There is an ever increasing body of CRPS research which covers
many aspects of this disease. The following is a list of CRPS
studies in 2002-3.
Charles Berde MD PhD
Robert Schwartzman MD
International Dutch RSD Conference: Nov. 14-15,
GENDER DIFFERENCES IN CRPS I/ RSD IN CHILDREN
Charles Berde, M.D., Ph.D., Harvard Medical School, Director, Pain
Treatment Service, Boston Children's Hospital, Boston, Massachusetts
Complex regional pain syndrome, type 1 (CRPS1) or reflex sympathetic
dystrophy (RSD) is being diagnosed more frequently in children and
adolescents. Over the last 12 years, our pain center has examined
the demographics, associated medical and lifestyle factors, and
responses to treatment in over 450 patients. Some demographic features
in children appear different from those described for adults:
(1) Children and adolescents have lower extremity involvement 6
times more often than upper extremity involvement.
(2) Girls are affected roughly 5 times as often as boys.
(3) RSD/CRPS1 is rare below age 8; the incidence increases markedly
just before puberty.
(4) Female dancers, gymnasts and competitive athletes comprise
a high percentage of the patients.
A high percentage of patients present either confined to crutches
or in a wheelchair. School absenteeism is more common in these patients
than in a matched population of rheumatology patients. Coexisting
psychiatric diagnoses commonly include depression, anxiety disorders,
post-traumatic stress disorders, distorted body image and eating
disorders, and stressful family dynamics.
Treatments advocated for RSD have varied largely according to subspecialty
and training of health providers. A program for prospective evaluation
of these patients was established recently with funding from NICHD.
Preliminary studies by Dr. Sethna and others on quantitative sensory
and autonomic evaluation will be summarized. Treatments under prospective
controlled evaluation include physical therapy, cognitive-behavioral
interventions, tricyclics and anticonvulsants, and continuous infusion
RSDS IN CHILDREN AND ADOLESCENTS
(summary of Dr. Berde’s presentation at RSDSA's Tampa
Treatment varies according to the individual child.
It is essential to maintain a close rapport with the patient and
family so that they can understand and cope with the treatment.
Active PT and CBT (cogntive behaviour therapy) are at the top of
the list for treatment and a large percentage of kids improve with
these two methods. It is a stepwise return to weight bearing and
understanding the role of pain. Desensitization and aqua therapy
are also used. CBT includes relaxation training, biofeedback and
other coping pain skills. Many children recount that CBT helps with
daily stress and solving problems. If the pain and limb problem
becomes chronic, then treatment for depression or anxiety is considered.
Tricyclic antidepressants help with sleep and sometimes anticonvulsants
(Neurontin) are used. Finding the right dose of the right drug and
assessing side effects are all very important.Those who do not improve
with PT and CBT, can receive sympathetic blockade.
Various methods can be used from lumbar paravertebral, lumbar epidural
or IV regional with single shot or continuous methods. It depends
on the individual case. Invasive procedures are saved for those
who have tried all other therapies and did not respond well. These
treatments include spinal cord or peripheral stimulation, implantable
pumps and sympathectomy. No form of neurodestructive sympathectomy
is done due to possible long term complications.
Note: This review article appears in the Winter
Issue of the PARC PEARL.
Berde, C.B., & Sethna, N.F. (in press).
Sethna, N.F. (1999). Pharmacotherapy in long-term pain: Current
experience and future direction. In P. McGrath, & G.A. Finley
(Eds.), Chronic and recurrent pain in children and adolescents.
Progress in pain research and management (pp. 243-266). Seattle:
Sherry DD et al Short and long term outcomes of children with CRPS
1 treated with exercise therapy. Clinical Journal of Pain 1999;
Stanton, R.P., Malcolm, J.R., Wesdock, K.A., & Singsen, B.H(1993).
Reflex sympathetic dystrophy in children: An orthopedic perspective.
Orthopedics, 16, 773-779.
Wilder, R.T., Berde, C.B., Wolohan, M., Vieyra, M.A.,
Masek, B.J., & Micheli, L.J. (1992). Reflex sympathetic dystrophy
in children. Clinical characteristics and follow-up of seventy patients.
Journal of Bone & Joint Surgery American Volume, 74, 910-919.
Dr Robert Jay Schwartzman, presenter at the Tampa conference,
is a well known expert in the treatment of CRPS in children and
adults.He has been treating and researching CRPS for many years
and continues to break new ground. He was the first to document
the spread of CRPS (see Studies file) and discover the movement
disorder component of CRPS. What follows are some of his most recent
KETAMINE-MIDAZOLAM ANAESTHESIA FOR
CRPS-1 is a very hard to treat syndrome characterized by neuropathic
pain. CRPS can spread and become resistant to therapy. More treatments
are urgently needed. NMDA receptors are thought play an active role
in central pain and NMDA agonists as therapy for CRPS (and neuropathic
pain) are being studied.
Ten patients with intractable CRPS-1 were given anesthesia which
consisted of ketamine and midazolam for 5 days. Some patients were
intubated and some had spontaneous breathing. On day 6 they were
slowly tapered from infusions.
All TEN responded by having no pain, no hyperalgesia, no allodynia
and an absence of CRPS-1 signs.
Five out of ten had full pain relief for 2 months up to 3.5 years.
In 8/10 patients, after 6-8 weeks the original nociceptive pain
returned. In 7/8 the pain was at the original injury site. Hyperalgesia
and allodynia recurred in 4/10 who then received another ketamine
treatment. Success happened in 2/3. Patients were all able to use
less pain medication.
The authors are quick to say that this treatment shows potential
and could be an effective treatment option for severe CRPS-1. They
do raise the following issues: which patients would benefit most,
what selection criteria would be used to select patients, when to
treat the CRPS, and maintenance schedules for re-treatment.
This is the first attempt at using ketamine anesthesia for intractable
CRPS-1 and it does not come without its risks. Patients need to
be asleep and monitored carefully during the five day treatment.
Perhaps in future trials, a less risky form of treatment can be
Source: Schwartzman, RJ et al "Ketamine-Midazolam Anesthesia
for Intractable CRPS-1" 2002 presented to IASP 2002 Conference
SKIN BLOOD FLOW CHANGES DURING KETAMINE/MIDAZOLAM
ANESTHESIA FOR INTRACTABLE CRPS-1
Skin temperature and color changes are an integral part of CRPS.
The skin can turn blue, reddish, mottled, or purple. Temperatures
vary from hot to warm or cold. Monitoring skin blood flow changes
help clinicians decide on the effectiveness of CRPS treatments e.g.
when using sympathetic blocks. One such new promising treatment
is ketamine/midazolam anesthesia for chronic CRPS-1. This study
is the first of its kind to investigate this treatment.
Data on skin blood flow (SBF) at rest and during vasomotor ic challenge
(with heating probe) was collected. Patient's status and responses
before, during and after ketamine anesthesia were observed. Could
this method be used to asses the ability of the blood vessels to
regulate themselves or determine vasomotor impairment in CRPS? Could
this be used as a tool to assess treatment success ?
Eight patients with intractable CRPS-1 were analyzed for blood flow
with laser doppler flowmetry (PF 4001) and a heating probe was used
to raise skin temperature. Patients were measured at rest and during
the vasomotor challenge.
Under ketamine anesthesia, a significant increase in SBF was observed
in the first 72 hours. Interestingly, the areas of the most pain
showed the strongest increase, up to 10 fold. Then SBF normalized
and vasomotor reagibility occurred e.g. decreased, edema, hyperemia
and temperature changes. When the limb was locally heated, the highest
increase of SBF was found on day 2 and 3 of therapy.
The authors are the first to admit that more studies must be done
before LDF can be recommended as a diagnostic tool or for therapy.
Suggestions include monitoring SBF changes in CRPS, possibly predicting
therapeutic success, to quantify vasomotor reactive capacity (rest/vasomotor
challenge), to help assess sympathetic activity and to contribute
to a piece of the diagnostic puzzle of CRPS. Using LDF as a diagnostic
tool would be another first since there is none available at this
Source: Schwartzman, RJ et al "Skin Blood Flow Changes During
Ketamine/Midazolam Anesthesia for Intractable CRPS-1 2002
Note: Low dose ketamine treatments are now being developed
in Canada. Contact us for the name of Canadian doctors offering
ketamine treatments. These review articles can be found in the PARC
PEARL March issue.
***Argoff CE. A focused review on the use of botulinum
toxins for neuropathic pain. Clin J Pain. 2002 Nov-Dec;18(6
Cohn Pain Management Center, North Shore University Hospital, New
York University School of Medicine, Bethpage, New York 11714, USA.
Understanding the pathophysiology of a pain syndrome is helpful
in selecting appropriate treatment strategies. Nociceptive pain
is related to damage to tissues due to thermal, chemical, mechanical,
or other types of irritants. Neuropathic pain results from injury
to the peripheral or central nervous system. Common examples of
neuropathic pain include postherpetic neuralgia, diabetic neuropathy,
complex regional pain syndrome, and pain associated with spinal
cord injuries. Nociceptive pain may have similar clinical characteristics
to neuropathic pain. It is also possible for acute nociceptive pain
to become neuropathic in nature, as with myofascial pain syndrome.
A clear benefit of botulinum toxin therapy for treatment of neuropathic
pain disorders is that it often relieves pain symptoms. Although
the precise mechanism of pain relief is not completely understood,
the injection of botulinum toxin may reduce various substances that
sensitize nociceptors. As a result, botulinum toxin types A and
B are now being actively studied in nociceptive and neuropathic
pain disorders to better define their roles as analgesics.
Basford JR, Sandroni P, Low PA, Hines SM, Gehrking JA, Gehrking
TL.Effects of linearly polarized 0.6-1.6 &mgr;M irradiation
on stellate ganglion function in normal subjects and people with
complex regional pain (CRPS I). Lasers Surg Med. 2003 Jun;32(5):417-423.
Department of Physical Medicine and Rehabilitation, Autonomic Disorder
Center, Mayo Clinic and Foundation, 200 Southwest Second Street,
Rochester, Minnesota 55905.
BACKGROUND AND OBJECTIVES: Stellate ganglion blocks are an effective
but invasive treatment of upper extremity pain. Linearly polarized
red and near-infrared (IR) light is promoted as a safe alternative
to this procedure, but its effects are poorly established. This
study was designed to assess the physiological effects of this latter
approach and to quantitate its benefits in people with upper extremity
pain due to Complex Regional Pain Syndrome I (CRPS I, RSD). STUDY
DESIGN/MATERIALS AND METHODS: This was a two-part study. In the
first phase, six adults (ages 18-60) with normal neurological examinations
underwent transcutaneous irradiation of their right stellate ganglion
with linearly polarized 0.6-1.6 &mgr;m light (0.92 W, 88.3 J).
Phase two consisted of a double-blinded evaluation of active and
placebo radiation in 12 subjects (ages 18-72) of which 6 had upper
extremity CRPS I and 6 served as "normal" controls. Skin
temperature, heart rate (HR), sudomotor function, and vasomotor
tone were monitored before, during, and for 30 minutes following
irradiation. Analgesic and sensory effects were assessed over the
same period as well as 1 and 2 weeks later. RESULTS: Three of six
subjects with CRPS I and no control subjects experienced a sensation
of warmth following active irradiation (P = 0.025). Two of the CRPS
I subjects reported a >50% pain reduction. However, four noted
minimal or no change and improvement did not reach statistical significance
for the group as a whole. No statistically significant changes in
autonomic function were noted. There were no adverse consequences.
CONCLUSIONS: Irradiation is well tolerated. There is a suggestion
in this small study that treatment is beneficial and that its benefits
are not dependent on changes in sympathetic tone. Further evaluation
is warranted. Lasers Surg. Med. 32:417-423, 2003. Copyright 2003
Bennett GJ. Are the complex regional pain syndromes due
to neurogenic inflammation?
Neurology. 2001 Dec 26;57(12):2161-2.
Neurology. 2001 Dec 26;57(12):2179-84.
***Cordivari, MD 1 2, V. Peter Misra, MD, FRCP 1, Santiago Catania,
MRCP 1, Andrew J. Lees, MD, FRCP 2 *
Treatment of dystonic clenched fist with botulinum toxin.
Mov Disord. 2001 Sep;16(5):907-13.
Department of Clinical Neurophysiology, The National Hospital for
Neurology and Neurosurgery, Queen Square, London, United Kingdom
2Reta Lila Weston Institute of Neurological Studies, University
College of London, United Kingdom
email: Andrew J. Lees (email@example.com)
* Correspondence to Andrew J. Lees, Reta Lila Weston Institute
of Neurological Studies, Windeyer Building, 46 Cleveland Street,
University College of London W1T 4JF, UK
A videotape accompanies this article.
Fourteen patients with dystonic clenched fist (three with Corticobasal
Ganglionic Degeneration, seven with Parkinson's disease, and four
with Dystonic-Complex Regional Pain Syndrome) were treated with
botulinum toxin A (BTXA, Dysport®). The muscles involved were
identified by the hand posture and EMG activity recorded at rest
and during active and passive flexion/extension movements of the
finger and wrist. EMG was useful in distinguishing between muscle
contraction and underlying contractures and to determine the dosage
of BTX. All patients had some degree of flexion at the proximal
metacarpophalangeal joints and required injections into the lumbricals.
The response in patients depended on the severity of the deformity
and the degree of contracture. All patients had significant benefit
to pain, with accompanying muscle relaxation, and palmar infection,
when present, was eradicated. Four patients with Parkinson's disease
and one patient with Dystonia-Complex Regional Pain Syndrome obtained
functional benefit. © 2001 Movement Disorder Society.
Received: 18 December 2000; Revised: 4 April 2001; Accepted: 19
***Kobana,M. S. Leisa, S. Schultze-Mosgaub and F. Birklein
Tissue hypoxia in complex regional pain syndrome
c/a Neurologische Klinik, Friedrich-Alexander-Universität Erlangen-Nürnberg,
Universitätsstraße 17, D-91054, Erlangen, Germany
b Klinik für Mund-, Kiefer- und Gesichtschirurgie Friedrich-Alexander-Universität
Erlangen-Nürnberg, Universitätsstraße 17, D-91054,
Erlangen, Germany c Neurologische Klinik, Johannes Gutenberg-Universität
Mainz, Langenbeckstraße 1, D-51101, Mainz, Germany
Received 26 February 2002; accepted 6 December 2002. ; Available
online 14 May 2003.
Untreated complex regional pain syndrome (CRPS) may progress from
acute stages with increased hair and nail growth in the affected
limb to chronic stages with atrophy of the skin, muscles and bones.
The aim of this study was to investigate whether tissue hypoxia
could be one mechanism responsible for this late CRPS symptoms.
Nineteen patients with CRPS and two control groups (healthy control
subjects, surgery patients with edema) participated in this study.
Skin capillary hemoglobin oxygenation (HbO2 ) was measured non-invasively
employing micro-lightguide spectrophotometry (EMPHO). The EMPHO
probe was mounted force-controlled onto the skin of the affected
and unaffected hand. HbO2 was measured at rest and during postischemic
HbO2 did not differ between the right (58.20%±1.12) and
left (57.79%±1.31, ns) hand in control subjects. However,
in patients, HbO2 of the affected side (36.63%±2.16) was
significantly decreased as compared to the clinically unaffected
side (46.35%±2.97, P<0.01). As compared to controls, HbO2
in CRPS was reduced on both sides (P <0.001). Postischemic hyperoxygenation
was impaired on the affected side in CRPS (60.81%±2.90) –
as compared to the unaffected side (67.73%±1.50, P<0.04)
and to controls (68.63%±0.87, P<0.005). The unaffected
limb in CRPS did not differ from controls. Despite skin edema, pre-
(49.06%±2.02) and postsurgery HbO2 (53.15%±4.44, ns)
were not different in the second control group.
Our results indicate skin hypoxia in CRPS. Impairment of nutritive
blood flow in the affected limb may be one factor contributing to
atrophy and ulceration in chronic CRPS. The investigation of patients
after surgery revealed that edema could not be the only reason for
[Corresponding Author Contact Information] Corresponding author.
Tel.: +49-6131-173270; fax: +49-6131-175625
Kuczkowski, KM. Bretylium in the treatment of complex
regional pain syndrome: uncommon side-effect of a common drug. Anaesthesia
2003 Feb;58(2):201-2 Letter.
McCabe CS, Haigh RC, Ring EF, Halligan PW, Wall PD, Blake DR. A
controlled pilot study of the utility of mirror visual feedback
in the treatment of complex regional pain syndrome (type 1).
Rheumatology (Oxford) 2003 Jan;42(1):97-101
The Royal National Hospital for Rheumatic Diseases, Upper Borough
Walls, Bath BA1 1RL, UK. firstname.lastname@example.org
BACKGROUND: We assessed mirror visual feedback (MVF) to test the
hypothesis that incongruence between motor output and sensory input
produces complex regional pain syndrome (CRPS) (type 1) pain. METHODS:
Eight subjects (disease duration > or =3 weeks to < or =3
yr) were studied over 6 weeks with assessments including two controls
(no device and viewing a non-reflective surface) and the intervention
(MVF). Pain severity and vasomotor changes were recorded. RESULTS:
The control stages had no analgesic effect. MVF in early CRPS (<
or =8 weeks) had an immediate analgesic effect and in intermediate
disease (< or =1 yr) led to a reduction in stiffness. At 6 weeks,
normalization of function and thermal differences had occurred (early
and intermediate disease). No change was found in chronic CRPS.
CONCLUSIONS: In early CRPS (type 1), visual input from a moving,
unaffected limb re-establishes the pain-free relationship between
sensory feedback and motor execution. Trophic changes and a less
plastic neural pathway preclude this in chronic disease.
Parisod E, Murray RF, Cousins MJ.
Conversion disorder after implant of a spinal cord stimulator
in a patient with a complex regional pain syndrome. Anesth
Analg 2003 Jan;96(1):201-6, University of Sydney, Pain Management
& Research Centre, Royal North Shore Hospital, St. Leonards,
IMPLICATIONS: This case history describes the treatment of a patient
suffering with persistent pain. He was treated surgically with implantation
of a spinal cord stimulator. After surgery, a partial paralysis
that could not be explained medically and that was probably related
to emotional factors occurred, and cognitive behavioral treatment
was begun. This paper discusses the importance of considering social
and psychological factors when medical treatment options are considered.
***Sandroni,P., Lisa M. Benrud-Larson, Robyn L. McClelland and
Phillip A. Low Complex regional pain syndrome type I: incidence
and prevalence in Olmsted county, a population-based study
Mayo Clinic, 200 First Stret SW, Rochester, MN 55905, USA
Received 5 September 2002; accepted 9 December 2002. ; Available
online 8 May 2003.
The objective of this study is to undertake a population based
study on the incidence, prevalence, natural history, and response
to treatment of complex regional pain syndrome (CRPS). All Mayo
Clinic and Olmsted Medical Group medical records with codes for
reflex sympathetic dystrophy (RSD), CRPS, and compatible diagnoses
in the period 1989–1999 were reviewed as part of the Rochester
Epidemiology Project. We used IASP criteria for CRPS. The study
population was in the Olmsted County, Minnesota (1990 population,
106,470). The main outcome measures were CRPS I incidence, prevalence,
and outcome. Seventy-four cases of CRPS I were identified, resulting
in an incidence rate of 5.46 per 100,000 person years at risk, and
a period prevalence of 20.57 per 100,000. Female:male ratio was
4:1, with a median age of 46 years at onset. Upper limb was affected
twice as commonly as lower limb. All cases reported an antecedent
event and fracture was the most common trigger (46%). Excellent
concordance was found between symptoms and signs and vasomotor symptoms
were the most commonly present. Three phase bone scan and autonomic
testing diagnosed the condition in >80% of cases. Seventy-four
percent of patients underwent resolution, often spontaneously. CRPS
I is of low prevalence, more commonly affects women than men, the
upper more than the lower extremity, and three out of four cases
undergo resolution. These results suggest that invasive treatment
of CRPS may not be warranted in the majority of cases.
[Corresponding Author Contact Information] Corresponding author.
Tel.: +1-507-284-2090; fax: +1-507-266-6754
Schasfoort FC, Bussmann JB, Zandbergen AM, Stam HJ.
Impact of upper limb complex regional pain syndrome type
1 on everyday life measured with a novel upper limb-activity monitor.
Pain 2003 Jan;101(1-2):79-88
Department of Rehabilitation Medicine, Erasmus MC, University Medical
Center Rotterdam, PO Box 1738, 300 DR Rotterdam, Rotterdam, The
Complex regional pain syndrome type 1 (CRPS1) often leads to serious
activity limitations in everyday life. To date, however, limitations
in patients with CRPS1 of an upper limb have not been objectively
measured .Therefore, the aim of this study was to determine the
long-term impact of upper limb CRPS1 on general mobility and upper
limb usage during everyday life, as measured with a novel upper
limb-activity monitor (ULAM). In ten female chronic CRPS1 patients
and ten healthy control subjects, 24-h activity patterns were measured
with the ULAM. This ULAM consists of body-fixed acceleration sensors,
connected to a recorder worn around the waist. The ULAM automatically
detects upper limb activity during mobility-related activities.
Several outcome measures related to general mobility and upper limb
usage were compared between patients and controls. The results showed
that CRPSI in the dominant upper limb had modest impact on general
mobility; i.e. on the percentages spent in body positions and body
motions and on mean intensity of body activity. For upper limb usage
outcome measures during sitting, there was a marked difference between
CRPS1 patients and controls. Especially patients with dominant side
involvement clearly showed less activity of their involved limb
during sitting, indicated by significant differences for the mean
intensity (P=0.014), percentage (P=0.004), and proportion (P=0.032)
of upper limb activity. It is concluded that these ten chronic CRPS1
patients still had limitations in upper limb usage during everyday
life, 3.7 years (average) after the causative event.
Schouten AC, Van De Beek WJ, Van Hilten JJ, Van Der Helm FC.
Proprioceptive reflexes in patients with reflex sympathetic
Delft University of Technology, Department of Mechanical Engineering,
Man Machine Systems and Control, Mekelweg 2, 2628 CD Delft, Leiden,
Reflex sympathetic dystrophy (RSD) is a syndrome that frequently
follows an injury and is characterized by sensory, autonomic and
motor features of the affected extremities. One of the more common
motor features of RSD is tonic dystonia, which is caused by impairment
of inhibitory interneuronal spinal circuits. In this study the circuits
that modulate the gain of proprioceptive reflexes of the shoulder
musculature are quantitatively assessed in 19 RSD patients, 9 of
whom presented with dystonia. The proprioceptive reflexes are quantified
by applying two types of force disturbances: (1) disturbances with
a fixed low frequency and a variable bandwidth and (2) disturbances
with a small bandwidth around a prescribed centre frequency. Compared
to controls, patients have lower reflex gains for velocity feedback
in response to the disturbances around a prescribed centre frequency.
Additionally, patients with dystonia lack the ability to generate
negative reflex gains for position feedback, for these same disturbances.
Proprioceptive reflexes to the disturbances with a fixed low frequency
and variable bandwidth present no difference between patients and
controls. Although dystonia in the RSD patients was limited to the
distal musculature, the results suggest involvement of interneuronal
circuits that mediate post synaptic inhibition of the motoneurons
of the proximal musculature.
Singh B, Moodley J, Shaik AS, Robbs JV.
Sympathectomy for complex regional pain syndrome.
J Vasc Surg 2003 Mar;37(3):508-11
Department of Surgery, Nelson R. Mandela School of Medicine, Faculty
of Health Sciences, University of Natal, 4013 Congella, South Africa.
BACKGROUND: With the easier and earlier recognition of complex
regional pain syndrome (CRPS), a reappraisal of its therapy, particularly
the role and timing of sympathectomy, is warranted. PATIENTS AND
METHODS: Over a 9-year period, 42 patients with CRPS type II of
the upper extremity were referred for sympathectomy. Patients were
categorized according to the duration of the symptoms (group I,
<3 months; group II, >3 months). All patients underwent initial
medical treatment; stellate ganglion blocks were performed when
symptoms persisted beyond 6 weeks. Patients were referred for thoracoscopic
sympathectomy on persistence of the pain syndrome. A visual linear
analogue scale was used to evaluate outcome of sympathectomy. RESULTS:
Thoracoscopic dorsal sympathectomy was successfully undertaken in
32 patients. In the remaining 10 patients, thoracoscopy was not
technically feasible and open sympathectomy was performed. There
was an overall improvement in all 42 patients undergoing sympathectomy
(P <.001, Wilcoxon signed rank test). The outcome in group I
was significantly better than in group II (P <.003, Mann-Whitney
U test). The diagnosis of sympathetically mediated pain with stellate
blockade did not correlate with clinical outcome. Patients undergoing
thoracoscopic sympathectomy had a better outcome than those undergoing
open sympathectomy. There were no complications, and the hospital
stay was shorter in the thoracoscopic group. CONCLUSION: Early recognition
of CRPS and prompt recourse to surgical sympathectomy is a useful
option in the management of CRPS.
Son UC, Kim MC, Moon DE, Kang JK.
Motor cortex stimulation in a patient with intractable complex
regional pain syndrome type II with hemibody involvement. Case report.
J Neurosurg 2003 Jan;98(1):175-9
Department of Neurosurgery, Kangnam St. Mary's Hospital, College
of Medicine, The Catholic University of Korea, Seoul, Korea. email@example.com
The authors describe the effectiveness of motor cortex stimulation
(MCS) in a patient with complex regional pain syndrome (CRPS) Type
II, formerly known as causalgia, with hemibody allodynia. During
MCS, a subjective sensation of warm paresthesia developed in the
painful hand and forearm and spread toward the trunk. Pain and allodynia
in the areas associated with this sensation were alleviated significantly.
The analgesic effect of stimulation proved to be long lasting and
was still present at the 12-month follow up. The authors speculate
that MCS might exert its effect through the modulation of thalamic
activity in this particular case of CRPS with hemisensory deficit.
A central mechanism associated with functional disturbance in noxious-event
processing in the thalamus might have an important role in the pathogenesis
of the condition.
van de Beek WJ, Schwartzman RJ, van Nes SI, Delhaas EM, van Hilten
JJ. Diagnostic criteria used in studies of reflex sympathetic
Neurology. 2002 Feb 26;58(4):522-6.
Department of Neurology, Leiden University Medical Center, the Netherlands.
OBJECTIVE: Assessment of the diagnostic criteria of reflex sympathetic
dystrophy (RSD) and evaluation of the impact of the introduction
of the diagnostic criteria of complex regional pain syndrome (CRPS)
on the international application of diagnostic criteria of RSD.
METHODS: Randomized controlled trials and clinical investigations,
published between January 1980 and June 2000, were evaluated with
regard to the applied diagnostic criteria of RSD. RESULTS: One hundred
seven studies were identified. Thirty-four of these studies were
excluded because of inadequate reporting of diagnostic criteria.
The 73 included studies were not homogeneous with regard to the
diagnostic criteria because they applied many different aspects
of sensory and autonomic features. Only 12% of the studies considered
the presence of motor features, mostly vaguely described, as mandatory
for the diagnosis RSD. Although 10 of the 23 studies published since
the introduction of CRPS have applied this term, only 3 used the
exact criteria without additions or other modifications. CONCLUSION:
Diagnostic criteria sets of RSD focus on many different aspects
of sensory and autonomic features that generally are described vaguely.
This has not changed since the introduction of the CPRS criteria.
These findings question whether the current criteria adequately
***van de Beek WJ, Vein A, Hilgevoord AA, van Dijk JG, van Hilten
Neurophysiologic aspects of patients with generalized or
multifocal tonic dystonia of reflex sympathetic dystrophy.
J Clin Neurophysiol. 2002 Jan;19(1):77-83.
Department of Neurology, Leiden University Medical Center, 2300
RC Leiden, The Netherlands.
Reflex sympathetic dystrophy (RSD) is a syndrome dominated by sensory,
autonomic, and motor features of the extremities. In this study,
10 severely affected RSD patients who progressed to multifocal or
generalized tonic dystonia underwent H-reflex evaluation, needle
electromyography (EMG), polysomnography, somatosensory evoked potentials,
and transcranial magnetic stimulation. H-reflex evaluation revealed
an impaired vibratory inhibition of the H-reflex and a higher facilitation
peak in the recovery curve between 200 to 350 msec. Needle EMG revealed
an impaired reciprocal inhibition, and many patients were unable
to alter the amount of muscle activity voluntarily. Evaluations
of the stretch reflex showed a markedly decreased threshold and
abnormal responses to tonic and phasic changes. Polysomnography
performed in five patients revealed no abnormal EMG activity during
nonrapid eye movement and rapid eye movement sleep, but EEG arousal
phenomena provoked abnormally high and brief bursts of surface EMG
activity in all registered muscle groups. Somatosensory evoked potentials
and transcranial magnetic stimulation were normal. Taken together,
the findings in these patients with tonic dystonia of RSD are in
accordance with an impairment of inhibitory interneuronal circuits
at the level of the brainstem or spinal cord.
***van de Beeka, Willem-Johan T., Bart O. Roepb, Arno R. van der
Slikb, Marius J. Giphartb and Bob J. van Hilten,
Susceptibility loci for complex regional pain syndrome
a) Department of Neurology, Leiden University Medical Center, P.O.
Box 9600, 2300 RC, Leiden, The Netherlands b) Department Immunohematology
and Blood Transfusion, Leiden University Medical Center, Leiden,
Received 11 April 2002; accepted 22 October 2002. ; Available online
27 March 2003.
An association between HLA-DR13 and patients with complex regional
pain syndrome (CRPS) who progressed towards multifocal or generalized
tonic dystonia was recently reported. We now report on a new locus,
centromeric in HLA-class I, which was significantly associated with
a spontaneous development of CRPS, suggesting an interaction between
trauma severity and genetic factors conferring CRPS susceptibility.
Additionally, an association with the D6S1014 locus was found, supporting
the previous finding of an association with HLA-DR13.
[Corresponding Author Contact Information] Corresponding author.
Tel.: +31-71-526-2895; fax: +31-71-524-8253
NOVEMBER 14-15 , 2003.
RSD AND THE SYMPATHETIC NERVOUS SYSTEM
R. Baron, Klink fur Neurologie, Christian-Alrechts-Universitat,
The striking response of neuropathic pain syndromes such as CRPS
(CRPS, causalgia) and RSD to
sympatholytic procedures together with signs of autonomic nervous
system abnormalities suggest that the
sympathetic efferent system can generate or enhance pain (SMP) and
may be involved in the dysregulation of skin blood flow and sweating.
Evidence from animal experiments: There is convincing evidence from
animal studies that after complete and partial nerve injury both
damage and undamaged nociceptive C-fibers acquire a chemical sensitivity
to noradrenergic agents and can be activated by sympathetic - trunk
stimulation. This sympatho-afferent transmission is mediated by
alpha 2 adrenoreceptors Accordingly, mRNA for alpha 2-Aadrenoreceptors
is up-regulated in DRG neurons after nerve transection.
Pathophysiology of SMP in patients: The adrenergic influence on
afferents in humans was analyzed in
patients with CRPS type 2. In a subgroup of patients with SMP, intracutaneous
alpha-adrenergic agents enhances pain and hyperalgesia. Accordingly,
autoradiographic studies indicate
that the number of alpha-1-adrenorecptrs in hyperalgesic skin of
patients with SMP is significantly greater
than in the skin of normal subjects. Further more, it could be demonstrated
in CRPS1 that spontaneous
pain and mechanical hyperalgesia was augmented when sympathetic
cutaneous vasoconstrictor neurons
were activated physiologically by thermoregulatory cold stress.
There was a high correlation between pain relief during sympathetic
blocks and augmentation of pain during sympathetic chain activation.
The latter results show that also sympathetic activity modulated
in physiological ranges and endogenous
noradrenaline release is able to enhance pain in CRPS.
Autonomic abnormalities in patients: Controlled thermoregulatory
reflexes (Whole body warming, cooling) were used to experimental
regulation patterns were identified related to the duration of the
disorder: in the warm regulation type (acute stage) the affected
limb was warmer and skim perfusion values were higher than contralaterally
during the entire spectrum of sympathetic activity, Even massive
body cooling failed to activate sympathetic vasoconstrictor neurons.
In the intermediate type temperature and perfusion were either warmer
or colder depending on the degree of sympathetic activity. In the
cold type (Chronic stages) temperature and perfusion were lower
on the affected side during the entire thermoregulatory cycle.
In conclusion, a central unilateral inhibition of cutaneous sympathetic
vasoconstrictor neurons leads to a
warmer affected limb in the acute stage. Secondary changes in the
neurovascular transmission induce
vasoconstriction and cold skin in chronic CPRS. The maximal skin
temperature difference between the
affected and unaffected extremity that occurs during the theromregulatory
cycle can be sued as a
diagnostic tool. With high sensitivity and specificity it distinguishes
CRPS from other extremity pain
INFLAMMATION AND RSD
RJA Goris, MD University Hospital Nijmegen, Dept. of Surgery, Nijmegen.
The majority of scientific publications on RSD/CRPS I address late
problems relating to pain, tissue
dystrophy, and atrophy and neurological changes. However, in the
early phase, signs and symptoms of
inflammation are prominent. Acute inflammation in RSD could be documented
by studying the
extravasation of immunoglobulin in the affected extremity. Also,
morphologically, signs of tissue damage
could be demonstrated in skeletal muscle, related to tissue damage
caused by toxic oxygen radicals. Such
alterations could be reproduced in an experimental model of oxygen
radical-induced skeletal muscle
damage in the rat. The therapeutic effect of oxygen radical scavengers
and corticosteroids in acute RSD
also indicates the role of these compounds in generating pathological
The problem of performing “normal” skeletal muscle work
with an RSD-affected extremity was objectified by NMR-spectroscopy
studies indicating that at tissue level, the supply and or utilization
of oxygen in impaired. which also is a characteristic encountered
in severe inflammation. As a consequence oxygen extraction in the
affected limb is impaired, as shown by elevated venous oxygen saturation
levels. In a recent study, the inflammatory response to a Colles
fracture was prospectively studied in 115 patients. A wide variety
was found in the severity of the inflammatory reaction, After one
year. follow-up, the incidence of RSD in these will be documented
and the early response related to late RSD.
Many problems still have to be elucidated in RSD such as why patient
develops RSD and most others do
not. Studying the genetic characteristics in respect to generating
an exaggerated inflammatory response,
may be one of the pathways to explore further.
1. Veldman PHJM et al Signs and symptoms of RSD
2. Goris RJA RSD World Jour Surg 1998
3. van der Laan L Goris RJA Sudeck Syndrome Unfallchir 1997
4. van der Laan, Goris RJA RSD Hand Cline 1997
5. Oyen WJG et al RSD of the hand Pain 1993
6. van der Laan et al CRPS 1 RSD Neurology 1998
7. van der Laan L et al A novel animal model Free Rad Res. 1997
8. Goris RJA et al Are toxic oxygen radical... Free Rad RES Comms
9. Heereschap A et al; Metabolic changes in RSD Muscle Nerve 1993
10. Goris RJA Conditions associated with impaired O2 extraction
Springer Verlag 1991
11. Vaneker M et al Genetic factors associated with CRPS Disability
NEUROGENIC INFLAMMATION IN RSD
F Birklein, Dept. of Neurology, University Clinic, Mainz, Germany.
Many clinical symptoms of acute CRPS resemble inflammation--pain,edema,
increased skin temperature
and blood flow. However, inflammation in the classical sense has
not been unequivocally proven. Rather
the coincidence, of inflammatory signs with trophic changes (hair,
growth, high-turnover osteoporosis) and mechanical hyperalgesia
without hyperalgesia to heat strongly suggests “neurogenic”
Trauma related activation of primary afferents cause neuropeptide
release in the affected body region
(mainly substance P (SP) and calcitonin-gene related peptide (CRGP)
and chronic release of neuropeptides might be responsible for the
above mentioned peripheral CRSP symptoms. In addition, central neuropeptide
release facilitates nociceptitve sensitization and may cause motor
After experimental nerve lesions experiments in rats have shown
that neuropeptides, in particular SP,
contribute to pain behaviour and many clinical symptoms resembling
CRPS. In analogy to migraine studies, we therefore measure CGRP
(RIA) in serum samples from patients with acute CRPS. CGRP was significantly
increase, in particular when clinical inflammatory signs were pronounced
and if there was
evidence for trauma related nerve lesion. In order to verify that
increased CGRP indeed comes from
primary nociceptive afferents, neurogenic inflammation was elicited
directly in the skin by transcutaneous
electrical stimulation via intraderrmal microdialysis capillaries,
We first investigated the flare by
Laser-Doppler scanning on the affected and on the unaffected side
in our CRPS patients. Neurogenic
flare was significantly more intense in patients, surprisingly on
both side, the affected and the
clinically unaffected one.
Another characteristic of neurogenic inflammation in rodents is
SP mediated plasma protein extravasation
(PPE). IN health humans, however, there are regularly too few SP
containing C fibers for PPE. In CRPS, however, significant PPE could
be shown in almost all patients investigated. In contrast to the
flare response this increased PPE was limited to the affected side.
These results so far suggested two possible pathomechanisms leading
to facilitated neurogenic inflammation in CRPS--either increased
release or hampered inactivation of neuropeptides. In order to further
unravel this mechanisms we perfused SP in ascending concentrations
through dermal microdialysis fibers, We found SP significantly more
effective to induce PPE in CRPS patients than controls. Alike increased
flare, this increase responsiveness to SP was present on both the
affected and unaffected limbs.
To summarize, our investigations: we found evidence that neurogenic
inflammation may be essential
to explain many symptoms of CRPS. There must be a trauma-related
upregulation of neuropeptide
release from primary afferents on the affected side. However, in
addition, there must be constitutionally
impaired inactivation of neuropeptides which predisposes some subjects
to develop CRPS in response to
SPINAL CORD STIMULATION IN PATIENTS WITH CRPS TYPE 1:
LONG TERM RESULTS(translation)
M van Kleef, AZ Maastricht, Dept. of Anesthesiology and Pain Management,
Spinal cord stimulation (SCS) has been used since 1967 for treating
chronic pain patients. Since the
beginning of the 90’s it has been used to treat CRPS type
1. In 1997, AZM, compared research of the
effects of SCS with chronic pain patients and those with CRPS. From
this study you can see that after one half year significant reduction
in pain perception and quality of life with patients treated with
During his speech he will discuss possible mechanisms of neuropathic
pain. He will also announce clinical
long term effects after 6 months, in 36 patients with subcutaneous
implants they were followed. Pain scores were examined 6 months,
1 and 2 years after implantation. With all the patients there was
a pain diary and quality of life was measured by scientific testing
The result was that the pain was clearly reduced in 1 year and
2 years after implantation. There was still
significant reduction of VAS score. 42% of CRPS type 1 in UE and
47% of CRPS I LE reported that since the beginning of treatment
they were much improved. Also the quality of life scale was clearly
improved after treatment. In conclusion SCS pain intensity with
majority of patients with CRPS-I reduced pain and quality of life
improved. No significant difference in outcome between patients
with cervical or lumbar SCS.
PSYCHOLOGICAL ASPECTS OF CRPS
EC Covington, Cleveland Clinic Foundation, Pain Rehabilitation Program,
Cleveland Ohio USA
Historically, CRPS has been strongly associated with psychological
disorder and several relationships have been proposed: 1) CRPS is
a psychiatric (somatoform/conversion) disorder; 2) psychiatric
illness/personality disorder create a predisposition to the development
of CRPS; 3) CRPS causes
psychiatric illness; 4) psychological factors modify the course
of CRPS and 5) adjustment and function in
CRPS are determined by psychological factors. These ideas derived
from the obscure nature of the disease and the marked discordance
between the often trivial injury and the severity of complaints
and spread of symptoms. It is also likely that failures of coping
and adaptation are disproportionately represented among intractable
cases, and that patients in pain centers (where CRPS has been studied)
have more psychopathology than those in the community.
The myth of CRPS as a psychogenic condition has faded in the face
of substantial evidence that the
psychopathology in these patients does not differ appreciably from
that in others with chronic pain. It has
been further weakened by studies showing genetic determinants of
that illness and evidence of central
reorganization with thalamic and cortical changes.
One origin of the myth of psychogenicity in CRPS may be that the
condition is relatively easy to simulate.
Several patients with “typical RSD” had clear evidence
of a ligature on the arm or leg. Less obvious cases of self-inflicted
disease or exacerbation have involved prolonged dependency and forced
posturing. These conditions constitute “faux CRPS” and
the patients are profoundly psychiatrically
The major sequela of CRPS is depression. Axis II disorders are
reportedly common as well; however,
severe pain and disability produce such profound changes in “personality”
that these disorders are
probably not true personality disorders, but maladaptive attitudinal
and behavioural responses
induced by the disease. A psychophysiologic component to CRPS is
suggested by the studies of
stress at onset and by the fact that autonomic arousal increase
The influence of behavioral factors on the course of CRPS is suggested
by the fact that disuse produces a
clinical picture similar to that of CRPS. and exercise and mobilization
have been shown to reverse edema,
trophic changes and vasomotor signs.
Cognitive factors are likely to play a role in the person’s
ability to cope with the pain of CRPS and issues
of gain/reinforcement/reward influence coping behaviour as well.
While psychological issues do not explain CRPS, they do play a
major role in its treatment and in the
response to such invasive treatments as spinal cord stimulation.
Cognitive therapies and interventions
focused on improved physiologic self regulation (biofeedback training,
autogenic training, self hypnosis)
are most important. Formal behaviour modification may be required
to assist the difficult patient to initiate
a recovery program and family members must be partners in this endeavor.
Multidisciplinary pain rehabilitation, with simultaneous focus
on symptom control, physical rehabilitation,
psychotherapy and behavioral management is probably the best option
for patients who fail less extensive
There is no such thing as an RSD personality. There is no personality
for asthma or migraine either.
Extreme behaviour after a minor injury is questioned by doctors.
They take the attitude: “If I can’t see it, it does
not exist”. Since there is no single test for CRPS, “if
I can’t explain it with evidence, then it does not exist”.
This is an inaccurate conclusion from tertiary care doctors.
There is no difference between CRPS and lower back pain patients.
CRPS patients were less depressed and scored lower on hysteria in
a recent study.
The mind plays a role in suffering: we either cope or do not adapt.
What is a personality? We think, feel
and behave. An irritable bladder or bowel or chest pain is not perceived
as psychogenic, why should
With visceral CPRS in the organs ie. bladder, bowel etc. those
with high anxiety develop visceral
hyperalgesia easily. ( Gunter 2000.)
“Limbically augmented pain syndrome” is a sensitization
process in some chronic pain patients where loud
noises result in seizures. Also “polymodial allodynia”
is where the noise causes pain or trauma and
psychological stress. (Rome Pain Med 2000)
Suffering is the emotional part of pain. In pain centers the most
common is anxiety. In 104 CRPS patients, 96% suffer from chronic
depression. (Rudy,TE Pain 1988) there is a definite link between
pain and depression. It needs interference to break the link e.g.
a control factor like therapy.
In lower extremity CRPS 79.2% experienced major stress at the onset
of CRPS. Therefore, we can
conclude that high stress predisposes someone to CRPS.
In behaviour, the stigma of CRPS is that patients are “poorly
motivated to get well and they do not make
the effort”. Active exercise can reverse edema and disuse
is detrimental. Cognition and pain lead to
misinformation e.g. that pain means body damage and that they are
helpless and fragile. This leads to
inactivity which results in deconditioning and it becomes a cycle
of pain and disability.
Learned helplessness is found in many chronic pain patients. You
are not fragile or powerless. We need to empower them and give them
a sense of control. Good behaviour should be rewarded. Immediate
consequences: if it feels good now it may be bad for you later.
ie. resting too much and not exercising
Many chronic pain patients do not do well in treatment if they
continue to look for who is at fault. They
will have a poor response to treatment and blame is toxic.
There is no data on “psuedo-CRPS” like ligatures, forced
dependency or posture. Doctors need to make
the correct diagnosis.
“Chronic pain changes who you are”. Stress can make
CRPS worse. It is rare that it is self-induced. There is cross talk
between nerves: emotional allodynia cause organic allodynia.
IS THERE A GENETIC EXPLANATION FOR CRPS? (translation)
Prof WAA Zuurmond, University of Amsterdam, Amsterdam.
CRPS is a complication that can occur after a trauma or operation
to an extremity. Patients can become
quite disabled, to losing total function in an affected extremity.
Not everyone develops CRPS after a
trauma or operation. Why is this complication in one patient and
not in another?
The symptoms of CRPS resemble an exaggerated inflammatory reaction.
Could CRPS be the result of an
exaggerated inflammatory response from an anti stress or anti-immune
CRPS is neurogenic inflammation. Is it an auto-immune response?
Many diseases have HLA factors e.g.
MS. Is HLA the initiator in CRPS? Is the modulator TNF? The HLA
molecule has various parts A and B.
Method: A control group of 1,000 and 161 CRPS
patients were typed for HLA A and B. then TNF-a using PCR-SSP-SSO-ELISA
typing. Results were:
|HLA-DR 6(cold RSD)
|Subgroup(more than one extremity)
Patients in subgroup have HLA-TNF-a2 association. This result needs
research on treatments that will have an effect on TNF-a.
*from Dutch Conference handouts and lecture notes from attendees.
Special thanks to Marijn Birnie for translations.
STUDIES 2002: A-M
Berde CB,Lee BH, Scharff L, Sethna NF, McCarthy CF, Scott-Sutherland
J, Shea AM, Sullivan P, Meier P, Zurakowski D, Masek BJ.Physical
therapy and cognitive-behavioral treatment for complex regional
pain syndromes. J Pediatr 2002 Jul;141(1):135-40 Pain Treatment
Service and the Departments of Physical Therapy, Orthopaedic Surgery,
and Psychiatry, Children's Hospital, Boston, Massachusetts.
Complex regional pain syndromes (CRPS; type 1, reflex sympathetic
dystrophy, and type 2, causalgia) involve persistent pain, allodynia,
and vasomotor signs. We conducted a prospective, randomized, single-blind
trial of physical therapy (PT) and cognitive-behavioral treatment
for children and adolescents with CRPS. Children 8 to 17 years
of age (n = 28) were randomly assigned to either group A (PT once
per week for 6 weeks) or group B (PT 3 times per week for 6 weeks).
Both groups received 6 sessions of cognitive-behavioral treatment.
Assessments of pain and function were repeated at two follow-up
time periods. Outcomes were compared at the three time points
through the use of parametric or non parametric analysis of variance
and post hoc tests. All five measures of pain and function improved
significantly in both groups after treatment, with sustained benefit
evident in the majority of patients at long-term follow-up. Recurrent
episodes were reported in 50% of patients, and 10 patients eventually
received sympathetic blockade. Most children with CRPS showed
reduced pain and improved function with a noninvasive rehabilitative
treatment approach. Long-term functional outcomes were also very
Bruehl S, Harden RN, Galer BS, Saltz S, Backonja M, Stanton-Hicks
M. Complex regional pain syndrome: are there distinct subtypes
and sequential stages of the syndrome?Pain 2002 Jan;95(1-2):119-24
Department of Anesthesiology, Vanderbilt University School of
Medicine, Vanderbilt University Medical Center, Suite 403-G MAB,
1211 Twenty-First Avenue South, 37232-1557, Nashville, TN, USA
This study tested for evidence supporting the clinical lore of
three sequential stages of complex regional pain syndrome (CRPS)
and examined the characteristics of possible CRPS subtypes. A
series of 113 patients meeting IASP criteria for CRPS underwent
standardized history and physical examinations to assess CRPS
signs and symptoms in four domains identified in previous research:
pain/sensory abnormalities, vasomotor dysfunction, edema/sudomotor
dysfunction, and motor/trophic changes. K-Means cluster analysis
was used to derive three relatively homogeneous CRPS patient subgroups
based on similarity of sign/symptom patterns in these domains.
The resulting CRPS subgroups did not differ significantly regarding
pain duration as might be expected in a sequential staging model.
However, the derived subgroups were statistically-distinct, and
suggested three possible CRPS subtypes: (1) a relatively limited
syndrome with vasomotor signs predominating, (2) a relatively
limited syndrome with neuropathic pain/sensory abnormalities predominating,
and (3) a florid CRPS syndrome similar to 'classic RSD' descriptions.
Subtype 3 showed the highest levels of motor/trophic signs and
possible disuse-related changes (osteopenia) on bone scan, despite
having directionally the briefest pain duration of the three groups.
EMG/NCV testing suggests that Subtype 2 may reflect CRPS-Type
2 (causalgia). Overall, these results are consistent with limited
previous work that argues against three sequential stages of CRPS.
However, several distinct CRPS subtypes are suggested, and these
could ultimately have utility in targeting treatment more effectively.
Graham LE, McGuigan C, Kerr S, Taggart AJ. Complex regional
pain syndrome post mastectomy Orthop Ihre Grenzgeb 2001 Sep-Oct;139(5):452-7
Rheumatol Int 2002 Jan;21(4):165-6 Registrar in Rheumatology,
Musgrave Park Hospital, Belfast, Northern Ireland. firstname.lastname@example.org
Complex regional pain syndrome includes the previously termed
condition reflex sympathetic dystrophy. It is a chronic pain disorder
diagnosed on the basis of symptoms and skin changes and is known
to have a psychological element. It is a rare complication after
surgery, especially mastectomy. We present two females who developed
this syndrome after undergoing mastectomy for chronic mastalgia.
These cases demonstrate that amputation of an organ for chronic
pain can result in reflex sympathetic dystrophy developing in
a nearby limb.
Rho RH, Brewer RP, Lamer TJ, Wilson PR Complex regional pain
syndrome.Mayo Clin Proc 2002 Feb;77(2):174-80 Division of Pain
Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Complex regional pain syndrome (CRPS), formerly known as reflex
sympathetic dystrophy, is a regional, posttraumatic, neuropathic
pain problem that most often affects 1 or more limbs. Like most
medical conditions, early diagnosis and treatment increase the
likelihood of a successful outcome. Accordingly, patients with
clinical signs and symptoms of CRPS after an injury should be
referred immediately to a physician with expertise in evaluating
and treating this condition. Physical therapy is the cornerstone
and first-line treatment for CRPS. Mild cases respond to physical
therapy and physical modalities. Mild to moderate cases may require
adjuvant analgesics, such as anticonvulsants and/or antidepressants.
An opioid should be added to the treatment regimen if these medications
do not provide sufficient analgesia to allow the patient to participate
in physical therapy. Patients with moderate to severe pain and/or
sympathetic dysfunction require regional anesthetic blockade to
participate in physical therapy. A small percentage of patients
develop refractory, chronic pain and require long-term multidisciplinary
treatment, including physical therapy, psychological support,
and pain-relieving measures. Pain-relieving measures include medications,
sympathetic/somatic blockade, spinal cord stimulation, and spinal
Weber M, Neundorfer B, Birklein F. Sudeck's atrophy: pathophysiology
and treatment of a complex pain syndrome Dtsch Med Wochenschr
2002 Feb 22;127(8):384-9 Neurologische Klinik (Direktor: Prof.
Dr. B. Neundorfer), Friedrich-Alexander-Universitat Erlangen.
Sudeck's atrophy: pathophysiology and treatment of a complex
pain syndrome. SUMMARY: The "Morbus Sudeck" or Complex
Regional Pain Syndrome (CRPS) forms a typical triad of motor,
sensory and autonomic symptoms. It is clinically characterized
by spontaneous pain and hyperalgesia not limited to a single nerve
territory and disproportionate to the inciting event. An underlying
pathophysiology which could explain the whole symptomatology of
CRPS is still unknown. Therefore, nowadays therapy is still symptomatic.
However, recent research led to a better understanding of the
disease and to the beginning of a pathophysiologically orientated
Zuniga RE, Perera S, Abram SE. Intrathecal baclofen: a useful
agent in the treatment of well-established complex regional pain
syndrome.Reg Anesth Pain Med 2002 Jan-Feb;27(1):90-3 Department
of Anesthesiology and Critical Care Medicine, University of New
Mexico School of Medicine, Albuquerque, New Mexico 87131-5216,
BACKGROUND AND OBJECTIVES: We present 2 case reports that illustrate
that chronic intrathecal (IT) baclofen administration may be efficacious
in treating patients with long-standing complex regional pain
syndrome, type I (CRPS I) who have failed treatment with multiple
drugs and procedures.
CASE REPORTS: Both cases presented were women who developed CRPS
I following multiple lower extremity surgeries. One patient had
had symptoms for 5 years and had continued symptoms despite multiple
sympathetic blocks, sympathectomy, spinal cord stimulation, and
various medication trials. The other patient had had chronic lower
extremity pain for 30 years and symptoms of CRPS for about 5 years.
Her symptoms continued despite multiple sympathetic blocks, sympathectomy,
and many medications. Neither patient had motor dysfunction (dystonia,
tremors, spasticity) associated with their painful disorder. One
patient experienced good control of pain, allodynia, and autonomic
dysfunction with a combination of IT baclofen and clonidine after
failing treatment with IT morphine. Baclofen alone produced intolerable
side effects at the doses required to produce adequate analgesia.
The other patient experienced long-term control of pain, allodynia,
and autonomic symptoms with IT baclofen alone.
CONCLUSIONS: IT baclofen appears to be an option for patients
with intractable CRPS who have failed other modalities, including
IASP (International Association
for the Study of Pain) Congress
San Diego, CA
August 15, 2002.
The following studies will be presented at this congress. Many
of these studies are being developed as new treatment options
Studies are listed by abstract number.
Abstract ID: 1218-P134
IMPROVED TECHNIQUES FOR EXAMINATION AND TREATMENT OF COMPLEX REGIONAL
PAIN SYNDROME (CRPS) - A PILOT STUDY.
M. Imamura1, S.T. Imamura1, A.A. Fischer2, D.A. Cassius3, A.E.
Carvalho Jr1 1 Division of Physical Medicine, Foot Clinic, Dept.
Orthopaedics and Traumatology, University of So Paulo, São
Paulo, Brazil , 2 Mount Sinai School of Medicine, New York, NY
, 3 Moss Bay Center, Seattle, WA
Aim of Investigation: To evaluate improved techniques for examination
and treatment of CRPS of the lower limbs.
Methods: Fourteen adult patients with CRPS I (12) and II (2) of
the lower limbs, of various etiologies, for mean duration of 14.6
months were evaluated. Patients were tested for dermatomal hyperalgesia
by a skin scratch test, pinching and rolling the skin, and electric
skin conductance. Myotomal hyperalgesia was evaluated based on
the presence of muscle spasm, taut bands, trigger points (TrPs)
and tender spots (TSs). All patients received tricyclic antidepressants,
neuroleptics, non- steroidal anti-inflammatory drugs, analgesics
and a functional rehabilitation pro gram. Treatment was combined
with paraspinous blocks, pre injection blocks and needling and
infiltration of taut bands, TrPs and TSs, when a segmental sensitization
was diagnosed. Pain intensity was evaluated by visual analog scale
(VAS) before and after treatment.
Results: VAS values reduced (p=0.002) from 9.11.4 to 5.12.7 with
treatment. The dermatomal hyperalgesia present prior to treatment
was reduced towards normalization. Spasm and TrPs in the corresponding
myotome became less tender. A segmental distribution of sensitization
was noted at multiple (2-3) levels in 85.7% of the patients.
Conclusions: Improved examination techniques showed that pain
in CRPS is frequently manifested as a sensitization in a spinal
segmental distribution. By treating the spinal segmental sensitization,
CRPS patients had a significant reduction in their pain intensity.
Abstract ID: 1217-P133
COMPLEX REGIONAL PAIN SYNDROME PRESENTS IN IDENTICAL TWINS
L.L. Brown, M. Stanton-Hicks Pain Management Center, Cleveland
Clinic Foundation, Cleveland, OH
Aim of Investigation: To report the occurrence of complex regional
pain syndrome in a set of identical twin sisters. To review the
literature and to discuss the contribution of this case to the
growing body of evidence suggesting a genetic influence in the
development of complex regional pain syndrome.
Methods: Chart review was conducted for two identical twin sisters.
History of original injury, disease progression and response to
diagnostic and therapeutic procedures is reported.
Results: Identical twin sisters, aged 36, both sustained work
related injuries to their right ulnar nerves that progressed to
complex regional pain syndrome. Original evaluations, including
radiographs, electromyelograms, and nerve conduction studies were
normal. After a prolonged course of various failed therapeutic
modalities, Twin A had a peripheral nerve stimulator implanted.
Twin B is currently receiving a course of bier block treatments
awaiting approval for a peripheral nerve stimulator.
Conclusions: A linkage between neuropathic pain and a single autosomal
recessive gene has been demonstrated in mice.1 Further work has
suggested an HLA antigen association with complex regional pain
syndrome.2,3 This is the first case report of complex regional
pain syndrome existing in human identical twins. The development
of symptoms in the same limb further lends support to a potential
genetic component predisposing one to this chronic neuropathic
Key Words: complex regional pain syndrome; reflex sympathetic
dystrophy; heredity; MHC-HLA References: 1. Devor M, Raber P.
Pain, 42,1990, 51-67. 2. Kemler MA. Neurology, 53, 1999, 1350-51.
3. Mailis A, Wade J. Clin Jrnl Pain, 10(3), 1994, 210-17.
Abstract ID: 1216-P132
CORRELATION BETWEEN CUTANEOUS TROPHIC CHANGES AND MYOCARDIAL INFARCTION
R. Casale1, T. Savarin2, S. Pieropan2, P. Mazzi2, B. Sommovigo3
1 Clin. Neurophysiology, "S.Maugeri" Found. Rehabil.
Institute, Montescano (PV), Italy , 2 Dept. Internal Med., Univ.
of Verona, Verona, Italy , 3 European School of MCR, Pavia, Italy
Introduction. Pain from myocardial infarction (MI) can be referred
to superficial and deep somatic structures and also generate skin-referred
trophic changes. Connective tissue massage is a physiotherapeutic
technique consisting in the recognition of specific areas of dorsal
cutaneous altered trophism, empirically related to the presence
of visceral pathologies, the lateral subscapular cutaneous area
(SSCA) being related to cardiac diseases. The aim of this preliminary
study was to determine whether MI positively correlates with trophic
alterations in SSCA.
Methods. 24 consecutive non-randomized pts (8M; 16M mean age 41)
referred to an Emergency Unit for chest pain were studied. Immediately
after the clinical stabilization, independent observers scored
the presence or absence of SSCR. Troponin (TP) levels (TP<0.1mg/ml
= normal, TP>3 mg/ml = myocardial necrosis) were recorded by
other independent observers. Results. 7 out of 24 patients had
a final diagnosis of a painful cardiac disease with increased
TP levels (6 MI, 1 myocarditis): 6 had SSCA trophic changes. 17
had a generic diagnosis of chest pain of non-cardiac origin: only
5 had positive SSCA changes. (Fisher's test: p = 0.023; Sensitivity
= 6/7 = 86%; Specificity = 12/17 = 71%; Positive predictive value
= 6/11 = 54%; Negative predictive value = 12/13 = 92%).
Conclusion. Trophic changes in SSCA positively and statistically
correlate with biohumoral indices of MI pointing out that acute
cardiac pain due to MI can acutely induce skin-referred trophic
changes. The absence of trophic changes also has a relevant predictive
value in detecting non-cardiac pain (92%).
Abstract ID: 1215-P131
PAIN-CORRELATED REORGANIZATIONAL PROCESSES OF THE SOMATOSENSORY
CORTEX IN PATIENTS WITH COMPLEX REGIONAL PAIN SYNDROME I (CRPS
B. Pleger1, P. Schwenkreis1, F. Janssen1, O. Rommel1, P. Ragert1,
B. Vlker2, C. Maier2, M. Zenz2, M. Tegenthoff1
1 Neurology, Kliniken Bergmannsheil, Ruhr-University, Bochum,
Germany , 2 Anaesthesiology, Kliniken Bergmannsheil, Ruhr-University,
Aim of Investigation: In the case of CRPS, the involvement of
the central nervous system in the development of pain stays unsolved.
The aim of this study was to determine, if there are pain-correlated
representational changes of the somatosensory cortex in CRPS.
Methods: We performed a SSEP mapping in 7 patients with CRPS I
of one upper limb with electrical stimulation of the median and
ulnar nerve to get an idea of the magnitude of hands representational
Results: We found a significant smaller Euclidean distance between
the median and the ulnar nerve N20-dipole localizations of the
somatosensory cortex contralateral to the CRPS-affected limb.
The difference between the polar angels of the N20-dipole localizations
of both nerve representations mirrored a smaller representational
field of the CRPS-affected hand. The mean pain value was correlated
with the changes of the corresponding representational field of
the affected limb. Little actual pain was associated with small
changes of the representational field, while subjects with large
cortical reorganization complained high pain levels.
Conclusions: Cortical reorganization processes of hands` representational
field seem to be closely related to the amount of nociceptive
processing. Probably, pain-related thalamic hyperactivity leading
to a disturbed input in post-connected somatosensory pathways
might explain our findings of a smaller cortical representation
area of the CRPS-affected hand.
Abstract ID: 1214-P130
COMPLEX REGIONAL PAIN SYNDROME: FIRST DATA OF A PROSPECTIVE STUDY
EVALUATING THE EFFICACY OF REGIONALLY ADMINISTRED GUANETHIDINE
L. Demartini1, R. Bettaglio1, M. Allegri1, G. Bonetti1, A. Violini1,
A. Braschi2, A. Nava1 1 palliative care and pain therapy, Fondazione
Maugeri, Pavia, Italy , 2 anesthesia and intensive care institute,
Pavia's University, Pavia, Italy
Aim of investigation: We planned a study to evaluate the short
and long term efficacy of regional sympathetic blockade with guanethidine
in patients with CRPS with pain scales (Neuropathic Pain Scale
and Brief Pain Inventory).
Methods: Since January 2001 we enrolled 17 patients fulfilling
the IASP criteria for CRPS. All of them were studied with bone
scintigraph, telethermography and TcPO2 to evaluate vasomotor
changes, QST and von Frey needling for sensory changes; NPS and
BPI were applied. A great majority of patients had already received
other treatments prior to the study with no or poor effect. The
patients were treated with a course (six) of regional sympathetic
blockades according to the technique of Hannington-Kiff and then
they were revalued. When pain and impairment improved but still
persisted the patients underwent another course of blockades and
were then revalued.
Results: The NPS values, after treatment (first course), show
a significant reduction in all items, specially pain intensity
(from 7.23 to 3.17); deep pain intensity (from 7.64 to 3.83) improves
more than surface pain intensity (from 3.76 to 2.47). BPI values
show a reduction not only of pain intensity but also of functional
impairment in daily living (from 7.82 to 3.58) and sleep (from
5.86 to 1.88).
Conclusions: Pain has various mechanisms in CRPS. With this study
it seems that regional sympathetic blockade is not only effective
on pain but also (specially) on functional impairment. We saw
improvement of edema and joint movement before reduction of pain.
These data justify further evaluation.
Abstract ID: 1213-P129
COMPARATIVE EVALUATION OF THREE THERAPEUTIC MODALITIES FOR MANAGEMENT
OF CRPS TYPE I OF UPPER EXTREMITIES: INTRAVENOUS REGIONAL BLOCK
WITH BRETYLIUM, INTRAVENOUS REGIONAL BLOCK WITH GUANETHIDINE AND
INTERMITTENT STELLATE GANGLION BLOCKS WITH BUPIVACAINE
G.P. Dureja, T. Jayalakshmi, B. Ghai, S. Prakash, H.L. Kaul Pain
Clinic, All India Inst of Med Sciences, New Delhi, India
AIM OF INVESTIGATION: To evaluate three different therapeutic
modalities for management of CRPS Type I of upper extremities
in a randomized prospective clinical trial.
METHODS: Sixty-four consecutive patients with CRPS-I of upper
extremity were the subjects of this study. After a clinical evaluation
for diagnostic criterion of CRPS-I, a 3-Phase Bone Scan was done
to confirm the diagnosis. The patients were then randomly assigned
to receive either stellate ganglion blocks with 10 ml of 0.25%
Bupivacaine on alternate days for a maximum of 10 blocks (Group
A, n=23) or, IVRA with 1.5 mg/kg Bretylium and 10 mg lidocaine
(30 ml volume) repeated twice at 15 days interval (Group B, n=21)
or, IVRA with 0.3 mg/kg Guanethidine and 10 mg lidocaine (30 ml
volume) (Group C, n=20) repeated twice at 15 days interval. Various
objective parameters evaluated included digital plethysmography,
telethermometry, doppler flowmetry and scoring of Pain relief,
edema and range of motion on a 0-10 score. Minimum follow up duration
was 6 months and complete pain relief and functional improvement
was considered as successful outcome.
RESULTS: IVRA with Bretylium resulted in an earliest (mean 6.3
days) and maximum relief in pain (VAS <3), and functional parameters
in 20 out of 23 patients (P<0.01). Intermittent stellate ganglion
blocks provided relief in pain (VAS<5) and functional parameters
in 15/21 patients. IVR block with Guanethidine was least effective
and only 3 out of 20 patients had acceptable pain relief.
CONCLUSIONS: Intravenous regional block with Bretylium resulted
in a successful outcome in 86.8% patients with CRPS-I.
Abstract ID: 1212-P128
PSYCHONEUROPATHOLOGICAL FEATURES OF CUTANEOUS HYPERALGESIAS/ALLODYNIAS
IN CRPS I AND II.
R.J. Verdugo, L.A. Bell, M. Campero, F. Salvat, B. Tripplet, J.
Sonnad, J.L. Ochoa Oregon Nerve Center, OHSU, Portland, OR
Aim of Investigation: To discern patterns of hyperalgesias/allodynias
in CRPS I and II and to investigate their pathophysiological natures.
Methods: 132 patients with CRPS I and II underwent neurological
and neurophysiological evaluation following a standard clinical
protocol and conventional nerve conduction, electromyography,
somatosensory evoked potentials, transcranial magnetic stimulation,
quantitative somatosensory thermotest, infrared telethermography,
and placebo-controlled somatic and sympathetic nerve blocks.
Results: Two distinct semeiologic entities surfaced; classic neurological
vs. atypical, fulfilling the description of CRPS II and I respectively.
The CRPS II group (34.9%) exhibited sensory-motor patterns restricted
to the anatomical distribution of nerves and spinal roots and
had evidence of peripheral nerve pathology. The CRPS I group (65.1%)
departed from the laws of anatomy, physiology and pathology. They
had physiological normality of central and peripheral motor and
sensory pathways and abundant psychogenic signs.
Conclusions: These different clinical-physiological characteristics
of hyperalgesias/allodynias signal either psychogenic dysfunction
or structural pathology. These findings question the dictum that
tactile allodynia signals central neuronal sensitization. The
historical argument, when re-examined under evidence-based standards
yields contradiction and gratuitous extrapolation. The refractoriness
of a many neuropathic pain patients to hypothesis-driven, invasive,
or addictive therapy, betrays current misinterpretation of their
authentic neuropathogical and psychopathological origins, while
highlighting the iatrogenic connotation of the present paradigm.
Acknowledgement: Supported NIH grant NS 39761.
Abstract ID: 1211-P127
SKIN BLOOD FLOW CHANGES DURING KETAMINE/MIDAZOLAM ANESTHESIA FOR
A. Ploppa1, R.T. Kiefer1, B. Noh1, P. Rohr2, J. Grothusen3, L.
Distler4, H.J. Dieterich1, K. Unertl1, R.J. Schwartzman3
1 Anesthesiology, Eberhard-Karls University, Tuebingen, Germany
, 2 Anesthesiology, Klinikum Saarbruecken, Saarbruecken, Germany
, 3 Neurology, MCP-Hahnemann University, Philadelphia, PA , 4
Pain Therapy, Caritasklinik St.Theresia, Saarbruecken, Germany
Aim of investigation: To detect and monitor changes in skin blood
flow during experimental high dose ketamine-midazolam anesthesia
for intractable cases of CRPS-I by Laser Doppler Flowmetry (LDF).
Methods: Patients suffering from therapy-refractory CRPS I (duration:
4 months-6 years) received ketamine-midazolam anesthesia over
5 days. Skin perfusion was determined by LDF (Perimed, PF 4100)
on D-II and radial forearm. In one patient with severe allodynia
at the upper arm this area and D-II were measured.
Results:Significantly decreased skin perfusion seems to occur
in late stages with manifest atrophic and dystrophic signs. Under
ketamine anesthesia, a significant increase in skin blood flow
was observed (clinical correlate: hyperemia, edema) in the first
72 hours. Areas of maximal allodynia showed the strongest increase
in blood perfusion (up to ten-fold, p<0.05). The highest increment
in skin blood flow was observed in patients with dystrophy and
atrophy. During the following days, normalization of skin blood
flow and regaining vasomotor activity were observed (clinical
correlate: decrease of swelling, hyperemia, temperature changes).
Conclusions: LDF might be a valid and noninvasive method to monitor
skin perfusion changes and potentially success of therapeutic
procedures for CRPS I. Further evidence is needed to qualify and
quantify regained vasomotive activity as indicator of effective
Abstract ID: 1210-P126
KETAMINE-MIDAZOLAM ANESTHESIA FOR INTRACTABLE COMPLEX REGIONAL
R.T. Kiefer1, P. Rohr2, A. Ploppa1, H.J. Dieterich1, K.H. Altemeyer2,
J. Grothusen3, K. Unertl1, R.J. Schwartzman3
1 Anesthesiology, Eberhard-Karls University, Tuebingen, Germany
, 2 Anesthesiology, Klinikum Saarbruecken, Saarbruecken, Germany
, 3 Neurology, MCP-Hahnemann University, Philadelphia, PA
Aim of Investigation: Sufficient pain relief for Complex Regional
Pain Syndrome Type I (CRPS-I/RSD) remains challenging. Accumulating
evidence points to the involvement of sensitized central pain
projecting neurons by NMDA-receptor activation. This evidence
is the rationale for prolonged NMDA-blockade with ketamine in
intractable CRPS-I patients.
Methods: Six patients with steadily worsening CRPS-I, who failed
all standard medical and sympatholytic treatment, were anesthesized
in the ICU's of hospitals in Tuebingen and Saarbruecken, Germany.
Treatment was initiated by bolus injections of ketamine (0.5mg/kg)
and midazolam (2.5-5mg) until deep sedation (Ramsay Score 4-5)was
reached.Therapy was maintained with infusions of ketamine (3-7mg/kg/h)
and midazolam (0.15-0.3mg/kg/h) over five days. On the fifth day
infusions were slowly tapered. 3 patients did not require intubation
and 3 were pre-emptively intubated (1 for increased aspiration
risk, 2 due to respiratory infection).
Results: Six patients underwent treatment without significant
complications. All showed an excellent immediate response and
were pain free and without spontaneous or touch evoked allodynia
or hyperalgesia. One patient has remained completely pain free
for more than 2 years. Five of the six patients had return of
the pain of the original injury, but are relieved of the hyperalgesia,
mechanical and thermo-allodynia and swelling in the affected areas.
Conclusions: Prolonged ketamine-midazolam anesthesia shows promise
as an effective therapeutic option for severe and otherwise intractable
cases of CRPS-I.