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Cervical Dystonia
Table 1: Muscles Commonly Affected in Cervical Dystonia, Their
Recently, the Therapeutics and Technology Assessment Subcommittee of
Function, and the Recommended Dose of Botulinum Toxins*
the American Academy of Neurology (AAN) reviewed the literature on BoNT
treatment in CD and identified seven class I (blinded, prospective) studies.
21
Muscle Name Function Dose of Botox (U) Dose of Myobloc (U)
Six of these studies compared BoNTs with placebo and one compared BoNTs
Stenocleodo- 1. Rotation (contra) 40–80 (60) 2,000–3,000
with trihexyphenidyl. The six included one with BoNT-A (Botox), two with
mastoid 2. Tilt (ipsi)
BoNT-A (Dysport), and three with BoNT-B (Myobloc). All six studies depicted
3. Sagittal shift**
4. Antecollis
superiority of BoNTs to placebo in terms of efficacy and safety.
22–27
The
Splenius- 1. Rotation (ipsi) 50–100 2,000–4,000
trihexyphenidyl study
28
was conducted with BoNT-A (Dysport), which was
capitis 2. Tilt (ipsi)
proved to be more efficacious than tirhexyphenidyl in improving motor
3. Sagittal shift***
disability and movements while producing fewer adverse effects. The AAN
4. Retrocollis subcommittee concluded that BoNTs are established as safe and effective
Semi-spinalis 1. Rotation (contra) 20–30 1,000–2,000 for the treatment of CD, and that BoNT injections should be offered as a
capitis 2. Tilt (ipsi)
treatment option to patients with CD (level A). Improvement of pain and
3. Retrocollis
abnormal head and neck postures in these studies ranged from 60 to 95%.
Trapezius 1. Shoulder (elevat) 50–100 2,000–4,000
Comella’s recent review additionally analyzed four double-blind studies that
2. Retrocollis
compared two BoNTs with each other in terms of efficacy, tolerability, and
3. Sagittal shift***
side effects.
29
Of these four studies, two compared BoNT-A (Botox) with
4. Tilt (ipsi)
5. Rotation (assists in
BoNT-A (Dysport),
30,31
one compared Botox with BoNT-A (Xeomin),
32
and one
ipsi and contra)
compared Botox with BoNT-B (Myobloc).
33
One of the two Dysport/Botox
Levator- 1. Shoulder and 20–100 1,000–2,000
studies in CD showed comparable efficacy and side effects when the
scapula scapula (elevat)
investigators used the ratio of three Dysport units to one Botox unit.
30
In
2. Tilt (ipsi) another Dysport/Botox study using two ratios of 3:1 and 4:1, patients who
3. Rotation (contra) received Dysport had more improvement in terms of pain and neck posture,
Scalene 1. Tilt (ipsi) 20–40 1,000–2,000
but showed more side effects.
31
The Xeomin/Botox study
32
showed no
2. Rotation (contra)
difference between the two in terms of improvement of total TWSTRS score
3. Antecollis
and TWSTRS pain score. Both BoNTs displayed the same frequency of side
* Approved in the US; ** Forward; *** Backward.
effects in this study. A ratio of 1:1 was used for this study.
In antecollis a number of other muscles may be involved that are not easily accessible from the
skin surface or via electromyogram. These include: longus colli, longus capitis, rectus capitis,
infrahyoid, and suprahyoid muscles. In some patients, platysma and digastric muscles also
The comparison studies between Botox and Myobloc are more relevant to
contribute to antecollis posture. Antetollis, retrocollis, and sagital shift require bilateral activation.
the practice of BoNT therapy in the US. In a blinded study, Comella et al.
33
doses often produce undesirable side effects (confusion and blurred compared improvement of TWSTRS score at four weeks between 74 and
vision).
14
Clonazepam alone or in combination with botulinum toxins 65 CD patients who received Botox and Myobloc, respectively. There was
(BoNTs) can be helpful by reducing the sharpness of the head jerks in the no significant difference between the two groups with regard to TWSTRS
myoclonic dystonia variant of CD. score. Rates of dysphagia and dry mouth were significantly higher in the
Myobloc group (48 versus 19% and 80 versus 41%, respectively). The
BoNT therapy has changed the life of patients with CD over the past 15 years higher incidence of these adverse effects may be due to the structured
and remains the most effective mode of treatment. BoNTs comprise seven interview adverse effect assessment utilized in the study, and also to the
subtypes, of which only types A and B are in clinical use (type F is effective but fact that all patients were naïve to Myobloc. The duration of Botox action
has a short duration of action). The antidystonic effect of BoNTs is exerted was marginally longer than that of Myobloc (14 versus 12.1 weeks). A
mostly through inhibition of acetylcholine release from pre-synaptic vesicles via recent European double-blind, multicenter study
34
compared Botox with
deactivation of SNARE proteins. For type A, this protein is SNAP 25; for type B Myobloc in naïve patients with CD (55 Botox, 56 Myobloc). The study
it is vesicle-associated membrane protein (VAMP, or synaptobrevin). The showed no significant difference between the two in terms of TWSTRS
analgesic effect of the BoNTs goes beyond this mechanism, taking into account total score or subscores (pain, severity, or disability) at four weeks, or in
a number of other factors, among them inhibition of pain neurotransmitter terms of duration of action. There was also no statistically significant
peptides such as substance P, enkephalin, calcitonin gene-related peptide difference between the two in terms of dysphagia, pain at the site of
(CGRP), and glutamate,
15–17
anti-inflammatory effect,
17
and suppression of injection, and moderate or severe dryness of the mouth. Mild dryness
muscle spindle discharge resulting in reduced excitation of gamma and alpha of the mouth was more common in the Myobloc group.
motor neurons.
18
It has been shown that pain improves sooner and
independently from neck posture in CD after BoNT treatment.
19,20
Emergence of unresponsiveness after chronic use of BoNTs is a treatment
obstacle. A comprehensive review of CD in 1998 cited a figure of 5–10%
Currently, three formulations of BoNT-A are commercially available for for unresponsiveness.
6
Multiple factors could contribute to the clinical
human use: Botox
®
(Allergan, Inc.), Dysport
®
(Ipsen Limited), and Xeomin
®
unresponsiveness, including the development of neutralizing antibodies.
(Merz Pharmceutical). In the US, BoNT-B is distributed iunder the name Although unresponsiveness often relates to the development of neutralizing
Myobloc
®
, and in Europe under the name Neurobloc
®
(Solstice antibodies, some patients continue to respond despite having them. The
Neurosciences, Inc.). In the US, only Botox and Myobloc are approved by the exact correlation between neutralizing antibodies and the clinical
Food and Drug Administration (FDA) and marketed for medical practice. unresponsiveness is not well established or understood at this time.
38 US NEUROLOGY
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