that are participating more in the
pathological overactivity.
Figure 1.1 Protein structure of BoNT.
(A) Linear diagram of the dichain acti-
vated BoNT molecule consisting of a
light chain (LC) and heavy chain (HC)
connected by a single disulfi de bond.
HC is divided into an N-terminal
translocation domain (HCT) and a
C-terminal receptor-binding domain
(HCR).
(B)
Ribbon
diagram
of
BoNT-A.
Source: Adapted from Ref. (5) with permission.

ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES
4
At the neuromuscular junction, some recovery of function begins when the presyn-
aptic nerve sprouts new terminals and reinnervates the muscle. These new terminals
operate on newly formed postsynaptic regions. However, these new junctions are only
temporary. When the BoNT effect is fi nished, the original ending is restored and the
new junctions are eliminated. The muscle and its neuromuscular junctions return to
baseline state (13).
When dealing with muscle, much of the effect of BoNT is due to muscle weakening,
but there is another interesting effect. Muscle spindles are sensory organs in skeletal
Figure 1.2 The mechanism of synaptic release and blockade by BoNT. The left side of the fi gure shows
the normal release of acetylcholine at the neuromuscular junction. Binding of BoNT is shown on the right
side, with internalization and release of the LC into the cytoplasm. The middle portion shows the cleav-
age of SNAP-25, which leads to the inability of the synaptic vesicle to fuse and release its acetylcholine.
Source: Adapted from Ref. (9) with permission.

1. PHARMACOLOGY AND PHYSIOLOGY
5
muscle that are composed of intrafusal muscle fi bers. These fi bers are innervated by
gamma motor neurons and BoNT also weakens them (14). Stretch of muscle spindles
gives rise to sensory afferent activity, but if the spindles are slack, the sensory activity is
depressed. Reduction of this sensory activity is thought to be therapeutically useful for
dystonia and spasticity (15).
The bacterium does not make “raw” toxin, but manufactures it along with some com-
plexing nontoxic proteins, some of which are hemagglutinating. The proteins are either
150KDa or 300 KDa of molecular weight and tend to dimerize. Thus, a single complex
of BoNT might have a weight of 900 KDa if dimerized with two 300 KDa proteins.
Additionally, when prepared commercially, excipients, including albumin, sucrose and
lactose, may be added for stabilization and pH adjustment. Thus, the fi nal therapeutic
product is composed of not only of toxin itself, but also complexed proteins and excipi-
ents (16).
There are a number of commercial products available, several of type A and one type
B (Tables 1.2 and 1.3). In the United States, there are three type A toxins and one type B
toxin. These can be referred to by either generic or brand name. Some of the other sero-
types have been tested in humans, but only in limited experiments.
The potency of BoNT is measured in mouse units (mu). A mouse unit is the LD50 in
female Swiss-Webster mice. In theory, it might be possible to switch toxin preparations
by matching the dose. However, units may well be different for different products, and
Table 1.1 The different types of BoNT and their
mode of action on the SNARE proteins
Type
SNARE protein cleaved
A
SNAP-25
B
Synaptobrevin
C1
Syntaxin and SNAP-25
D
Synaptobrevin
E
SNAP-25
F
Synaptobrevin
G
Synaptobrevin
Table 1.2 Composition of commercial BoNTs
Type
Generic Name
Brand Name
Manufacturer
Composition
A
OnabotulinumtoxinA
Botox
Allergan
Dimerized with two 300
KDa proteins
A
AbobotulinumtoxinA
Dysport
Ipsen
Dimerized with two 300
KDa proteins
A
IncobotulinumtoxinA
Xeomin
Merz
Just toxin without
proteins
B
RimabotulinumtoxinB
Myobloc (in USA)
NeuroBloc (in rest of
world)
US WorldMed
Dimerized with two 150
KDa proteins

ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES
6
Table 1.3 Properties of the commercial BoNTs taken from package inserts
Name
Properties
OnabotulinumtoxinA
Sterile lyophilized form of botulinum toxin type A, purifi ed by acid precipi-
tations to a crystalline complex containing toxin and other proteins.
Supplied as 100 Units or 200 Units vacuum-dried powder. Reconstitution
only with sterile, nonpreserved 0.9% sodium chloride. Each vial contains
either 100 Units of Clostridium botulinum type A neurotoxin complex,
0.5 mg of albumin human, and 0.9 mg of sodium chloride; or 200 Units
of Clostridium botulinum type A neurotoxin complex, 1 mg of albumin
human, and 1.8 mg of sodium chloride in sterile, vacuum-dried form with-
out preservative.
Unopened vials require refrigeration (2°C–8°C, up to 36 months for 100
Units vial; up to 24 months for 200 Units vial). Administer within 24 hours
of reconstitution; store reconstituted Botox in a refrigerator.
AbobotulinumtoxinA
Purifi ed by a series of precipitation, dialysis, and chromatography steps.
The neurotoxin complex is composed of the neurotoxin, hemagglutinin
proteins, and nontoxin nonhemagglutinin protein.
Supplied as single-use, sterile 3 mL glass vial. Each vial contains 500 or 300
Units of lyophilized abobotulinumtoxinA, 125 mg human serum albumin
and 2.5 mg lactose.
Must be stored under refrigeration at (2°C–8°C or 36°F–46°F). Protect from
light. Administer within 4 hours of reconstitution; during this period keep
refrigerated. Do not freeze after reconstitution.
IncobotulinumtoxinA
Active ingredient is separated from proteins to yield active neurotoxin with-
out accessory proteins.
Supplied as a sterile white to off-white lyophilized powder to be recon-
stituted with 0.9% saline for injection. One vial of Xeomin contains 50 or
100 Units of incobotulinumtoxinA, 1 mg of human albumin, and 4.7 mg
sucrose.
Unopened vials can be stored at room temperature 20°C to 25°C (68° F–77°
F), in a refrigerator at 2°C to 8°C (36°F–46°F), or a freezer at −20°C to −10°C
(−4°F–14°F) for up to 36 months. Administered within 24 hours.
RimabotulinumtoxinB
Neurotoxin exists as a complex with noncovalent association with hemag-
glutinin and nonhemagglutinin proteins.
Supplied as a clear and colorless to light-yellow sterile injectable solution
in single-use 3.5 mL glass vials. Each single use vial contains 5,000 Units
of botulinum toxin type B per mL in 0.05% human serum albumin, 0.01 M
sodium succinate, 0.1M sodium chloride at approximately pH 5.6. It is avail-
able as 2,500 Units (0.5 mL vial), 5,000 U (1 mL vial), and 10,000 U (2 mL
volume).
Refrigerate at 2oC to 8°C (36°F–46°F). Do not freeze or shake. May be diluted
with normal saline. Once diluted, the product must be used within 4 hours
as the formulation does not contain a preservative.

1. PHARMACOLOGY AND PHYSIOLOGY
7
the differences may even differ by indication. Hence, it is not easy to switch between
toxin formations by simple formula.
As a foreign protein, BoNT may induce antibodies, and, should this be the case, the
toxin no longer has any effect (17). Early work (with an earlier version of Botox) sug-
gested that antibodies were more common with both high doses and injections more
often than every 3 months. Giving “booster” injections at an interval of a few weeks if the
original injection did not work as well as desired was, therefore, problematic. The situa-
tion has been improved by avoiding these provocative conditions. In the case of onabot-
ulinumtoxinA, a new batch has seemed much less immunogenic. IncobotulinumtoxinA
is touted as being very unlikely to cause antibodies since all the extraneous proteins
have been removed. These days, antibody formation is not very frequent. If antibodies
develop, the switching to a different serotype is an option. For example, if a patient gets
antibodies to BoNT-A, it should be possible to get a good response to BoNT-B.
The Food and Drug Administration (FDA) has approved the different toxin prepa-
rations for some of the same indications. These are listed in Table 1.4. In subsequent
chapters, how the toxin is used in these conditions and in common off-license uses will
be described.
REFERENCES
1. Jankovic J, Albanese A, Atassi MZ, Dolly JO, Hallett M, Mayer NH, eds. Botulinum Toxin: Therapeutic Clinical Practice
& Science. Philadelphia, PA: Saunders Elsevier; 2009.
2. Truong D, Dressler D, Hallett M, eds. Manual of Botulinum Toxin Therapy. Cambridge, UK: Cambridge University Press;
2009.
3. Lim EC, Seet RC. Use of botulinum toxin in the neurology clinic. Nat Rev Neurol. 2010;6(11):624–636.
4. Esquenazi A, Novak I, Sheean G, Singer BJ, Ward AB. International consensus statement for the use of botulinum toxin
treatment in adults and children with neurological impairments—introduction. Eur J Neurol. 2010;17(suppl 2):1–8.
5. Baldwin MR, Barbieri JT. Association of botulinum neurotoxins with synaptic vesicle protein complexes. Toxicon.
2009;54(5):570–574.
Table 1.4 FDA approved uses of the different commercially
available BoNTs
Name
Indications
OnabotulinumtoxinA
Strabismus
Blepharospasm
Cervical dystonia
Glabellar lines
Axillary hyperhidrosis
Adult upper limb spasticity
Overactive bladder
Chronic migraine headache
AbobotulinumtoxinA
Cervical dystonia
Glabellar lines
IncobotulinumtoxinA
Blepharospasm
Cervical dystonia
Glabellar lines
RimabotulinumtoxinB
Cervical dystonia

ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES
8
6. Swaminathan S. Molecular structures and functional relationships in clostridial neurotoxins. FEBS J. 2011;
278(23):4467–4485.
7. Lebeda FJ, Cer RZ, Mudunuri U, Stephens R, Singh BR, Adler M. The zinc-dependent protease activity of the botuli-
num neurotoxins. Toxins (Basel). 2010;2(5):978–997.
8. Hallett M. One man’s poison—clinical applications of botulinum toxin [editorial]. N Engl J Med. 1999;341(2):118–120.
9. Restani L, Antonucci F, Gianfranceschi L, Rossi C, Rossetto O, Caleo M. Evidence for anterograde transport and tran-
scytosis of botulinum neurotoxin A (BoNT/A). J Neurosci. 2011;31(44):15650–15659.
10. Palomar FJ, Mir P. Neurophysiological changes after intramuscular injection of botulinum toxin. Clin Neurophysiol.
2012;123(1):54–60.
11. Roche N, Schnitzler A, Genet FF, Durand MC, Bensmail D. Undesirable distant effects following botulinum toxin type
a injection. Clin Neuropharmacol. 2008;31(5):272–280.
12. Chen R, Karp BI, Goldstein SR, Bara-Jimenez W, Yaseen Z, Hallett M. Effect of muscle activity immediately after bot-
ulinum toxin injection for writer’s cramp. Mov Disord. 1999;14(2):307–312.
13. Fertl E, Schnider P, Schneider B, Auff E. Remote effects of chronic botulinum toxin treatment: electrophysiologic re-
sults do not indicate subclinical remodelling of noninjected muscles. Eur Neurol. 2000;44(3):139–143.
14. Rosales RL, Arimura K, Takenaga S, Osame M. Extrafusal and intrafusal muscle effects in experimental botulinum
toxin-A injection. Muscle Nerve. 1996;19(4):488–496.
15. Abbruzzese G, Berardelli A. Neurophysiological effects of botulinum toxin type A. Neurotox Res. 2006;9(2–3):109–114.
16. Dressler D, Hallett M. Immunological aspects of Botox, Dysport and Myobloc/NeuroBloc. Eur J Neurol. 2006;13
(suppl 1):11–15.
17. Benecke R. Clinical relevance of botulinum toxin immunogenicity. BioDrugs. 2012;26(2):e1-e9.

(Trang không có chữ)

Trunk
Codrin Lungu and Mark Hallett
Each commercial preparation of botulinum toxin has specifi c guidelines for the prepa-
ration of the product prior to administration. The different BoNT formulations are not
identical or interchangeable.
In all cases, the medication is prepared immediately before administration in the
offi ce or clinic. The concentration and dosage differ between formulations and depend-
ing on the targeted structures, while injection technique is similar regardless of the for-
mulation used.
PREPARATION OF ONABOTULINUMTOXINA—BOTOX®
The medication is provided in single-use, sterile 100 Units or 200 Units vacuum-dried
powder for reconstitution only with sterile, nonpreserved 0.9% sodium chloride injec-
tion USP prior to injection (1).
To reconstitute each vial, the diluent is drawn into the appropriate size syringe and
injected into the vial. The vacuum pulls the diluent into the vials, and it is recommended
that vials that do not display this negative pressure be discarded. The dried powder is
mixed with the diluent by gently rotating the vial, and turning the vial upside down
should be avoided (2). The manufacturer recommends that the toxin be administered
within 24 hours of reconstitution, during which time it can be stored at 2˚C to 8˚C. It
is worth noting that in practice the substance is more resilient and the effi cacy more
conserved than these conservative guidelines (3), and preserved effi cacy for cosmetic
applications has been demonstrated after storage for up to 2 weeks (4).
The choice of dilution depends on the therapeutic target. If a large dose is injected
(e.g., for cervical dystonia or spasticity), the usual approach is to use 1 mL of saline/100
Units of toxin, resulting in a concentration of 10 Units/0.1 mL. When better control over
small doses is required (e.g., facial muscle injections), 2 mL/100 Units or 4 mL/100
Units can be used, resulting in concentrations of 5 and 2.5 Units/0.1 mL, respectively.
A higher dilution can theoretically cause more spread of the toxin given the higher
volume. When studied for blepharospasm applications, onabotulinumtoxinA injection
with a higher dilution was equally effi cacious, but resulted in slightly more pain and
local reactions (5). In larger muscles, larger volumes seem to show a marginal increase
in the magnitude of the paralyzing effect (6), but the concern for wider spread with
higher volumes remains.
2
Toxin Handling, Reconstitution, and Dilution

2. TOXIN HANDLING, RECONSTITUTION, AND DILUTION
11
PREPARATION OF ABOBOTULINUMTOXINA—DYSPORT®
In the United States, abobotulinumtoxinA is available in 500 Unit vials, containing pow-
der for reconstitution (7).
Each vacuum-dried vial is reconstituted with sterile 0.9% sodium chloride. The dil-
uent is drawn into the appropriate size syringe and injected into the vial. The partial
vacuum pulls the diluent into the vials, and it is recommended that vials that do not
display this negative pressure be discarded. The dried powder is mixed with the diluent
by gently rotating the vial, and turning the vial upside down should be avoided.
The manufacturer recommends administration within 4 hours of reconstitution, dur-
ing which time the product should be stored at 2˚C to 8˚C, and away from direct light.
Again, in practice it has been suggested that the preparation can maintain effi cacy for
much longer, up to 3 weeks (8), but more data would be needed to warrant a systematic
departure from the manufacturer’s guidelines.
The choice of dilution depends on the therapeutic target. With a higher dilution, more
spread of the toxin can be anticipated (9). For medium and large muscles, a common
approach is to reconstitute the 500 Unit vial with 2.5 mL of saline (10). With this formu-
lation as with others studied, larger volumes (higher dilutions) seem to spread further
in the muscles with possible increase in effi cacy but also, conceivably, side effects (11).
PREPARATION OF INCOBOTULINUMTOXINA—XEOMIN®
The substance is available as lyophilized powder for reconstitution in 50 and 100 Unit
vials (12). Each vial should be reconstituted with sterile, preservative-free 0.9% sodium
chloride injection. The diluent is drawn into the appropriate size syringe and injected
into the vial. The partial vacuum pulls the diluent into the vials, and it is recommended
that vials that do not display this negative pressure be discarded. The dried powder
is mixed with the diluent by gently rotating the vial. The manufacturer recommends
cleaning the exposed portion of the rubber stopper of the vial with alcohol (70%) prior
to insertion of the needle.
Unlike other formulations, incobotulinumtoxinA can be stored at room temperature
before reconstitution. Once reconstituted, it should be used within 24 hours, and be
stored at 2˚C to 8˚C.
The choice of dilution depends on the therapeutic target, but at least for small muscle
applications there is no suggestion that higher or lower concentrations infl uence effi -
cacy (13).
While the manufacturers of type A botulinum toxin suggest reconstitution with pre-
servative-free saline and this has been adopted in some consensus recommendations
(8), studies have shown that preserved saline does not affect the potency when tested
for some of the formulations, particularly in the case of onabotulinumtoxinA (3,14). We
are unable to recommend a different approach than the one included in the manufactur-
er’s package inserts based on the available data.

ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES
12
PREPARATION OF RIMABOTULINUMTOXINB—MYOBLOC®
RimabotulinumtoxinB is provided in a ready-to-use solution and does not require
reconstitution (15). The substance is provided as sterile injectable solution in single-use
3.5 mL glass vials. Each single-use vial of formulated rimabotulinumtoxinB contains
5,000 Units of botulinum toxin type B per mL in 0.05% human serum albumin, 0.01 M
sodium succinate, 0.1 M sodium chloride. It is available as 2,500, 5,000, and 10,000 Units
vials in 0.5, 1, and 2 mL, respectively.
Storage is recommended at 2˚C to 8˚C, protected from light, and the product is ready
to use without further reconstitution. If further dilution is desired, the toxin can be fur-
ther diluted with normal saline, in which case it should be used within 4 hours of dilu-
tion. The solution cannot be further concentrated (16,17).
The choice of needle size depends on the muscles targeted. For facial muscles, our
group and others use 30G needles, with a preferred length of 0.5 inches. For larger mus-
cles, needles with lengths between 1.5 and 2.5 inches are used, and a preferred size
between 25 to 28G (18,19). The electromyography (EMG) injection needles are manufac-
tured in a variety of sizes, from 24 to 30G. When using ultrasound guidance, thinner and
less traumatic needles are used, and we prefer the 28G size.
REFERENCES
1. OnabotulinumtoxinA. OnabotulinumtoxinA drug data. 2010;
label/2011/103000s5236lbl.pdf
2. Botox. Botox® product information. 2011;
3. Carruthers J, Fagien S, Matarasso SL. Consensus recommendations on the use of botulinum toxin type a in facial aes-
thetics. Plast Reconstr Surg. 2004;114(suppl 6):1S-22S.
4. Hui JI, Lee WW. Effi cacy of fresh versus refrigerated botulinum toxin in the treatment of lateral periorbital rhytids.
Ophthal Plast Reconstr Surg. 2007;23(6):433–438.
5. Boyle MH, McGwin G, Jr., Flanagan CE, Vicinanzo MG, Long JA. High versus low concentration botulinum toxin A
for benign essential blepharospasm: does dilution make a difference? Ophthal Plast Reconstr Surg. 2009;25(2):81–84.
6. Kim HS, Hwang JH, Jeong ST, et al. Effect of muscle activity and botulinum toxin dilution volume on muscle paralysis.
Dev Med Child Neurol. 2003;45(3):200–206.
7. Dysport. Dysport prescribing information. 2010 [cited 2010]; Ipsen Dysport® Reconstitution Information.
dysport.com/hcp/PDFs/Dysport_Reconstitution.pdf
8. Kane M, Donofrio L, Ascher B, et al. Expanding the use of neurotoxins in facial aesthetics: a consensus panel’s assess-
ment and recommendations. J Drugs Dermatol. 2010;9(suppl 1):s7-s22; quiz s3-S5.
9. Abbasi NR, Durfee MA, Petrell K, Dover JS, Arndt KA. A small study of the relationship between abobotulinum toxin
A concentration and forehead wrinkle reduction. Arch Dermatol. 2012;148(1):119–121.
10. Hefter H, Kupsch A, Mungersdorf M, Paus S, Stenner A, Jost W. A botulinum toxin A treatment algorithm for de novo
management of torticollis and laterocollis. BMJ Open. 2011;1(2):e000196.
11. Hu GC, Chuang YC, Liu JP, Chien KL, Chen YM, Chen YF. Botulinum toxin (Dysport) treatment of the spastic gas-
trocnemius muscle in children with cerebral palsy: a randomized trial comparing two injection volumes. Clin Rehabil.
2009;23(1):64–71.
12. Van Gerpen JA, Matsumoto JY, Ahlskog JE, Maraganore DM, McManis PG. Utility of an EMG mapping study in treat-
ing cervical dystonia. Muscle Nerve. 2000;23(11):1752–1756.
13. Prager W, Zschocke I, Reich C, Brocatti L, Henning K, Steinkraus V. Does dilution have an impact on cosmetic results
with BoNT/A? Complex-protein-free BoNT/A for treatment of glabella lines. Hautarzt. 2009;60(10):815–820.
14. Trindade De Almeida AR, Secco LC, Carruthers A. Handling botulinum toxins: an updated literature review. Dermatol
Surg. 2011;37(11):1553–1565.

2. TOXIN HANDLING, RECONSTITUTION, AND DILUTION
13
15. Myobloc. Myobloc prescribing information. 2010;
16. Setler P. The biochemistry of botulinum toxin type B. Neurology. 2000;55(12 suppl 5):S22-S28.
17. Callaway JE. Botulinum toxin type B (Myobloc): pharmacology and biochemistry. Clin Dermatol. 2004;22(1):23–28.
18. Anderson TJ, Rivest J, Stell R, et al. Botulinum toxin treatment of spasmodic torticollis. J R Soc Med.
1992;85(9):524–529.
19. Borodic GE, Pearce LB, Smith K, Joseph M. Botulinum a toxin for spasmodic torticollis: multiple vs single injection
points per muscle. Head Neck. 1992;14(1):33–37.

(Trang không có chữ)

PART II
Clinical Applications
3. Focal Dystonia of the Upper Extremity
4. Truncal Dystonia and Other Truncal Dyskinesias
5. Cervical Dystonia
6. Hemifacial Spasm
7. Lower Limb Dystonia
8. Upper Motor Neuron Syndromes
9. Hyperhidrosis
10. Botulinum Toxin Therapy for the Treatment of Sialorrhea

Trunk
Barbara Karp and Mark Hallett
Dystonia of the upper extremity can occur as an idiopathic focal dystonia, as part of
segmental dystonia, generalized dystonia or neurodegenerative illnesses or can arise
secondary to brain lesions, especially of the basal ganglia. Since it affects arm and hand
muscles, upper extremity dystonia disrupts daily activities and skilled performance and
is particularly disabling.
Idiopathic focal hand dystonia commonly begins in middle age. The presenting
symptom is often merely a feeling of tightness or discomfort in the hand or forearm.
Within weeks to months, dystonic abnormal movements and postures (Figure 4.1)
ensue, accompanied by loss of motor control (1). Focal hand dystonia often displays a
unique “task specifi city” in which the dystonia manifests only during particular activi-
ties, such as writing or playing a musical instrument. Interestingly, other activities using
the same muscles are spared. Task specifi city is so characteristic of focal hand dysto-
nia that the disorder is often named by the affected activity, such as “writer’s cramp,”
“musician’s cramp,” or “typist’s cramp.” Over time, however, the specifi city may be lost
and dystonic contraction may affect additional actions. When severe, dystonic postur-
ing is present at rest. The etiology and pathophysiology of focal hand dystonia have not
been fully established. Overuse or repeated fi ne hand movements may play a role in its
development and there may be a genetic predisposition in many of those affected.
Writer’s cramp is the most common form of focal hand dystonia, with a reported
prevalence of 14 per 1,000,000 in Europe and 2.7 per 1,000,000 in Rochester, Minnesota
(2,3). The estimated prevalence of musician’s cramp is 0.2% to 1% of professional musi-
cians (4,5). Unlike other focal dystonias, writer’s cramp and musician’s cramp affect
men more than women (3,4,6). Certain dystonic patterns are particularly common. For
example, idiopathic upper extremity focal dystonia affects distal hand and forearm
muscles more frequently than proximal arm and shoulder muscles, and the dominant
hand is more frequently affected than the nondominant hand. Excessive fl exion of fi n-
gers and the wrist is more frequently seen than extension, and pronation is more com-
mon than supination. When proximal muscles are affected, fl exion at the elbow is more
likely than extension along with shoulder elevation. The exact combination of involved
muscles, however, is unique to the individual and frequently involves a mix of fl ex-
ors and extensors. For musician’s cramp, the affected muscles are often small muscles,
including hand intrinsic muscles, which are relied on for playing the instrument. For
example, there is a tendency for the 4th and 5th fi ngers of the left hand in violin players
and the 4th and 5th fi ngers of the right hand in pianists to be affected.
During the evaluation of focal hand dystonia, the patient should be carefully exam-
ined to rule out an underlying peripheral neuropathy, especially ulnar neuropathy.
Neuropathies can be differentiated by the presence of weakness, atrophy, or primary
3
Focal Dystonia of the Upper Extremity

3. FOCAL DYSTONIA OF THE UPPER EXTREMITY
17
sensory loss, which are absent in focal hand dystonia. Though many patients complain
of aching or tightness in the hand and arm, overt pain is not common. If present, pain
should suggest another diagnosis, such as overuse syndrome.
Segmental upper extremity dystonia is the term used to describe dystonia of the hand,
forearm or arm together with shoulder or limb girdle involvement (Figure 4.2). A com-
mon pattern of segmental dystonia is shoulder elevation accompanied by arm adduc-
tion and internal rotation.
Focal hand dystonia seldom responds signifi cantly to nonpharmacologic therapies
such as physical therapy, occupational therapy, retraining, immobilization, or acupunc-
ture. Oral medications are similarly of only mild benefi t. Botulinum toxin injection
is presently the most effective treatment available for focal hand dystonia and upper
extremity segmental dystonia. Therefore, evaluation of those with focal hand dystonia
should focus not only on establishing the diagnosis, but also on determining involved
muscles for possible botulinum toxin injection. The identifi cation of involved muscles is
key to successful botulinum toxin treatment and relies on self-report of muscle tension
and pulling by the patient and observation of dystonic postures and movements by the
examiner. The patient should be observed at rest and during any task precipitating the
dystonia, such as writing or playing their instrument. It is often diffi cult to differentiate
dystonic movements from compensatory movements used to perform an action despite
the dystonia. About 50% of those with writer’s cramp have “mirror dystonia,” which is
provocation of dystonic posturing in the affected dominant hand when writing with the
unaffected nondominant hand. When present, mirror dystonia can demonstrate dys-
tonic posturing in the absence of compensation. For botulinum toxin injection, it may
not be necessary to inject all muscles that seem to be involved. Many patients respond
well to injection of a few muscles that seem to be key in that individual.
Figure 3.1 Writer’s cramp.

ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES
18
Botulinum toxin injection is effective in the treatment of focal hand dystonia (7).
Up to 80% of those with focal hand dystonia have more than minimal improve-
ment lasting approximately 3 months (8,9). The benefi t can be sustained for years
with repeated injection (10). Many patients achieve stability in the muscles injected.
Botulinum toxin injection has also been shown to be safe for the treatment of focal
hand dystonia. The most common adverse events are soreness at the injection site
and weakness in injected and nearby muscles. Serious adverse events are rare and
long-term adverse events, other than atrophy in injected muscles, have not been
reported.
REFERENCES
1. Sheehy MP, Marsden CD. Writers’ cramp-a focal dystonia. Brain. 1982;105(Pt 3):461–480.
2. Nutt JG, Muenter MD, Aronson A, Kurland LT, Melton LJ. Epidemiology of focal and generalized dystonia in
Rochester, Minnesota. Movement Disorders. 1988;3(3):188–194.
3. The Epidemiological Study of Dystonia in Europe (ESDE) Collaborative Group. A prevalence study of primary dysto-
nia in eight European countries. J Neurol. 2000;247(10):787–792.
4. Brandfonbrener AG, Robson C. Review of 113 musicians with focal dystonia seen between 1985 and 2002 at a clinic for
performing artists. Adv Neurol. 2004;94:255–256.
5. Altenmuller E, Jabusch HC. Focal dystonia in musicians: phenomenology, pathophysiology and triggering factors.
Eur J Neurol. 2010;17(suppl 1):31–36.
6. Duffey PO, Butler AG, Hawthorne MR, Barnes MP. The epidemiology of the primary dystonias in the north of England.
Adv Neurol. 1998;78:121–125.
Figure 3.2 Segmental dystonia.

3. FOCAL DYSTONIA OF THE UPPER EXTREMITY
19
7. Simpson DM, Blitzer A, Brashear A, et al. Assessment: Botulinum neurotoxin for the treatment of movement disorders
(an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American
Academy of Neurology. Neurology. 2008;70(19):1699–1706.
8. Karp BI, Cohen LG, Cole R, Grill S, Lou JS, Hallett M. Long-term botulinum toxin treatment of focal hand dystonia.
Neurology. 1994;44:70–76.
9. Scheuele SU, Lederman RJ. Long-term outcome of focal dystonia in instrumental musicians. Adv Neurol.
2004;94:261–266.
10. Lungu C, Karp BI, Alter K, Zolbrod R, Hallett M. Long-term follow-up of botulinum toxin therapy for focal hand
dystonia: outcome at 10 years or more. Mov Disord. 2011;26(4):750–753.

Trunk
Barbara Karp and Mark Hallett
Muscles of the trunk, including chest, back, and abdominal muscles, may be affected in
primary and secondary dystonias. Isolated dystonia of these muscles is unusual; how-
ever, the trunk is commonly and importantly involved in idiopathic generalized and
segmental dystonias (1). Truncal dystonia is present in a number of neurodegenerative
disorders including Parkinson disease, amyotrophic lateral sclerosis, and multiple sys-
tem atrophy and can be caused by a variety of medications such as acetylcholinesterase
inhibitors in patients with dementia and neuroleptics. The trunk is involved in 39% to
50% of those with cervical dystonia (2).
Truncal dystonia causes pain, distortion of posture and appearance, and functional
impairment. The postural abnormality may be positional and task-dependent or may be
present in multiple positions. The trunk twists and bends in the direction of the overcon-
tracting muscles, resulting in forward bending (Figure 4.1), back extension (Figure 4.2),
lateral bending (Figure 4.3), axial rotation, or a combination of these postures. There
may be secondary development of spine or bone degeneration, nerve impingement,
and deformation of the chest and abdominal cavities. While dystonic postures arise
from overcontraction of involved muscles, similar body postures can result from weak
antagonist muscles, which leave the agonist muscles unopposed. For example, forward
truncal fl exion can arise from weakened back extensors and can look identical to fl ex-
ion due to dystonic hypercontraction of the rectus abdominis. To choose the correct
4
Truncal Dystonia and Other Truncal Dyskinesias
Figure 4.1 Camptocormia (forward bending).

4. TRUNCAL DYSTONIA AND OTHER TRUNCAL DYSKINESIAS
21
Figure 4.2 Dystonic back extension.
Figure 4.3 Lateral trunk dystonia (Pisa syndrome).

ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES
22
therapeutic approach, it is critical that the patient be carefully examined to determine if
the postural abnormality is caused by overactivity of agonists or underactivity of antag-
onist muscles. Electromyography (EMG) and MRI of paraspinal muscles are helpful in
determining if an underlying neuropathic or myopathic process affecting antagonist
muscles is present.
Two distinctive types of truncal dystonia merit discussion: camptocormia and lat-
eral axial deviation (Pisa syndrome). Camptocormia (from the Greek for “bent trunk”)
is characterized by forward fl exion of the lumbar spine of more than 45° on standing
and walking, which abates when supine. Camptocormia may or may not be present on
sitting. The stooped posture of camptocormia develops and progresses over weeks to
months. It has been reported in 2% to 12% of patients with Parkinson disease, and may
be more common in men and in those with a longer duration of illness. It may also be
seen in patients with amyotrophic lateral sclerosis, multiple system atrophy, Tourette
syndrome, with basal ganglia lesions, secondary to neuroleptic and other mediations,
in association with trauma, arthritis or malignancies, and as a psychogenic movement
disorder (3). Some patients with camptocormia have weakness and muscle degenera-
tion or neuropathic changes in the paravertebral muscles; others, however, have normal
muscle histology. In these latter cases, camptocormia is due to dystonic overcontrac-
tion of anterior abdominal muscles. Camptocormia is generally not responsive to dopa
replacement, dopamine agonists, anticholinergics, or muscle relaxants (1). Bilateral glo-
bus pallidus (4) and subthalamic nucleus deep brain stimulation (5) have been reported
to alleviate camptocormia in some, but not all, cases.
Pisa syndrome (lateral axial deviation) describes involuntary lateral fl exion of the
trunk usually with axial rotation (6) (Figure 4.3). It often arises as a tardive syndrome
associated with the use of antipsychotic medications, and therefore can sometimes be
treated by lowering the neuroleptic dose, stopping, or switching antipsychotic medica-
tion or by anticholinergic medications. Deep brain stimulation may help alleviate lateral
axial deviation in Parkinson disease (7).
Severe truncal or axial dystonias may be best treated by oral medications, intrathe-
cal baclofen, and/or deep brain stimulation. Botulinum toxin is usually not feasible
in severe cases as toxic doses would be required to treat the multiple large and strong
axial muscles involved. Botulinum toxin has been used to treat mild-to-moderate
truncal and axial dystonia with variable success. For lateral axial dystonia, botuli-
num toxin is injected into the paraspinal muscles ipsilateral to the lateral fl exion (8).
For camptocormia, the toxin is most frequently injected into the rectus abdominis (9).
In some patients with forward fl exion or twisting, the iliopsoas may also be injected
(10). Truncal extension dystonia is treated by toxin injection into paraspinal muscles
bilaterally (11).
REFERENCES
1. Bhatia KP, Quinn NP, Marsden CD. Clinical features and natural history of axial predominant adult onset primary
dystonia. J Neurol Neurosurg Psychiatry. 1997;63:788–791.
2. Jankovic J, Leder S, Warner D, Schwartz K. Cervical dystonia: clinical fi ndings and associated movement disorders.
Neurology. 1991;41(7):1088–1091.
3. Finsterer J, Strobl W. Causes of camptocormia. Disabil Rehabil. 2011;33(17–18):1702–1703.
4. Fukaya C, Otaka T, Obuchi T, et al. Pallidal high-frequency deep brain stimulation for camptocormia: an experience
of three cases. Acta Neurochir Suppl. 2006;99:25–28.

4. TRUNCAL DYSTONIA AND OTHER TRUNCAL DYSKINESIAS
23
5. Yamada K, Goto S, Matsuzaki K, et al. Alleviation of camptocormia by bilateral subthalamic nucleus stimulation in a
patient with Parkinson’s disease. Parkinsonism Relat Disord. 2006;12(6):372–375.
6. Tassorelli C, Furnari A, Buscone S, et al. Pisa syndrome in Parkinson’s disease: clinical, electromyographic, and radio-
logical characterization. Mov Disord. 2012;27(2):227–235.
7. Umemura A, Oka Y, Ohkita K, Yamawaki T, Yamada K. Effect of subthalamic deep brain stimulation on postural ab-
normality in Parkinson disease. J Neurosurg. 2010;112(6):1283–1238.
8. Bonanni L, Thomas A, Varanese S, Scorrano V, Onofrj M. Botulinum toxin treatment of lateral axial dystonia in
Parkinsonism. Mov Disord. 2007;22(14):2097–2103.
9. Azher SN, Jankovic J. Camptocormia: pathogenesis, classifi cation, and response to therapy. Neurology.
2005;65(3):355–359.
10. von Coelln R, Raible A, Gasser T, Asmus F. Ultrasound-guided injection of the iliopsoas muscle with botulinum toxin
in camptocormia. Mov Disord. 2008;23(6):889–892.
11. Comella CL, Shannon KM, Jaglin J. Extensor truncal dystonia: successful treatment with botulinum toxin injections.
Mov Disord. 1998;13(3):552–555.

Trunk
Codrin Lungu and Mark Hallett
Cervical dystonia (CD) is the most common form of focal dystonia (1,2). Prevalence
estimates vary widely, given the variability in diagnosis and reporting, but it is thought
that up to 0.4% of the population may be affected (3).
In the majority of cases, CD is a primary focal dystonia, or part of a primary regional
or generalized dystonia. Secondary CD has been described, and association with exter-
nal trauma deserves mention, although this is a controversial subject (4,5).
Clinical evaluation of CD relies on semiquantitative clinical rating scales. The Burke-
Fahn-Marsden (BFM) scale (6) has been in use since the 1980s in clinical and research
contexts, but is limited for focal dystonia use, given that only a small part of the score is
dedicated to each focal component. The Toronto Western Spasmodic Torticollis Rating
Scale (TWSTRS) (7), which includes a severity component (exam-based) and disability
and pain components (historic information), is currently the most widely used for CD
evaluation (8). The evaluation also takes into account the presence or absence of a “geste
antagoniste,” where regional sensory stimulation can improve the abnormal posture.
Pathophysiologically, it is associated with abnormal excitability and connectivity at
the brainstem, basal ganglia, and cortical levels (9–11). This is expressed at muscular
level by abnormal activation and cocontraction of agonist and antagonist muscle groups
(12), resulting in abnormal postures, limitations in movement range, and occasionally
dystonic tremor.
Botulinum neurotoxin (BoNT) is the most effective therapy modality for CD (13,14),
as demonstrated by multiple clinical trials (15). BoNT can maintain treatment effi cacy
for as long as 20 years (16), is overall safe and well tolerated, and is currently offered
as fi rst line therapy for CD. Deep brain stimulation surgery, targeting the GPi portion
of the pallidum, has also shown effi cacy, albeit with less predictable effects and higher
risk of side effects (17,18). It is, however, a good option for patients who do not respond
adequately to BoNT or develop immunoresistance (13,19). Oral medications have a lim-
ited role at best. Physical therapy can be used to supplement BoNT injections with var-
iable results.
Injection technique and muscle targeting will depend on clinical presentation and
primary abnormal posture or movement. Devising a treatment plan starts with exami-
nation of the patient at rest, while allowing the abnormal postures to develop unim-
peded (20). The primary abnormal movements are then identifi ed and classifi ed into
rotational displacement (torticollis), with the primary direction described by the side
of the midline to which the chin deviates; lateral displacement (laterocollis), anterior or
posterior deviation (anterocollis and retrocollis respectively); shoulder elevation; sagit-
tal or lateral shift. Presence or absence of dystonic tremor is also noted. It is important
to differentiate primary deviation from compensatory antagonistic activity given that,
5
Cervical Dystonia

5. CERVICAL DYSTONIA
25
in practice, antagonist muscles can occasionally appear more active and hypertrophied
than the primary dystonic muscles.
In addition to clinical evaluation, many centers, ours included, use electromyography
(EMG) for initial evaluation of the dystonic muscles, which can help clarify patterns
of dystonic activity and guide the initial treatment plan (12,21). EMG is often further
used to aid in muscle identifi cation and targeting, with small but signifi cant benefi t on
effi cacy (22). Ultrasound (US) is very valuable in providing accurate localization, but no
large studies exist addressing the overall outcome when using one technique over the
other.
The choice of muscles targeted depends on the primary dystonic deviation
For rotational displacement, the main effectors are the ipsilateral splenius capitis (the
•
strongest muscle involved in this movement) and the contralateral sternocleidomas-
toid, with secondary contributions from the longissimus capitis
For laterocollis, the main effector is the ipsilateral levator scapulae with secondary
•
contribution from the ipsilateral splenius capitis
For retrocollis, the main muscles involved are the bilateral cervical longitudinal
•
paraspinal muscles and bilateral splenius capitis
For anterocollis, the muscles involved are bilateral sternocleidomastoids, scalene
•
complexes, and anterior paravertebral muscles
Shoulder elevation involves primarily the ipsilateral trapezius with secondary con-
•
tribution from the ipsilateral levator scapulae
Dystonic tremor characteristically involves bilateral longitudinal paraspinals, sple-
•
nius capitis, and possibly sternocleidomastoid (SCM) muscles
The total dose utilized will vary by serotype, severity, and specifi cs of each case (23).
Few examples of standard starting doses for various formulations are given below.
The total dose demonstrating effi cacy for onabotulinumtoxinA in clinical trials varied
from 100 to 300 Units. In de novo patients, starting doses of 140 to 165 Units have been
used (24). For abobotulinumtoxinA, a starting dose of 500 Units has shown effi cacy and
is commonly employed (25,26). In initial trials, rimabotulinumtoxinB doses of 2,500 to
10,000 Units have been found to be effective, but in practice doses up to 20,000 Units are
safely administered (27,28). After initiation of therapy, the dose can be modifi ed and, if
needed, increased in subsequent sessions.
Some guidelines for BoNT dosing for individual muscles have been published,
addressing the various formulations (25,29). For the sternocleidomastoid, a dose of 20
Units of the onabotulinumtoxinA formulation or 100 Units of the abobotulinumtoxinA
formulation appears to suffi ce (30), and much higher doses should be avoided given the
risk of dysphagia associated with SCM injections. When using the onabotulinumtoxinA
formulation, we commonly inject 50 to 150 Units in the splenius capitis, 25 to 100 Units
in the levator scapulae, 50 to 100 Units in the trapezius, 10 to 30 Units in the longitudi-
nal paraspinals. For each muscle, the injection targets the bulk of the muscle mass or,
if present, areas of tenderness or hypertrophy, while avoiding vascular and nervous
structures. Muscles are identifi ed based on knowledge of the local anatomy aided by
EMG and/or ultrasound guidance. It is good practice to stabilize the muscle between

ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES
26
the fi ngers of the noninjecting hand and perform the injection to a depth that varies
based on anatomy and individual patient constitution (20). The dose is delivered in one
injection site or divided into multiple sites based on muscle size and the volume needed
to achieve the desired dose. For example, we and others prefer to inject no more than
~ 0.25 mL per site in the SCM, and ~ 0.5 mL per site in the splenius.
Peak benefi t from BoNT injections in CD is typically seen at 4 to 8 weeks after injec-
tion (24,28), with a magnitude of benefi t in the 20% to 30% range when expressed by
improvement in CD rating scales, and an average duration of benefi t of approximately
3 months (23,31). The most common side effects are weakness, dysphagia (particularly
with SCM injections; targeting the upper portion of the muscle and limiting the dose
and volume injected reduce the risk), and pain (29,31). The BoNT type B toxin has a
particular tendency to cause dry mouth (28).
REFERENCES
1. Fahn S. The varied clinical expressions of dystonia. Neurol Clin. 1984;2(3):541–554.
2. Stacy M. Epidemiology, clinical presentation, and diagnosis of cervical dystonia. Neurol Clin. 2008;26(suppl 1):23–42.
3. Jankovic J, Tsui J, Bergeron C. Prevalence of cervical dystonia and spasmodic torticollis in the United States general
population. Parkinsonism Relat Disord. 2007;13(7):411–416.
4. Fletcher NA, Harding AE, Marsden CD. The relationship between trauma and idiopathic torsion dystonia. J Neurol
Neurosurg Psychiatry. 1991;54(8):713–717.
5. Sheehy MP, Marsden CD. Trauma and pain in spasmodic torticollis. Lancet. 1980;1(8171):777–778.
6. Burke RE, Fahn S, Marsden CD, Bressman SB, Moskowitz C, Friedman J. Validity and reliability of a rating scale for
the primary torsion dystonias. Neurology. 1985;35(1):73–77.
7. Consky E BA, Belle L, Ranawaya R, Lang AE. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): as-
sessment of validity and inter-rater reliability. Neurology. 1990;40(suppl 1):445.
8. Comella CL, Stebbins GT, Goetz CG, Chmura TA, Bressman SB, Lang AE. Teaching tape for the motor section of the
Toronto Western Spasmodic Torticollis Scale. Mov Disord. 1997;12(4):570–575.
9. Blood AJ, Kuster JK, Woodman SC, et al. Evidence for altered basal ganglia-brainstem connections in cervical dysto-
nia. PLoS One. 2012;7(2):e31654.
10. Singer C, Velickovic M. Cervical dystonia: etiology and pathophysiology. Neurol Clin. 2008;26(suppl 1):9–22.
11. Tolosa ES Marti MJ. Adult-onset idiopathic torsion dystonias. In: Watts RL Koller WC, eds. Movement Disorders
Neurologic Principles and Practice. 2nd ed. New York, NY: McGraw-Hill; 2004:511–526.
12. Deuschl G, Heinen F, Kleedorfer B, Wagner M, Lucking CH, Poewe W. Clinical and polymyographic investigation of
spasmodic torticollis. J Neurol. 1992;239(1):9–15.
13. Albanese A, Asmus F, Bhatia KP, et al. EFNS guidelines on diagnosis and treatment of primary dystonias. Eur J Neurol.
2011;18(1):5–18.
14. Simpson DM, Blitzer A, Brashear A, et al. Assessment: botulinum neurotoxin for the treatment of movement disorders
(an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American
Academy of Neurology. Neurology. [Meta-Analysis]. 2008;70(19):1699–1706.
15. Colosimo C, Tiple D, Berardelli A. Effi cacy and safety of long-term botulinum toxin treatment in craniocervical dysto-
nia: a systematic review. Neurotox Res. [published online ahead of print February 23, 2012].
16. Mejia NI, Vuong KD, Jankovic J. Long-term botulinum toxin effi cacy, safety, and immunogenicity. Mov Disord.
2005;20(5):592–597.
17. Ostrem JL, Starr PA. Treatment of dystonia with deep brain stimulation. Neurotherapeutics. 2008;5(2):320–330.
18. Pretto TE, Dalvi A, Kang UJ, Penn RD. A prospective blinded evaluation of deep brain stimulation for the treatment
of secondary dystonia and primary torticollis syndromes. J Neurosurg. 2008;109(3):405–409.
19. Kiss ZH, Doig-Beyaert K, Eliasziw M, Tsui J, Haffenden A, Suchowersky O. The Canadian multicentre study of deep
brain stimulation for cervical dystonia. Brain. 2007;130(Pt 11):2879–2886.
20. Anderson TJ, Rivest J, Stell R, et al. Botulinum toxin treatment of spasmodic torticollis. J R Soc Med.
1992;85(9):524–529.
21. Van Gerpen JA, Matsumoto JY, Ahlskog JE, Maraganore DM, McManis PG. Utility of an EMG mapping study in treat-
ing cervical dystonia. Muscle Nerve. 2000;23(11):1752–1756.

5. CERVICAL DYSTONIA
27
22. Comella CL, Buchman AS, Tanner CM, Brown-Toms NC, Goetz CG. Botulinum toxin injection for spasmodic torticol-
lis: increased magnitude of benefi t with electromyographic assistance. Neurology. 1992;42(4):878–882.
23. Comella CL, Thompson PD. Treatment of cervical dystonia with botulinum toxins. Eur J Neurol. 2006;13(suppl
1):16–20.
24. Greene P, Kang U, Fahn S, Brin M, Moskowitz C, Flaster E. Double-blind, placebo-controlled trial of botulinum toxin
injections for the treatment of spasmodic torticollis. Neurology. 1990;40(8):1213–1218.
25. Hefter H, Kupsch A, Mungersdorf M, Paus S, Stenner A, Jost W. A botulinum toxin A treatment algorithm for de novo
management of torticollis and laterocollis. BMJ Open. 2011;1(2):e000196.
26. Wissel J, Kanovsky P, Ruzicka E, et al. Effi cacy and safety of a standardised 500 Unit dose of Dysport (clostridium bot-
ulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective,
multicentre, randomised, double-blind, placebo-controlled, parallel group study. J Neurol. 2001;248(12):1073–1078.
27. Berman B, Seeberger L, Kumar R. Long-term safety, effi cacy, dosing, and development of resistance with botulinum
toxin type B in cervical dystonia. Mov Disord. 2005;20(2):233–237.
28. Brashear A, Lew MF, Dykstra DD, et al. Safety and effi cacy of NeuroBloc (botulinum toxin type B) in type A-responsive
cervical dystonia. Neurology. 1999;53(7):1439–1446.
29. Novak I, Campbell L, Boyce M, Fung VS. Botulinum toxin assessment, intervention and aftercare for cervical dystonia
and other causes of hypertonia of the neck: international consensus statement. Eur J Neurol. 2010;17(suppl 2):94–108.
30. Dressler D. Electromyographic evaluation of cervical dystonia for planning of botulinum toxin therapy. Eur J Neurol.
2000;7(6):713–718.
31. Poewe W, Schelosky L, Kleedorfer B, Heinen F, Wagner M, Deuschl G. Treatment of spasmodic torticollis with local
injections of botulinum toxin. One-year follow-up in 37 patients. J Neurol. 1992;239(1):21–25.

Trunk
Codrin Lungu and Mark Hallett
Hemifacial spasm (HFS) is the best known example of a peripherally-induced move-
ment disorder. It manifests as involuntary, intermittent, irregular tonic-clonic synchro-
nous contractions of the muscles innervated by cranial nerve VII on one side of the face
(1). It can be bilateral, but then the movements are asynchronous on the two sides of
the face.
HFS is a sporadic condition with adult onset, although rare familial cases have been
described. Prevalence estimates vary from 7 to 15 per 10,000 (2,3), and the condition is
much more common in Asian populations (4). By far, the most common etiology is a
vascular compression of the facial nerve (5), with other possible causes involving vari-
ous compressive or displacing processes, including tumors (6,7).
Pathophysiologically, one theory asserts that the area of demyelination at the site of
compression is the origin of abnormal discharges and the pathologic manifestations (8).
Ectopic discharges occur at sites of demyelination, and lateral spread occurs between
adjacent demyelinated nerves (ephaptic transmission), which explains the synchronous
involvement of the entire face. This improves after surgical decompression of the nerve
(9). Another theory is that the nerve compression causes secondary hyperexcitability of
the facial nerve nucleus.
Oral treatment is of limited value, and agents tried with variable and small success
included carbamazepine, baclofen, clonazepam, anticholinergics, antipsychotics, gaba-
pentin, and levetiracetam (7,10).
Botulinum neurotoxin (BoNT) focal injection is the treatment of choice for most
patients. It has shown very good effi cacy, with up to 95% improvement in severity, and
with repeated injections the benefi t is usually maintained for many years (11,12). The
duration of action is similar to other indications, around 3 months. The actual targeted
sites of injection depend on the distribution of the spasm, but in most patients it appears
that targeting the periocular region (orbicularis oculi) is most effective, and sometimes
diffuse HFS is symptomatically controlled with only orbicularis oculi injections. We
use a similar pattern of injection in the orbicularis muscle as used for blepharospasm.
Injections are made away from the midline on the upper eyelid to avoid the levator and
away from the medial aspect of the lower lid to avoid loss of control of tears (13). In our
practice, the next most common injections beyond the eye area are in the zygomaticus
or risorius when lateral and upward movement of the corner of the mouth is promi-
nent. However, it is necessary to be very cautious when injecting these muscles because
excessive weakness will lead to an asymmetrical smile, a bad cosmetic result, and the
toxin can diffuse into the buccinators muscles resulting in involuntary cheek biting. The
typical dose using onabotulinumtoxinA varies between 30 and 40 Units (14), but in our
practice we usually begin with a lower dose, targeting only the orbicularis oculi.
6
Hemifacial Spasm

6. HEMIFACIAL SPASM
29
Surgical treatment, consisting of vascular decompression, is used either as an addi-
tional option for patients who do not obtain the expected results with BoNT, or as an
initial approach, depending on the circumstances, patient preferences, availability of
an experienced surgical center, and identifi cation of a clear anatomic abnormality on
imaging. With well-selected patients, a cure rate of 90% to 95% can be obtained, but
hearing loss or facial palsy, which can be permanent, can occur in approximately 1%
of cases (15,16).
REFERENCES
1. Wang A, Jankovic J. Hemifacial spasm: clinical fi ndings and treatment. Muscle Nerve. 1998;21(12):1740–1747.
2. Auger RG, Whisnant JP. Hemifacial spasm in Rochester and Olmsted County, Minnesota, 1960 to 1984. Arch Neurol.
1990;47(11):1233–1234.
3. Nilsen B, Le KD, Dietrichs E. Prevalence of hemifacial spasm in Oslo, Norway. Neurology. 2004;63(8):1532–1533.
4. Wu Y, Davidson AL, Pan T, Jankovic J. Asian over-representation among patients with hemifacial spasm compared to
patients with cranial-cervical dystonia. J Neurol Sci. 2010;298(1–2):61–63.
5. Tan EK, Chan LL. Clinico-radiologic correlation in unilateral and bilateral hemifacial spasm. J Neurol Sci.
2004;222(1–2):59–64.
6. Digre K, Corbett JJ. Hemifacial spasm: differential diagnosis, mechanism, and treatment. Adv Neurol.
1988;49:151–176.
7. Esper CD Aia PG, Cloud LJ, Factor SA. Cramps and spasms. In: Hallett M, Poewe W, eds. Therapeutics of Parkinson’s
Disease and Other Movement Disorders. Chichester, UK: Wiley Blackwell; 2008:363–370.
8. Nielsen VK. Electrophysiology of the facial nerve in hemifacial spasm: ectopic/ephaptic excitation. Muscle Nerve.
1985;8(7):545–555.
9. Nielsen VK, Jannetta PJ. Pathophysiology of hemifacial spasm: III. Effects of facial nerve decompression. Neurology.
1984;34(7):891–897.
10. Daniele O, Caravaglios G, Marchini C, Mucchiut L, Capus P, Natale E. Gabapentin in the treatment of hemifacial
spasm. Acta Neurol Scand. 2001;104(2):110–112.
11. Bentivoglio AR, Fasano A, Ialongo T, Soleti F, Lo Fermo S, Albanese A. Outcome predictors, effi cacy and safety of
Botox and Dysport in the long-term treatment of hemifacial spasm. Eur J Neurol. 2009;16(3):392–398.
12. Simpson DM, Blitzer A, Brashear A, et al. Assessment: botulinum neurotoxin for the treatment of movement disorders
(an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American
Academy of Neurology. Neurology. [Meta-Analysis]. 2008;70(19):1699–1706.
13. Lungu C, Hallett M. Other jerks and startles. In: Jankovic J, Alberta A eds. Hyperkinetic Movement Disorders: Differential
Diagnosis and Treatment. Oxford, UK: Wiley-Blackwell; 2012:236–256.
14. Gill HS, Kraft SP. Long-term effi cacy of botulinum a toxin for blepharospasm and hemifacial spasm. Can J Neurol Sci.
2010;37(5):631–636.
15. Hyun SJ, Kong DS, Park K. Microvascular decompression for treating hemifacial spasm: lessons learned from a pro-
spective study of 1,174 operations. Neurosurg Rev. 2010;33(3):325–334; discussion 34.
16. Samii M, Gunther T, Iaconetta G, Muehling M, Vorkapic P, Samii A. Microvascular decompression to treat hemifacial
spasm: long-term results for a consecutive series of 143 patients. Neurosurgery. 2002;50(4):712–718; discussion 8–9.

Trunk
Katharine E. Alter and Fatta B. Nahab
Patients presenting with lower extremity hypertonia, including dystonia are fre-
quently referred to physicians for evaluation and or intervention. Determining the
cause of the patient’s symptoms is required before proceeding to treatment because
some disorders can be directly treated while only symptomatic management is pos-
sible in others. The etiology of lower limb dystonia (LLD) includes a diverse group
of disorders including idiopathic or primary dystonia, secondary dystonia, as well as
psychogenic causes. Primary dystonias include focal or task-specifi c dystonia, vari-
ous genetic and inherited dystonias, and paroxysmal disorders. Secondary dystonia
may be clinically differentiated from primary dystonia in that symptoms may not
resolve with sleep and are frequently caused by an upper motor neuron lesion or
neurodegenerative process. Secondary dystonia may also result from trauma, toxic
exposures, medication-related side effects, and from metabolic conditions such as
Wilson’s disease (1–4).
Dystonia of the lower limbs occurs commonly in patients with secondary causes of
dystonia. It is also a presenting symptom in patients presenting with childhood onset
primary dystonia, particularly DYT1 and DYT5 (Dopa Responsive Dystonia). This is
in stark contrast to idiopathic or focal dystonia, where dystonia confi ned to the lower
limb at presentation is unusual and warrants careful evaluation. The differential diag-
nosis for patients presenting with adult onset idiopathic LLD is quite diverse, as noted
above (1,2).
This chapter will provide a brief review of common causes and patterns seen in
patients with LLD. Many of these patients present with signifi cant functional limita-
tions due to involuntary muscle activity and abnormal postures caused by dystonia and
may benefi t from a variety of interventions, including botulinum toxin (BoNT) injection,
oral medications, physical and occupational therapy, splinting and modalities such as
electrical stimulation. The reader is referred to several excellent texts and reviews for a
detailed discussion of idiopathic and secondary dystonia assessment, work up, and the
role of medical and surgical interventions for LLD (1,5–10).
CHARACTERISTICS OF DYSTONIA
Dystonia is a movement disorder characterized by involuntary movements includ-
ing sustained or intermittent postures. These postures are often repetitive and have
a twisting quality. Other common features include cocontraction of agonist/antago-
nist muscle pairs and overfl ow to adjacent or contralateral muscles/sites. Individual
7
Lower Limb Dystonia

7. LOWER LIMB DYSTONIA
31
patients may present with postures which are hyperkinetic (e.g., tremor) while oth-
ers present with postures that appear more fi xed or hypokinetic. These involuntary
movements often worsen with stress, attempts at voluntary muscle recruitment, talk-
ing, and so on (10–12).
PHYSICIAN PRACTICE PATTERNS AND LOWER LIMB DYSTONIA
A physician’s training, experience, practice patterns, and referral base all infl uence the
clinical problems and diagnoses (including dystonia) for which patients are referred for
evaluation and treatment. For a movement disorder trained neurologist, the most com-
mon cause of LLD may be idiopathic or primary dystonia. General neurologists or phy-
siatrists more commonly encounter patients with limb dystonia secondary to trauma,
upper motor neuron injury syndromes as seen in patients with cerebral palsy (CP) or
following stroke or traumatic brain injury (TBI) (4,5,7–9).
McKeon et al. in a 2008 retrospective review, reported the various diagnoses of
patients who presented with LLD to a movement disorders clinic during the 10-year
review period. Of the 36 patients identifi ed with dystonia, 86% of the patients were
female, the mean age was 47.6 years, duration of symptoms 28.8 months, and mean
follow 3.1 years (range 0.2–10.5 years). Nineteen of 36 patients presented with idio-
pathic dystonia, with action induced or task-specifi c dystonia being the most com-
mon type. Ten of the 36 patients presented with posttraumatic dystonia, which more
often than not presented as dystonia at rest and was described as static. Other diagno-
ses included dystonia related to Parkinson disease, complex regional pain syndrome
(CRPS), psychogenic dystonia, stiff person syndrome, stroke and idiopathic dystonia
associated with spasticity. The authors reported widely varied clinical presentations
including fi xed inversion of the foot in posttraumatic dystonia and various postures
and provoking tasks for patients with action-induced dystonia. The authors recom-
mended imaging for all patients presenting with dystonia confi ned to a lower limb and
a trial of levodopa for patients presenting with isolated LLD in order to exclude dopa-
responsive dystonia (DYT5) (13).
PATTERNS OF INVOLVEMENT
The patient’s history, physical examination, and the distribution and pattern of involve-
ment all provide clues to the etiology of the patient’s dystonia as well as directing fur-
ther work up. A detailed history including age and symptoms at presentation, duration,
spread or generalization of the dystonia, provoking maneuvers, the presence or absence
of a sensory trick, toxic/occupational exposures, and medication history should all be
documented. A detailed family history should be obtained to guide the evaluation of
potential inherited causes of LLD (1–3, 10).
Dystonia is characterized by its anatomical distribution including focal, segmen-
tal, regional, or generalized patterns of involvement. In patients presenting with focal

ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES
32
dystonia, a single muscle or several muscles in a single limb segment are affected.
Segmental dystonia commonly affect muscles in at least two adjacent areas of the body,
such as the neck and upper arm. Generalized dystonia affects multiple muscles in a
more widespread distribution. Segmental and generalized dystonia are more com-
monly seen in patients with secondary dystonia and some forms of inherited dystonia
such as DYT1 as well as in paroxysmal disorders. Common causes of secondary dys-
tonia include stroke, CP, TBI, Parkinson disease, corticobasal degeneration, metabolic
conditions (e.g., Wilson’s disease), and posttraumatic dystonia. Patients with segmental
or generalized dystonia may also present with a focal problem such as a striatal or hitch-
hiker toe or fl exed toe (14–18).
PATIENT EVALUATION
The literature is universal in reporting that dystonia confi ned to the lower limb at pre-
sentation is unusual in adult onset idiopathic dystonia LLD (12,18). Neuroimaging,
electrodiagnostic testing, and laboratory studies to exclude neuroacanthocytosis, infl am-
matory causes metabolic defects, and impaired copper metabolism are recommended
for patients presenting with isolated LLD. This is to rule out potentially treatable or
reversible causes of dystonia including spinal stenosis, structural lesions, tumors, auto-
immune and heredodegenerative disorders. Despite extensive investigation, the neu-
roanatomical site or sites of dysfunction in patients with primary LLD dystonia have
yet to be determined. Neuroimaging in patients with primary dystonia is most often
normal using standard clinical imaging methods. A number of potential sites have been
proposed including the striatum (putamen), cerebellum, thalamus, and somatosensory
cortex. A number of abnormalities have been identifi ed on neurophysiologic evaluations
including changes in somatosensory function and cortical representation. In patients
presenting with secondary dystonia, imaging studies may reveal focal or larger lesions
at nearly any level of the central nervous system (CNS). As noted above, a detailed
medication history may reveal risks for dystonia related to toxic exposure or suggest a
diagnosis of tardive dyskinesia.
Neuroanatomical or neurophysiologic correlates may contribute to differences in the
patterns that are seen in patients with idiopathic versus secondary causes of dystonia.
For example, LLD as previously noted is much more common in patients with second-
ary dystonia than in patients with idiopathic dystonia. Dystonia is also more common in
females from idiopathic and secondary etiologies suggesting a predisposition for dys-
tonia in females (19–21).
IDIOPATHIC DYSTONIA
In contrast to dystonia involving cervical, oromandibular, or upper limb muscles,
idiopathic dystonia limited to lower limb muscles at presentation is relatively rare.
The incidence of idiopathic LLD is reported to be 0.7% to 1.7% of all patients pre-
senting with idiopathic dystonia. Two age peaks are reported to exist for patients
presenting with LLD including an early peak in the fi rst 2 decades and a second
peak after age 40 (22,23). The age at presentation for LLD in the older group may be
slightly younger than for patients presenting with cervical or oromandibular idio-
pathic dystonia (24).

7. LOWER LIMB DYSTONIA
33
FOCAL OR TASK-SPECIFIC DYSTONIA OF THE LOWER LIMBS
In contrast to focal dystonia presenting in cervical, oromandibular or upper limb mus-
cles, task-specifi c or occupational dystonia involving the lower limb is uncommon
(13,25). There have been case reports of focal LLD involving long distance, high mileage
runners, drummers, tradesmen, cyclists, dancers, and knife sharpeners (26–30).
Neuroimaging is typically normal as noted above, but should be performed to
exclude potentially treatable causes of dystonia. Focal dystonia in the lower limb is also
reported to generalize more often than focal dystonia presenting in the upper limb (26).
The pattern of involvement for individual patients, particularly runners, is variable.
Commonly involved muscles include distal muscles, including the plantar fl exors, fore-
foot supinators, and toe fl exors. Proximal muscle involvement may include hip fl exion,
extension adduction, knee fl exion or extension. Patient assessment should include tasks
that assess specifi city of the dystonia, for example if running provokes the patient’s
symptoms, then the patients should also be asked to walk. Specifi city can also be elic-
ited by having the patient walk backwards or walk/run on a treadmill. The presence of
a sensory trick or geste antagoniste by history is commonly reported by patients with
focal dystonia. Over time the pattern of dystonia may evolve or spread to other tasks or
nearby muscles, though generalization is unlikely.
NONFOCAL LOWER LIMB DYSTONIA
In patients with adult onset idiopathic dystonia, segmental or generalized dystonia
confi ned to a lower limb is also atypical and therefore requires a detailed work up as
described above (1,2,9,31).
The diverse differential diagnosis of idiopathic dystonia presenting in lower limb
includes DYT5, tyrosine hydroxylase defi ciency, pantothenate kinase-associated neuro-
degeneration (PKAN), and other hereditary primary dystonias (32). Lower limb involve-
ment is also seen in patients with Wilson’s disease. LLD as a presenting symptom may
also be seen in patients who are eventually diagnosed with Parkinson disease (33).
In some patients with idiopathic segmental or generalized dystonia, symptoms will
begin focally but eventually spread to involve other areas including the upper limb. This
somatotropic spread of dystonia is reported to be more rapid in the younger age group
of patients with LLD than in the older age group. LLD is often provoked by voluntary
activation in both idiopathic dystonia and in patients with upper motor neuron (UMN)
(22). Fixed postures that do not vary with activity are more common in posttraumatic
causes of dystonia (CRD) (22,23).
Common clinical patterns in patients presenting with segmental or generalized dys-
tonia include fl exor or extensor patterns of distal and proximal muscles with multiple
muscles and limb segments involved. Patients with segmental and generalized dystonia
are generally treated with systemic medications or other treatments. These patients may
benefi t from BoNT injections, to address specifi c issues or a focal portion of the dys-
tonic posture, for example, foot equines or great toe extension preventing heel strike or
shoe wear. A specifi c goal should be identifi ed in these patients given dose limits with
neurotoxins and the fact that multiple muscles are often involved. Combined therapy
with neurotoxins and oral medications, intrathecal baclofen therapy, and deep brain
stimulation (DBS) may also provide signifi cant benefi ts to patients with segmental or
generalized idiopathic dystonia.

ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES
34
SECONDARY DYSTONIA
Patterns of muscle involvement and neurotoxin therapy for upper motor neuron syn-
dromes are covered in detail elsewhere in this text. Patients with secondary dystonia
from other causes including Parkinson disease and corticobasal degeneration may also
benefi t from neurotoxin therapy. As with patients presenting with idiopathic segmental
or generalized dystonia, multiple muscles are often involved. Therefore, a specifi c goal
for neurotoxin therapy should be identifi ed prior to proceeding to treatment. Combined
therapy with neurotoxins and oral medications, intrathecal baclofen therapy, and DBS
may also provide signifi cant benefi ts to patients with generalized secondary dystonia
(5,6,8,9,12,13,15).
SUMMARY
LLD is a complex problem resulting from a diverse group of disorders with varied clin-
ical presentations and symptoms. A detailed patient examination and functional assess-
ment should direct treatment planning and selection. Patients presenting with LLD may
benefi t from a variety of therapies including rehabilitation therapies, orthotics, focal and
systemic agents/medications, and surgical treatments. In patients who are referred for
neurotoxin therapy this assessment will also guide muscle selection and injection pat-
terns (5,34–36).
REFERENCES
1. Fahn S, Jankovic J, Hallett M, Jenner P. Dystonia—phenomenology, classifi cation, etiology, pathology, biochemistry,
and genetics. In: Fahn S, Jankovic J, Hallett M, Jenner P eds. Principles and Practices of Movement Disorders. Philadelphia,
PA: Elsevier; 2007:307–343.
2. Schneider SA, Edwards MJ, Grill SE, et al. Adult onset primary lower limb dystonia Mov Disord. 2006;11:767–771.
3. Defazio G. The epidemiology of primary dystonia: current evidence and perspectives. Eur J Neuro. 2010;17(supp
1):9–14.
4. Espay AJ, Lan AE. The psychogenic toe signs. Neurology. 2011;77:508–509.
5. Elovic EP, Esquenazi AP, Alter KE, et al. Chemodenervation and nerve blocks in the diagnosis and management of
spasticity and muscle over activity. PM R. 2009;1(9):842–851.
6. Gracies JM, Bayle N, Vinti M, et al. Five step clinical assessment in spastic paresis. Eur J Phys Rehabil Med.
2010;46:411–423.
7. Gracies JM. Physiologic effects of botulinum toxin in spasticity Mov Disord. 2004;19(suppl 8):S120-S128.
8. Gracies JM. Traditional pharmacological treatments for spasticity. Part 1: local treatments. Muscle Nerve Suppl.
1997;6:S61-S91.
9. Gracies JM Traditional pharmacological treatments for spasticity. Part II: general and regional treatment. Muscle Nerve
Suppl. 1997;6:S92-S120.
10. Treatment of Dystonia In: Marsden CD, Fahn S, eds. Movement Disorders, Philadelphia, PA: Elsevier; 1987: 345–367.
11.
Sanger TD, Chen D, Fehlings DL, et al. Defi nition and classifi cation of hyperkinetic movements in childhood. Mov
Disord. 2010;25(11):1538–1549.
12. Strager S, Rodnitzky RL, Gonzalez-Allegre P. Secondary dystonia in a botulinum toxin clinic: clinical characteristics
neuroanatomical substrate and comparison with idiopathic dystonia. Parkinsonism Relat Disord. 2011;17:749–752.
13. Mckeon A, Matsumoto JY, Bower JH, et al. The spectrum of disorders presenting as adult onset focal lower extremity
dystonia. Parkinsonism Relat Disord. 2008;14:613–619.
14. Lo SE, Frucht SJ. Is focal task-specifi c dystonia limited to the hand and face. Mov Disord. 2007;22:1009–1011.
15. Braber TA, Basu B, Shakespeare D, et al. Botulinum toxin in the management of hitchhiker’s toe. Neuro Rehab.
2011;28(4):395–399.

7. LOWER LIMB DYSTONIA
35
16. Jankovic J, van der Linden C. Dystonia and tremor induced by peripheral trauma: predisposing factors. J Neurol
Neurosurg Psychiatry. 1988;51(12):1512–1519.
17. Fletcher NA, Harding AE, Marsden CD. The relationship between trauma and idiopathic torsion dystonia. J Neurol
Neruosurg Pyschiatry. 1991;54(8):713–717.
18. Verdugo RJ, Ochoa JL. Abnormal movements in coplex regional pain syndrome: assessment of their nature. Muscle
Nerve. 2000;23(2):198–205.
19. Martino D, Macerello A, Abbruzzese G, et al. Lower limb involvement in adult onset primary dystonia: frequency and
clinical features Eur J Neurol. 2010;17:242–246.
20. Brin MF, Comella CL. Pathophysiology of dystonia. In: Brin MF, Comell CL, Jankovic J, eds. Dystonia: Etiology, Clinical
Features and Treatment. Philadelphia, PA. Lippincott Williams Wilkins; 2004:5–10.
21. Defazio G, Abbruzzese G, Girlanda P, et al. Phenotypic overlap in familial and sporadic primary adult onset extracra-
nial dystonia. J Neurol. 2012;10(5):6514–6516.
22. Martino D. Lower limb involvement in adult onset primary dystonia: frequency and clinical features. Eur J Neurol.
2010;17:242–246.
23. O’Riordan S, Raymond D, Lynch T, et al. Age at on set as a factor in determining the phenotype of primary torsion
dystonia. Neurology. 2004;63:1423–1426.
24. Schneider SA, Edwards MJ, Quinn NP, Bhatia KP. Adult-onset primary lower limb dystonia: clinical description of a
rare entity. Mov Disord. 2005;20(suppl 10):S24.
25. Pont-Sunyer C, Marti MJ, Tolosa E. Focal limb dystonia. Eur J Neurol. 2010;17(suppl 1):22–27.
26. Leveille LA, Clement DB. Case report; action induced focal dystonia in long distance runners. Clin J Sport Med.
2008;18(5):467–468.
27. Wu LJ, Jankovic J. Runner’s dystonia. J Neurol Sci. 2006;251(1–2):73–76.
28. McClinton S, Heiderscheit B. Diagnosis of primary task specifi c lower extremity dystonia in a runner. J Orthop Sports
Phys Ther. 2012;42(8):688–697.
29. Rosset-Llobet JR, Fabregas-Moas S, Pascual-Leone A. Drummer’s lower limb dystonia. Letter to the Editors. J Neurol.
2012;259(6):1236–1237.
30. Garcia-Ruiz PJ, del Var J, Losada M, et al Task specifi c dystonia of the lower limb in a fl amenco dancer. Letter to Editor.
Parkinsonism and Rel Disorders. 2011;17:221–222.
31. Defazio G, Abbruzzese G, Livrea P, et al. Epidemiology of primary dystonia. Lancet Neurol. 2004;3:673–678.
32. Cheyette BNR, Cheyette SNR, Cusmano-Ozag K, et al. Dopa responsive Dystonia presenting as delayed and awkward
gait. Pediatr Neurol. 2008;38(4):273–275.
33. Eggers C, Volk AE, Kahraman D, et al. Are dopa responsive dystonia and Parkinson’s disease related disorders? Letter
to the Editor. Parkinsonism Relat Disord. 2012 Jun;18(5):666–8. {Epub was 2011 Oct 24.}
34. Olver J, Esquenazi VSC, Fung B, et al. Botulinum toxin assessment, intervention and aftercare for lower limb disorders
of movement and muscle tone in adults. Eur J Neurol. 2010;17(suppl 2):57–73.
35. Barrett MJ, Bressman SB, Levy OA, et al. Functional electrical stimulation for the treatment of lower limb dystonia.
Letter to the Editor. Parkinsonism and Rel Disorders. 2012;18(5):660–661.
36. Jankovic J. Treatment of dystonia. Lancet. 2006;5:865–872.

Trunk
Katharine E. Alter and Fatta B. Nahab
The wide range of potential lesions leading to injury of the central nervous system (CNS),
including a constellation of sensorimotor signs or symptoms, is collectively referred to
as the upper motor neuron syndrome (UMNS) (1–3). UMNS-related hypertonia is one
of the most common causes for referral for chemodenervation procedures including
botulinum toxin injections. In adult patients, the most common causes of UMNS are
stroke, traumatic brain injury, and spinal cord injury. In the pediatric population, cere-
bral palsy, resulting from injury to or a lesion in the developing brain, is the most com-
mon cause of UMNS.
UMN SIGNS AND SYMPTOMS
Lance initially described the positive and negative signs associated with UMNS (1).
Negative signs associated with UMNS include weakness, loss of selective motor con-
trol, or dexterity and impaired sensory perception. Positive signs include hyperrefl exia,
pathological refl exes, spasms, and muscle hypertonia (e.g., spasticity, dystonia, rigidity)
Table 8.1 and Figure 8.1 (1–3).
STRETCH REFLEXES AND SPASTICITY
The complex changes in refl ex activity and muscle tone caused by UMN lesions are
not fully understood. What is clear is that changes occur at multiple levels in the CNS
including monosynaptic/polysynaptic pathways at the segmental level and in descend-
ing inhibitory input from higher cortical centers (4–7). Collectively, this resulting loss
of inhibition leads to a net change/increase in alpha motor neuron excitation and the
development of muscle hypertonia (8).
Over 100 years ago, Sherrington fi rst described increased stretch refl exes and extensor
muscle tone in cats following brain transection above the level of the vestibular nuclei
which he termed “decerebrate rigidity” (9). Sherrington also explored the effects of
reduced afferent input on rigidity by severing dorsal nerve roots and noted improve-
ment of “rigidity” (spasticity) (10,11). Since these initial studies, spasticity has been inves-
tigated and further defi ned by a number of eminent neuroscientists including Lance and
others (1–7, 12, 13). Lance described spasticity as a motor disorder characterized by a
“velocity dependent increase in tonic stretch refl exes” (1). Nathan further defi ned spas-
ticity as “a condition in which stretch refl exes that are normally latent become obvious.
Upper Motor Neuron Syndromes
8

8. UPPER MOTOR NEURON SYNDROMES
37
8. UPPER MOTOR NEURON SYNDROMES
37
Table 8.1 Positive and negative signs
Positive
Negative
Spasticity
- Hyperrefl exia
- Spread of stretch refl ex
- Clonus, that is, repetitive refl exes
- Spastic dystonia
Spasms
Disinhibition of fl exor refl exes spasms
- Babinski
- Mass synergy pattern
Loss of dexterity
Slowed movements
Reduced force generation/weakness
Fatigue
Sensory perception disturbances
UMN Injury/Lesion
Positive Signs
Negative Signs
Functional
Impairments
Weakness/Decreased
Force Generation
Loss of Dexterity,
Selective Motor Control
Impaired Sensory
Perception
Acquired Changes:
Rheologic
Biomechanical
Spasticity/hypertonia
Spastic Dystonia
Spasm
Clonus
Disinhibited flexor
responses
Associated reactions
Figure 8.1
Positive and
negative clini-
cal signs.

ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES
38
The tendon refl exes have a lowered threshold to tap, the response of the tapped muscle is
increased, and usually muscles besides the tapped one respond; tonic stretch refl exes are
affected in the same way” (13). While the appearance of UMNS may provide some pro-
tective advantages, the constellation of signs and symptoms also have a negative impact
on a variety of body systems and thereby patient function (14,15).
The location of a CNS lesion has a direct impact on the pattern of refl ex changes that are
observed, particularly when comparing spinal versus cerebral causes of spasticity. Spinal
lesions lead to refl ex changes primarily at a segmental level with changes in polysynaptic
pathways involving inhibitory interneurons (16,17). Herman, in studies of refl ex excitabil-
ity following spinal or cerebral injury, found a slower rise time for refl ex activity in a spinal
model, when compared to the faster rise time for refl ex activity seen in patients with cere-
bral lesions. In spinal spasticity, he postulated that afferent activity from muscle spindles
or fl exor refl ex afferents entered at one spinal level then ascend to involve other levels.
This ascending spread of stimulation leads to muscle responses in limb segments dis-
tant from the original site of afferent stimulation. This phenomenon is clinically observed
when a noxious stimulus at one level, for example the foot, leads to increased tone and/or
spasms in proximal muscles of the knee. This effect is also commonly observed whereby
noxious stimuli from other body systems, that is, a distended bladder, urinary tract infec-
tion, or decubitus ulcer leads to increased tone and spasms at distant sites (16,17).
In cerebral lesions, Herman described a more rapid increase in refl ex activity suggest-
ing monosynaptic pathway changes in muscle spindles and target muscles. He observed
that patients with “cerebral” hypertonia frequently presented with particular patterns
of muscle hyperactivity, such as the fl exed posture seen in post stroke spasticity or the
equinus gait pattern commonly seen in children with cerebral palsy Figures 8.2a, 2b and
8.3 (16,17).
Muscle hypertonia including spasticity, spastic dystonia, dystonia, spasms, and stiff-
ness are all described and are reported to affect quality of life and function in UMNS.
These impairments are, however, only one aspect of the UMNS and may change over
time (17,18).
Figure 8.2 Upper limb pos-
turing, cerebral palsy.

8. UPPER MOTOR NEURON SYNDROMES
39
SECONDARY OR ACQUIRED IMPAIRMENTS ASSOCIATED WITH UMNS
Over time, the changes in muscle activation described above often lead to acquired
or secondary changes in the musculoskeletal system (Table 8.2) (19–23). These effects
include rheologic changes in muscle, and the development of contractures and joint
deformities (Figures 8.2 and 8.4). These secondary impairments are particularly prob-
lematic in children where the combined effects of continuing linear growth are superim-
posed upon UMNS motor impairments and functional limitations (decreased activity,
weight bearing). Even with aggressive management of hypertonia, patients with cere-
bral palsy frequently go on to require surgical interventions for management of these
acquired problems (23,24). One of the many goals of spasticity management for UMN-
related hypertonia, including chemodenervation procedures, is therefore to minimize
the progression of these acquired impairments (24,25).
Collectively, UMNS related impairments may cause limitations in a patient’s qual-
ity of life, passive and active function and/or disabling pain (17–20,24,25). Functional
limitations frequently impact activities of daily living (ADLs), mobility, bowel/bladder
Figure 8.3 Equinus gait,
cerebral palsy.
Table 8.2 Rheologic changes in muscle
Stiffness
Loss of sarcomeres
Fibrosis
Atrophy
Contracture