Responsiveness to botulinum toxinum type A in complex regional pain syndrome related fixed dystonia

In patients who have developed dystonia following the onset of complex
regional pain syndrome (CRPS), primary resistance or a decreased response to
botulinum toxin type A (BoNT/A) seems to be a frequent experience of clinicians
who administer BoNT/A. CRPS is usually, although not always, triggered by minor
injury to one limb and the signs reflect the various involvement of mechanisms
that underlie inflammation and vasomotor dysfunction. About 25% of the patients
with CRPS develop fixed dystonia of the affected limb, which can spread to
involve other limbs. This dystonia is distressing and disabling, and its
prognosis is poor. Although, some studies have implicated central nervous
system involvement, our understanding of the mechanisms that underpin fixed
dystonia in CRPS is still very limited. Against this background, the poor or
lack of response of fixed dystonia in CRPS to BoNT/A is intriguing and may
provide additional clues on the pathophysiology of this movement disorder.
However, information on responsiveness to BoNT/A in CRPS related fixed dystonia
is based on individual clinical experiences and has never been formally
studied. Theoretically, the poor or lack of response to BoNT/A may be explained
by technical shortcomings associated with BoNT/A administration or by extrinsic
and intrinsic factors that are related to the disease. To address these
possibilities, this study will assess the responsiveness to a single BoNT/A
administration in CRPS patients with fixed dystonia.

To evaluate the responsiveness of the extensor digitorum brevis (EDB) muscle to
BoNT/A in extremities affected and unaffected by CRPS.

Case-control study

The amplitude of the compound muscle action potential (CMAP) of the EDB muscle
of the affected and unaffected extremity (patients) and left lower extremity
(controls) will be determined pre and post EMG-guided injection of 20 mouse
units (MU) of BoNT/A. In all subjects the presence of antibodies against BoNT/A
will be determined.

Low frequency visit to the hospital (4x 30-45min)
Injection of a small amount of BoNT/A. The possibility that this study leads
to a worsening of complaints in these patients cannot completely be ruled out.
However, for two reasons we dare to state that the risk on eliciting an
exacerbation of the disease by the BoNT/A injections in this study is
negligible. First, we have a broad experience with multiple injections and skin
abrasions from previous studies in this patient group without the occurrence of
unfavorable reactions. Second, in our out-patient clinic many CRPS patients
with dystonia have been injected with BoNT/A without a worsening of complaints.
In addition, in case patients experience a worsening of dystrophic pain there
is the option to treat them with ketamine