|
INTRODUCTION:
Some of these studies are abstracts and others are review articles
of research studies on RSD/CRPS. Studies are listed alphabetically
according to author. Prominent researchers in the field are listed
also. International Dutch RSD/CRPS Conference 2003 studies by European
doctors and researchers are featured. Studies of note are listed
with *** at beginning.
STUDIES 2005:
To see abstracts presented at the August 2005 International Association
for the Study of Pain (IASP) Conference in Sydney, Australia, or
studies in 2005, click
here.
STUDIES 2004:
Studies A-M
Studies N-Z
STUDIES 2003:
Charles Berde MD PhD
Robert Schwartzman MD
Studies A-M
Studies N-Z
International Dutch RSD Conference:
Nov. 14-15, 2003.
HOT OFF THE PRESS! STUDIES 2004
STUDIES A-M
For a copy of this or any CRPS article,
visit McMaster Health Sciences Library. Search Pub Med using the
PMID number listed.
Backonja MM, Serra
Pharmacologic management part 2: lesser-studied neuropathic
pain diseases.
J.Pain Med. 2004 Mar;5 Suppl 1:S48-59.
University of Wisconsin Hospital and Clinics, Madison, Wisconsin;
Neuropathic Pain Unit, Hospital General de Catalunya, Barcelona,
Spain.
This second part of a review of the pharmacologic management of
neuropathic pain diseases describes the current treatment options
for three lesser-studied neuropathic syndromes: Central post-stroke
pain, spinal cord injury, and complex regional pain syndrome II.
Diagnosis can be difficult in patients with these syndromes, because
the pain experienced is much greater and of a different type than
would normally be expected following a stroke or injury to the spinal
cord or a peripheral nerve. Even when an accurate and timely diagnosis
is made, treatment options are limited and frequently suboptimal.
However, the results of published trials do support the use of anticonvulsants
and/or tricyclic antidepressants as first-line pharmacotherapy in
these three neuropathic pain syndromes. To maximize treatment outcomes,
future research must: Continue to more fully elucidate the relationship
between the signs and symptoms of pain and the underlying pathophysiology;
Delineate the natural history of central post-stroke pain, spinal
cord injury, and complex regional pain syndrome; Identify patient-related
factors that may indicate an increased risk of developing neuropathic
pain following stroke or nerve injury; Investigate emerging treatments
that target underlying pain mechanisms.
PMID: 14996229
***Carter ML.
Spinal cord stimulation in chronic pain: a review of the
evidence.
Anesth Intensive Care. 2004 Feb;32(1):11-21.
Department of Anaesthesia, Bundaberg Base Hospital, PO Box 34,
Bundaberg, Qld 4670.
This review looks at the evidence for the effectiveness of spinal
cord stimulation in various chronic pain states. Spinal cord stimulation
can only be effective when appropriate dorsal column fibres in the
spinal cord are preserved and able to be stimulated. Spinal cord
stimulation has been shown to have little to offer for patients
with some diagnoses. Although 50 to 60% of patients with failed
back surgery syndrome obtain significant pain relief with this technique,
the strength of the evidence available is insufficient to clearly
advocate its use in all patients with this condition. Though limited
in quantity and quality, better evidence exists for its use in neuropathic
pain, complex regional pain syndrome, angina pectoris
and critical limb ischaemia. There is a lack of high quality evidence
relating to spinal cord stimulation due to difficulties in conducting
randomized controlled trials in this area. Serious methodological
problems are encountered in blinding, recruitment and assessment
in nearly all published trials of spinal cord stimulation. Suggestions
regarding appropriate methodologies for trials which would produce
better quality evidence are summarized.
PMID: 15058115
Cordivari C, Misra VP, Catania S, Lees AJ.
New therapeutic indications for botulinum toxins.
Mov Disord. 2004 Mar;19 Suppl 8:S157-61.
Department of Clinical Neurophysiology, The National Hospital for
Neurology and Neurosurgery, Queen Square, London, United Kingdom.
The efficacy of botulinum toxin (BTX) without systemic effects
has led to the rapid development of applications in neuromuscular
disorders, hyperactivity of sudomotor cholinergic-mediated glandular
function, and pain syndromes. The successful use of BTX in conditions
with muscle overactivity, such as dystonia and spasticity, has been
established and new areas in the field of movement disorders such
as tics, tremor, myoclonic jerks, and stuttering has been explored
with satisfactory results. Strategies to temporarily inactivate
muscle function after orthopaedic or neurosurgery have also been
developed. BTX treatment of hyperhidrosis was followed by its application
in other hypersecretory conditions (hyperlacrimation and nasal hypersecretion)
and in excessive drooling. Studies are in progress, aimed at optimising
the technique and protocol of administration. Other applications
for BTX have been proposed in gastroenterological and urogenital
practice; it appears to be effective in replacing standard surgical
procedures. Trials of BTX in painful conditions are ongoing mainly
on refractory tension headache, migraine, and backache as well as
dystonia-complex regional pain syndrome and myofascial
pain with promising results. Recently, the fastest growing use for
BTX toxin has been in the cosmetic applications. Clearly, the indications
for the use of BTX are expanding, but further clinical trials will
be needed in many different areas. Copyright 2004 Movement Disorder
Society
PMID: 15027069
Drummond PD, Finch PM.
Persistence of pain induced by startle and forehead cooling
after sympathetic blockade in patients with complex regional pain
syndrome.
J Neurol Neurosurg Psychiatry. 2004 Jan;75(1):98-102
School of Psychology, Murdoch University, Perth, Western Australia,
Australia.
BACKGROUND: Stimuli arousing sympathetic activity can increase
ratings of clinical pain in patients with complex regional pain
syndrome (CRPS). OBJECTIVE: To determine whether the increase in
pain is mediated by peripheral sympathetic activity. METHODS: The
effect of sympathetic ganglion blockade on pain evoked by a startle
stimulus and cooling the forehead was investigated in 36 CRPS patients.
RESULTS: Loss of vasoconstrictor reflexes and warming of the limb
indicated that sympathetic blockade was effective in 26 cases. Before
sympathetic blockade, pain increased in 12 of these 26 patients
when they were startled. Pain increased in seven of the 12 patients
and in another five cases when their forehead was cooled. As expected,
pain that increased during sympathetic arousal generally subsided
in patients with signs of sympathetic blockade. However, pain still
increased in three of 12 of patients after the startle stimulus
and in six of 12 of patients during forehead cooling, despite indisputable
sympathetic blockade. CONCLUSIONS: These findings suggest
that stimuli arousing sympathetic activity act by a central process
to exacerbate pain in some patients, independent of the peripheral
sympathetic nervous system. This may account for the lack of effect
of peripheral sympathetic blockade on pain in some CRPS patients.
PMID: 14707316
Forouzanfar T, Kemler MA, Weber WE, Kessels AG, van Kleef M.
Spinal cord stimulation in complex regional pain syndrome:
cervical and lumbar devices are comparably effective.
Br J Anesth 2004 Mar;92(3):348-53. Epub 2004 Jan 22.
Department of Anaesthesiology, University Hospital Maastricht,
Maastricht, The Netherlands.
BACKGROUND: Spinal cord stimulation (SCS) has been used since 1967
for the treatment of patients with chronic pain. However, long-term
effects of this treatment have not been reported. The present study
investigated the long-term effects of cervical and lumbar SCS in
patients with complex regional pain syndrome type I.
METHODS: Thirty-six patients with a definitive implant were included
in this study. A pain diary was obtained from all patients before
treatment and 6 months and 1 and 2 years after implantation. All
patients were asked to complete a seven-point Global Perceived Effect
(GPE) scale and the Euroqol-5D (EQ-5D) at each post-implant assessment
point. RESULTS: The pain intensity was reduced at 6 months, 1 and
2 years after implantation (P<0.05). However, the repeated measures
ANOVA showed a statistically significant, linear increase in the
visual analogue scale score (P=0.03). According to the GPE, at least
42% of the cervical SCS patients and 47% of the lumbar SCS patients
reported at least 'much improvement'. The health status of the patients,
as measured on the EQ-5D, was improved after treatment (P<0.05).
This improvement was noted both from the social and from the patients'
perspective. Complications and adverse effects occurred in 64% of
the patients and consisted mainly of technical defects. There were
no differences between cervical and lumbar groups with regard to
outcome measures. CONCLUSION: SCS reduced the pain intensity and
improves health status in the majority of the CRPS I patients in
this study. There was no difference in pain relief and complications
between cervical and lumbar SCS.
PMID: 14742334
Gorodkin R, Moore T, Herrick A.
Assessment of endothelial function in complex regional
pain syndrome type I using iontophoresis and laser Doppler imaging.
Rheumatology (Oxford). 2004 Mar 16
University of Manchester Rheumatic Disease Centre, Hope Hospital,
Salford, UK.
OBJECTIVES: To assess microvascular endothelial function in patients
with complex regional pain syndrome type I (CRPS)
compared with healthy controls, as measured by iontophoresis of
vasoactive chemicals and laser Doppler imaging. METHODS: Microvascular
blood flow was stimulated locally in affected and contralateral
limbs of patients with CRPS (n = 17) and in control subjects (n
= 16) using iontophoresis of the endothelial-dependent vasodilator
acetylcholine (ACh) and the endothelial-independent vasodilator
sodium nitroprusside (NaNP). Changes in blood flow were measured
using laser Doppler imaging. Comparisons were made between right
and left limbs and between patients and controls. RESULTS: No significant
differences in blood flow [expressed as a median percentage increase
from baseline (interquartile range)] were detected between affected
and contralateral limbs in patients with CRPS for ACh [affected
237 (95-344); unaffected 251 (152-273)] or for NaNP [affected 102
(49-300); unaffected 190 (53-218)]. In addition, there were no significant
differences between patients and healthy controls [controls, ACh
216 (119-316); controls, NaNP: 122 (48-249)]. CONCLUSIONS: In this
pilot study, CRPS was not associated with impairment of microvascular
endothelial function. This may be a true result or may reflect the
diversity of the CRPS disease process.
PMID: 15026582
Clark, Triesman GJ Pain and Depression An Interdisciplinary Patient-Centered
Approach Adv Psychosom Basel Karger 2004 Vol. 25 pp 89-101
Grabow T, MD Raja, MD S Christo, P.
CRPS: Diagnostic Controversies, Psychological Dysfunction
and Emerging Concepts
Division of Pain Medicine, Dept. of Anesthesia and Critical Care
Medicine, Johns Hopkins University School of Medicine, Baltimore
MD USA
ABSTRACT: Complex regional pain syndrome types I and II are neuropathic
pain disorders that involve dysfunction of the peripheral and central
nervous system. CRPS type I and II are formerly known as reflex
sympathetic dystrophy and causalgia, respectively. Most experts
believe that a multidisciplinary approach including pharmacotherapy,
physiotherapy, and psychotherapy is warranted. Historically, there
has been considerable controversy regarding this disease entity.
In particular, the precise mechanism of the sympathetic dysfunction
as well as the nature of the psychological dysfunction commonly
observed in patients with CRPS has been the subject of considerable
debate. Current strides in our understanding of the pathophysiology
of this disease have improved treatment options.
Introduction
Complex regional pain syndrome (CRPS) types I and II formerly known
as reflex sympathetic dystrophy and causalgia, are neuropathic pain
disorders likely involving dysfunction of the both the peripheral
and central nervous system. The pathophysiology is poorly understood
and treatments often are directed at managing signs and symptoms
of the disease. A significant number of patients exhibit comorbid
psychological dysfunction which has led some clinicians to believe
incorrectly that it is entirely a psychiatric disease. Animal research
has improved our mechanistic understanding of neuropathic pain and
this awareness hay facilitate our understanding of CRPS (particularly
type II). Recent clinical investigation has resulted in an improved
understanding of the biological dysfunction observed in patients
with CRPS. This review will (1) summarize the historical arguments
and controversy surrounding the disease, (2) describe the psychological
dysfunction often observed in patients with CRPS and (3) discuss
recent trends in the neurobiological understanding of CRPS.
CRPS Controversy and Misunderstanding
CRPS History
Several authors have questioned the validity of CRPS type I as an
actual organically based neurological disease and have doubted the
involvement of the sympathetic nervous system in the maintenance
of the pain. Many aspects of the disease, including nomenclature,
etiopathogenesis, diagnosis and treatment have generated considerable
controversy. As a result, CRPS type I (RSD), has been considered
by some experts an expression of somatoform disease and therefore
has been designated as pseudoneuropathy of psychogenic origin. A
brief discussion of several of these arguments is warranted.
Nomenclature
Causalgia was first described in 1864 as a distinct disease entity
by Silas Weir Mitchell who noted extreme pain, autonomic abnormalities,
trophic changes and involuntary movements in Civil War soldiers
who suffered from traumatic injury to peripheral nerves.
Renee Leriche later postulated in 1916 that the sympathetic nervous
system was involved in pain states involving major tissue or nerve
injury, the term RSD was coined nearly half a century later in 1946
by JA Evans to describe patients who exhibited causalgia-like symptoms
but without evidence of major tissue or nerve injury. Several other
terms have been used to describe this disease such as minor causalgia,
algodystrophy, shoulder-hand syndrome, posttraumatic dystrophy,
and Sudeck’s atrophy. In general, the disease was given different
names based on the personal assumptions, frame of reference, institutional
background, or country of origin of the investigators who were describing
the disease process.
In 1994, a task force commissioned by the IASP introduced the present
day descriptive terminology to standardize the nomenclature, remove
obsolete mechanistic understandings, and improve disease recognition,
Until this time, scholars had argued that the term RSD erroneously
implied an underlying “reflexive” mechanism presumably
related to aberrant function (ex. hyperactivity) of the sympathetic
nervous system that if left untreated, would inevitably lead to
permanent dystrophic change. Today, most authorities recognize that
sympathetic (overactivity) is not observed and that sympathetic
dysfunction and dystrophic changes occur only in a subset of patients
with CRSP. Furthermore, certain therapies specifically aimed at
the sympathetic nervous system may be unwarranted. (1,2). Despite
the efforts of the IASP, many clinicians are unfamiliar with the
modern taxonomy and the majority of contemporary investigations
fail to utilize the diagnostic criteria proposed by the IASP.
Diagnosis
According to the IASP, the diagnosis of CRPS requires (1) an initiating
noxious event or cause of immobilization (2) continuing pain, allodynia
or hyperaglesia disproportionate to any inciting event (3) evidence
at some time of edema, changes in skin blood flow, or abnormal sudomotor
activity and (4) the exclusion of a medical condition that would
otherwise account for the degree of pain and dysfunction. the presence
on an initiating noxious event or cause of immobilization was not
required according to the original publication by the IASP in 1994;
however, this statement was omitted from the more widely available
and Meddling-indexed summary statement from the consensus meeting
published in 1995.. Importantly, a precipitating inciting event
may not be detected in approximately 10% of patients with CRPS(6).
This definition is entirely descriptive and does not imply etiology
or specific pathophysiology. This lack of mechanism based specificity
in the proposed diagnostic criteria has detracted somewhat from
its universal acceptance by the scientific community.
Etiopathogenesis
Patients with CRPS exhibit signs of emotional duress and psychological
dysfunction. Consequently, it was tempting for early investigators
to conclude that much of the pain and symptomatology was the results
of untreated psychiatric disease or caused by exaggerated sympathoarousal
secondary to underlying stress. The term RSD helped to maintain
this cause and effect link between the sympathetic nervous system,
and the pain. As a result, many patients underwent therapies designed
to mitigate sympathetic nervous system dysfunction. Today there
is convincing evidence in animals and humans that nerve injury and
tissue inflammation may be associated with aberrant functioning
of the sympathetic nervous system. (7) (Table 1) Despite this link,
the pathophysiology of CRPS is incompletely understood and several
mechanisms may be operating simultaneously. Furthermore, it is commonly
recognized that only a subset of patients with CRPS have sympathetically
maintained pain ((SMP) which is defined as pain that is modulated
by sympathetic block or pharmacological antagonism of alpha adrenoreceptor
function.
Psychological Dysfunction
Psychiatric Comorbid Conditions in Chronic Pain
Chronic pain patients frequently have associated comorbid psychiatric
disease.(8). When ranked form most frequent to least frequent, the
following comorbid conditions likely are associated more with chronic
pain patients than with the general population: affective disorders
(depression), psychoactive substance, use-related disorders, somatoform
disorders, and anxiety disorders. Moreover, a significant number
of chronic pain patients may have more than one axis I psychiatric
comorbidity. Psychiatric comorbidities can have a negative impact
on chronic pain and functional status. In addition, there are a
group of conditions commonly observed in chronic pain patients that
are not necessarily psychiatric in nature which in addition, do
not satisfy formal Diagnostic and Statistical Manual (DSM) criteria.
These observations include such things as pain behaviours, sleep
disturbance, somatization, nonorganic physical findings, and impaired
functional status out of proportion to physician expectations based
on objective findings(8). The prognostic implication of these conditions
is unknown.
Psychiatric Disease in CRPS
Patients with CRPS commonly suffer from psychological dysfunction.
In fact, patients with CRPS experience a significant amount of depression,
anxiety and phobia. However, attempts to establish a unique “CRPS
personality” have been unsuccessful. In general, early studies
lacked validity due to various flaws in methodological design. For
example, studies failed to examine premorbid personality data, investigators
used heterogenous definitions of psychiatric terminology and psychometric
instruments had nor been normed on pain populations(9). Nevertheless,
reported prevalence of psychiatric disorders in patient with CRPS
ranges from 18-64%(10). Psychological examination using the Structured
Clinical Interview (SCID) of the DSM-IV demonstrates a high frequency
of affective disorder (46%), anxiety disorder (27%), and substance
abuse disorder (14%) in patients with CRPS.(11). However, the prevalence
of psychiatric disorders in patients with CRPS may not be much different
from chronic pain patients in general. For example, the prevalence
of major depression (1.5-54.5%), anxiety disorders (7-62.5%) and
substance abuse disorders (3.2-18.9%).in chronic pain patients is
reported in similar rates as CRPS patients (8) Finally Breuhl and
Carlson (10) reviewed data strictly from studies which used the
MMPI and concluded that patients with CRPS like patients with chronic
pain in general, are somatically preoccupied, depressed and use
repression as a psychological defense mechanism.
There has been historical debate whether chronic pain or psychiatric
illness is the primary process. The reciprocal relationship between
pain and psychological dysfunction in patient with CRPS is evident
from a recent study of daily diaries which demonstrated that yesterday’s
depressed pain also contributed to today’s depression, anxiety
and anger.(12)> Several literature reviews have examined whether
psychological dysfunction was the cause or effect of CRPS. (9,10,13).
In general, the majority of historical studies suffered from flaws
in methodology such as lack of consistent and homogenous diagnostic
groups, lack of control groups and significant statistical tests,
lack of objective measures of psychological disease, poorly defended
behavioural criteria, and incorrect use of psychiatric or psychological
terminology(13). As a result, Lynch (13) concluded there is no valid
evidence that certain personality traits or psychological factors
predispose one to the development of CRPS. Similarly, due to the
methodological weakness of the literature, Breuhl and Carlson (10)
concluded that there is insufficient data to draw meaningful conclusions
whether or not pre-existing psychological factors predispose to
the development of CRPS.
In summary, most authors have concluded that cormorbid psychological
disease in patients with CRPS is a consequence of the chronic pain
rather than its cause. (9, 13). Further more, there is no evidence
that individuals with certain personality types are predisposed
to developing CRPS. Finally there are no consistent psychological
differences between CRPS and non-CRPS pain patients (14-22).
Table 2)
Factitious Disorder
The overall prevalence of factitious disorder in chronic pain patients
is between 0,14 and 2% (8). Patients with conversion disorder and
factitious illness my have similar clinical presentation to patients
with CRPS. In Fact, certain sensory sign (ex. Non-anatomical and
expansive areas of hypoesthesia or hyperalgesia with normal peripheral
sensory nerve conduction of somatosensory evoked potentials) or
features (e.g. normalization of hypoesthesia by nerve blocks) identified
in patients with CRPS type 1 likely are psychogenic in origin. Moreover,
neurophysiological investigation suggest that certain positive motor
signs (dystonia, tremors, spasms, irregular jerks) identified in
patients with CRPS type I are in fact psychogenic in origin and
represent psuedoneurological illness(23).
Strain and Distress in Caregivers
Caregivers of patients with CRPS experience significant levels
of strain and susceptibility to depression measured by the Caregiver
Strain Index (CSI) and General Health Questionnaore012 (GHQ 12),
respectively(24). Caregiver health can have a significant impact
on recipient care. Thus, physicians should not only implement psychosocial
interventions directed at patients but also caregivers of patient
with CRPS.
Other Issues (Legal, Disability)
Allen et al (25) recently performed a retrospective chart review
of the epidemiology of CRPS. They reported that 54% of patients
had a worker compensation claim and that 17% had a lawsuit related
to the CRPS. The effect of litigation on pain severity and clinical
outcomes for patients with CRPS is unknown.
Neglect-like Symptoms
Patients with CRPS often display signs of motor dysfunction that
appear to be related to voluntary guarding in order to avoid exacerbation
of pain. However, recent evidence suggest that motor dysfunction
may be related to neglect-like symptoms ( e.g. cognitive neglect,
motor neglect)in a subset of patients with CRPS(26.) Of note, self-reported
motor dysfunction is the second most commonly reported groups of
symptoms after sensory dysfunction in patient with CRPS. (27).
Quality of Life
A pilot study demonstrated substantial interference with quality
of like measured by modified Brief Pain Inventory (mBPI) as well
as significant sleep disturbance in patient with CRPS(27).
Stressful Life Events
Stressful life events were more common in patients with CRPS than
in a control group of patients with hand pathology measured by the
Social Readjustment Rating Scale (SRRS) (20). However, these authors
concluded that there was no direct casual relationship between these
stressful life events or any underlying psychological dysfunction
measured by SCL-90 and the onset of CRPS. In a retrospective study,
Geertzen et al (28) concluded that stressful life events and psychological
dysfunction measured by the SRRS and RAND-36 item health Survey
(RAND-36), respectively, already existed at the time of diagnosis
of CRPS and did not results from CRPS.
RECENT TRENDS
Sympathetic Nervous System
In animals, there is overwhelming evidence that nerve injury and
inflammation can result in functional coupling between the sympathetic
efferents and primary sensory afferent neurons within the peripheral
nervous system (7).The site of this aberrant sympathetic-sensory
coupling involves the dorsal root ganglia (DRG) the area of injury
itself (e.g. neuroma site) or within the tissue innervated by the
injured nerve.
Several of these correlates exist in humans and these findings have
been summarized in recent reviews (7). For example, peripheral nerve
injury results in sympathetic sprouting and functional coupling
between sympathetic efferents and primary sensory afferent neurons
in the DRG (29). An increase of alpha-adrenoreceptors have been
observed in the hyperalgesic skin of patients with CRPS type 1 (30).
Patients with CRPS I have decreased sympathetic outflow but increased
?-adrenergic responsiveness in the affected limbs suggesting adrenergic
supersensitivity. This supersensitivity is reversed with CRPS symptoms
resolve. Pharmacological or surgical sympathectomy can decrease
pain in patient with CRPS and patients with neuropathic pain report
increased pain during stress or after intradermal injection of a
physiological dose of norepinephrine(NE)(31). In addition, injections
of NE can rekindle pain and mechanical hyperalgesia in patient who
have had a previous sympathetic block. Finally, inflammatory pain
and hyperalgesia produced by topical capsaicin is decreased by a-adrenoceptor
antagonists and increased by NE(32).
Despite this evidence, systematic reviews have failed to demonstrate
the efficacy of therapies designed to inhibit sympathetic function
and question their unity (1,2).In fact, some investigators have
challenged the validity of pharmacological tests to establish the
diagnosis of SMP. The pain can be challenging even for clinicians
with considerable expertise. (33).
Recent studies have examined the effect of the natural stimulation
of the subject’s own sympathetic nervous system on spontaneous
pain and hyperalgesia rather than the effect of pharmacological
treatment such as sympathetic blocks or injections of NE. Sympathetic
arousal increased pain and vasoconstriction in the affected extremity
of patients with CRPS I and II. (34). Also sympathetic activation
increased spontaneous pain and spatial distribution of mechanical
hyperalgesia in patients with CRPS I who have SMP. (34). These two
investigations were the first to demonstrate that physiological
activation of the sympathetic nervous system can modulate the pain
experience in humans through endogenous release of NE from sympathetic
nerve endings. These findings provide evidence in support of the
concept of SMP or pain as the result of sympathetic efferent activity.
SYMPATHETIC NERVOUS SYSTEM (SNS) DYSFUNCTION
In the acute stage of CRPS I there is complete functional loss
of cutaneous sympathetic vasoconstrictor activity as well as decreased
venous plasma levels of NE (presumably secondary to decreased postganglionic
release from sympathetic terminals) confined to the affected extremity
(36). This autonomic impairment may recover within weeks and likely
reflects dysfunction within the CNS. During chronic CPRS sympathetic
vasoconstrictor neurons are still inhibited but adrenoreceptor supersensitive
in vascular tissue results in ongoing vasoconstriction and subsequent
cold skin. These vascular abnormalities are dynamic and more pronounced
when examined over the entire range of the thermoregulatory cycle
(37).
Patients with acute CRPS I also demonstrate a-adrenergic super sensitivity
of sudomotor nerves that is reversible with disease progression
(38). Unilateral disturbances in sudomotor function determined by
quantitative sudomotor axon reflex test (QSART) and thermoregulatory
sweat test (TST) also have been reported in patients with chronic
CRPS (39).
Sensory Dysfunction
Sensory disturbances are common in patients with CRPS I and II and
predominately consist of hyperalgesia, allodynia, and spontaneous
pain (6). Quantitative sensory testing (QSART) demonstrates an increase
in warm perception thresholds and a decrease of cold pain thresholds
in patient with CRPS I and II. Sensory impairments frequently extend
beyond the affected area and may involve quadratic or hemilateral
regions of the body (41).
Motor Dysfunction
Motor disturbances are prevalent in patients with CRPS I and II.(6)
and are independent of sensory and autonomic complaints (40). The
most frequently described motor disturbance is loss of function
of the affected extremity. Detailed neurological examination may
detect objective evidence of isolated motor weakness, muscle atrophy,
tremor, dystonia, or ataxia. Furthermore, electrodiagnostic and
nerve conduction velocity can be used to document muscle and large
fiber abnormalities, respectively. Decrease in active range of motion
can be assessed by goniometer. Similarly, muscle power can be assessed
by measuring grip force strength or by manual muscle testing. More
complex motor tasks can be measured by kinematic analysis. A recent
study has demonstrated neurophysiological evidence of impairment
of central sensor motor integration in patients with CRPS I (42).
These motor deficits may be secondary to abnormal integration of
visual and sensory inputs to the parietal cortex (43).
CNS Dysfunction
Evidence suggests that certain autonomic, motor and sensory disturbances
in patients with CRPS are caused by dysfunction within the CNS whereas
certain aspects of the pain itself may be related to aberrant peripheral
mechanisms. Potential peripheral and central mechanisms are described
elsewhere (7,44). Occasionally, dysfunction of the sensory, motor,
or autonomic nervous system, may involve bilateral structures after
unilateral nerve or tissue injury (45). In addition, several investigators
have described CNS abnormalities by fMRI, MRS, or SPECT. Recent
investigation suggests that patients with CRPS may develop function
or structural reorganization and change in central representation
of sensory maps. However it is unclear whether these abnormalities
are as a result of the chronic pain or whether they represent specific
regions of primary dysfunction within the CNS.
Treatment Algorithm for CRPS
The therapeutic strategy for patients with CRPS involves the concurrent
utilization of pharmaoco-,physio- and psychotherapy. However, randomized
controlled trials (RCT) investigating the impact of psychological
intervention on homogenous groups of patient with neuropathic pain,
including patients with CRPS have not been undertaken (46) Nevertheless,
principles derived from operant and cognitive behaviour theory are
useful to treat chronic pain patient in general and these strategies
should be used for patients with CRPS. The goal of pharmacological
therapy is to reduce pain in order to facilitate functional restoration.
In general medications that are effective for the treatment of neuropathic
pain are used for patients with CRPS. The goal of physiotherapy
is to improve functional status. In general desensitization and
physical rehabilitation cannot proceed without adequate pain control.
Most authorities believe that active participation in physical therapy
is instrumental for improvement in patient with CRPS. To date, only
the short term efficacy of physical therapy has been demonstrated
by a RCT specifically for CRPS patients (47). The use of these interventional
techniques should be considered in the treatment algorithm when
other therapies have failed. A summary of current therapeutic strategies
has been published. (48).
Low doses of a common intravenous anesthetic may relieve
debilitating pain syndrome
Harbut R MD
23 Sep 2004
Limited, low-dose infusions of a widely used anesthetic drug may
relieve the often intolerable and debilitating pain of Complex Regional
Pain Syndrome (CRPS), a Penn State Milton S. Hershey Medical Center
researcher found.
"This pain disorder is very difficult to treat. Currently-available
therapies, at best, oftentimes only make the pain bearable for many
CRPS sufferers," said Ronald E. Harbut, M.D., Ph.D., assistant
professor of anesthesiology, Penn State Hershey Medical Center.
"In our retrospective study, some patients who underwent a
low-dose infusion of ketamine experienced complete relief from their
pain, suggesting that this therapy may be an option for some patients
with intolerable CRPS."
The study, titled "Subanesthetic
Ketamine Infusion Therapy: A Retrospective Analysis of a Novel Therapeutic
Approach to Complex Regional Pain Syndrome," was published
in the September 2004 issue of Pain Medicine, the official journal
of the American Academy of Pain Medicine.
CRPS (type I), also known as Reflex Sympathetic Dystrophy Syndrome
(RSD), affects between 1.5 million and 7 million people in the United
States and is oftentimes marked by a severe, burning pain that can
be very resistant to conventional therapies. The pain frequently
begins after a fall or sprain, a fracture, infections, surgery,
or trauma. Often present in the limbs with possible later spreading
to other parts of the body, patients also may experience skin color
changes, sweating abnormalities, tissue swelling, and an extreme
sensitivity to light touch or vibrations. The McGill Pain Index
rates CRPS as 42 on the scale of 50, with 50 being most severe.
Although much is unknown about CRPS, the pain experienced by patients
appears to be caused by over-stimulation of a nerve receptor complex
involved in the process of feeling pain. Therefore, efforts have
been made to treat CRPS by blocking these receptors. Whereas most
pain medications do not effectively block these receptor complexes
(often referred to as NMDA-receptors), ketamine does.
The study was initiated by Graeme E. Correll, B.E., M.B.B.S., and
involved reviewing the medical records of 33 patients with CRPS
treated by Correll. The patients, some of whom had failed to obtain
pain relief from conventional therapies, were treated with low-dose
inpatient intravenous infusions of ketamine between 1996 and 2002
in Mackay, Queensland, Australia. Ketamine infusions were started
at very low rates and were slowly increased in small increments
as tolerated by selected patients. The therapy was then continued
as long as the patient tolerated the drug and continued to benefit
from it. Treatment cycles generally continued until the patient
experienced complete pain relief; until initially-obtained relief
would not improve any further; or for no more than 48 hours if there
was no improvement in pain severity.
Pain was completely relieved for 25 (76 percent) patients, partially
relieved for six (18 percent) patients, and not relieved for two
(6 percent) patients. Although the relief obtained did not last
indefinitely, 54 percent remained completely pain-free for three
months or more and 31 percent for six months or more. For 12 patients
who received a second treatment, 58 percent experienced relief for
one year or more with 33 percent remaining pain-free for more than
three years.
The most frequent side effect reported was a feeling of inebriation.
Hallucinations occurred in six patients with less frequent side
effects including complaints of light-headedness, dizziness and
nausea. Liver enzymes were altered in four patients but resolved
after therapy.
The exact mechanism of sustained pain relief is unknown, but is
currently under study at Penn State Hershey Medical Center. Harbut
likened the ketamine treatment to the healing of a broken bone.
"If someone breaks a bone and you simply put the two pieces
back together, they won't immediately heal. However, if you add
a splint and hold the bones steady for a period of time, and then
later take away the splint the bone is healed. I believe that the
ketamine treatment does something similar that lends support and
allows the nerve cells to heal themselves, so that when you take
away the ketamine, the pain is reduced or gone."
Harbut began studying CRPS with Correll during a work assignment
Harbut volunteered to take in far northern Queensland, Australia,
in the late 1990s. Correll was developing a therapy for CRPS but
wanted a collaborator to formally research the effectiveness of
the therapy. Harbut brought Correll's method back to the U.S. where
he developed an FDA-approved study protocol (used at the Mayo Clinic
Scottsdale) using this method to attempt to treat post herpetic
neuralgia, another pain disorder with symptoms somewhat similar
to CRPS. At the same time, Harbut met a patient who had suffered
with intolerable CRPS for nine years who wanted to try this new
therapy. That patient became the first successful treatment of intractable
CRPS in the U.S. (A Case Report of this treatment appeared in the
June 2002 issue of Pain Medicine.)
"Ultimately, we want to find a way to improve the quality
of life for those who suffer with intolerable CRPS, some of whom
at times contemplate suicide because of their endless pain,"
Harbut said. "Although optimistic about these early findings,
certainly more study is needed to further establish the safety and
efficacy of this novel approach." (A large clinical study is
currently planned and under development at Penn State Hershey Medical
Center.)
In addition to Harbut and Correll, the team involved in this study
included: Jahangir Maleki, M.D., Ph.D., and Edward J. Gracely, Ph.D.,
Drexel University College of Medicine; and Jesse J. Muir, M.D.,
Mayo Clinic Scottsdale.
***Huygen FJ, Ramdhani N, Van Toorenenbergen A, Klein J, Zijlstra
FJ.
Mast cells are involved in inflammatory reactions during
Complex Regional Pain Syndrome type 1.
Immunol Lett. 2004 Feb 15;91(2-3):147-154.
Pain Treatment Center, Department of Anesthesiology, P.O. Box
2040, 3000 CA Rotterdam, The Netherlands.
Background: The Complex Regional Pain Syndrome type 1 (CRPS1) is
a complication of surgery or trauma but spontaneous development
is also described. Although the pathogenesis remains debatable,
afferent, efferent and central nervous system mechanisms are proposed.
Recently we showed involvement of the proinflammatory cytokines
IL-6 and TNFalpha which is direct evidence for an inflammatory process.
Many types of cells, such as activated T lymphocytes, monocytes,macrophages
and skin resident cells like mast cells, could contribute to the
production of cytokines. Involvement of mast cells is relatively
easy to detect by measurement of tryptase. Aim: To establish whether
mast cells are involved in the inflammatory reactions during CRPS1.
Methods: Twenty patients fulfilling the Bruehl criteria with CRPS1
in one extremity were studied. Impairment was assessed by registration
of pain and measurement of differences in temperature, volume and
mobility between the involved and uninvolved extremity. Blisters
were made with a suction method in order to determine cytokines
and mast cell derived tryptase in the involved and uninvolved extremity.
Results: In the blister fluid a significant difference ( [Formula:
see text] range, Wilcoxon signed-ranks test [Formula: see text]
) was found between the involved and uninvolved extremity in IL-6
{53.5 (17.3-225) versus 6.2 (2-20.3) pg/ml}, TNFalpha {31 (15.5-131.5)
versus 8 (4-39) pg/ml}, and tryptase {37 (20.5-62.3) versus 12.5
(6.7-23.5)ng/ml}. There was a significant correlation (0.455) between
the intensity of pain and tryptase levels in the involved extremity
(Spearman's test, [Formula: see text] ). Conclusion: Mast
cells are involved in inflammatory reactions during the CRPS1. Mast
cells could play a role in the production of cytokines such as TNFalpha.
PMID: 15019283
______________________
***Huygen FJ, Niehof S, Klein J, Zijlstra FJ.
Computer-assisted skin videothermography is a highly sensitive
quality tool in the diagnosis and monitoring of complex regional
pain syndrome type I.
Eur J Appl Physiol. 2004 Jan 21
Department of Anesthesiology, Pain Treatment Centre, Erasmus MC,
P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
The use of thermography in the diagnosis and evaluation of complex
regional pain syndrome type 1 (CRPS1) is based on the presence of
temperature asymmetries between the involved area of the extremity
and the corresponding area of the uninvolved extremity. The interpretation
of thermographic images is, however, subjective and not validated
for routine use. The objective of the present study was to develop
a sensitive, specific and reproducible arithmetical model as the
result of computer-assisted infrared thermography in patients with
early stage CRPS1 in one hand. Eighteen patients with CRPS1 on one
hand and 13 healthy volunteers were included in the study. The severity
of the disease was determined by means of pain questionnaires [visual
analogue scale (VAS) pain and McGill Pain Questionnaire], measurements
of mobility (active range of motion) and oedema volume. Asymmetry
between the involved and the uninvolved extremities was calculated
by means of the asymmetry factor, the ratio and the average temperature
differences. The discrimination power of the three methods was determined
by the receiver-operating curve (ROC). The regression between the
determined temperature distributions of both extremities was plotted.
Subsequently the correlation of the data was calculated. In normal
healthy individuals the asymmetry factor was 0.91 (0.01) (SD), whereas
in CRPS1 patients this factor was 0.45 (0.07) (SD). The performance
of the arithmetic model based on the ROC curve was excellent. The
area under the curve was 0.97, the P value was <0.001, the sensitivity
92% and specificity 94%. Furthermore, the temperature asymmetry
factor was correlated with the duration of the disease and VAS pain.
In conclusion, in resting condition, videothermography is
a reliable additive diagnostic tool of early stage CRPS1. This objective
tool could be used for monitoring purposes during experimental therapeutic
intervention.
PMID: 14735366
Karacan I, Aydin T, Ozaras N.
Bone loss in the contralateral asymptomatic hand in patients
with complex regional pain syndrome type 1.
Metab. 20 J Bone Miner 04;22(1):44-7.
SSK Vakif Gureba Hospital Physical Medicine and Rehabilitation Clinic,
Istanbul, Turkey.
Regional osteoporosis was seen radiographically in clinically affected
areas in patients with complex regional pain syndrome type 1 (CRPS1).
The aim of the this study was to investigate whether bone loss developed
in the contralateral hand in patients with unilateral CRPS1 of the
hand. Thirty-two patients with CRPS1 of the hand were included in
this study. Bone mineral density was measured in the left proximal
femur and both ultradistal radiuses, using dual-energy X-ray absorptiometry.
The subjects were classified as grades 1 to 3 according to the T-score
of both ultradistal radiuses (densitometric grades): grade 1, both
radiuses were normal; grade 2, bone loss was determined only in
the affected radius; and grade 3, there was bone loss in both radiuses.
Twenty (62.5%) patients had bone loss in the affected hand; 11 patients
(34.4%) had bone loss only on the affected side and 9 patients (28.1%)
had bone loss on both sides. The mean duration of the period between
the diagnosis of the injury and the measurement of bone density
was 1.9 +/- 0.6 months in patients with grade 1, 3.1 +/- 1.0 months
in patients with grade 2, and 5.5 +/- 2.2 months in patients with
grade 3. The Spearman test showed a significant correlation between
the period of injury and the densitometric grade ( R = 0.774; P
= 0.0001). In conclusion, the current study of patients with CRPS1,
showed that the bone loss in the asymptomatic contralateral hand
developed at a later stage than that in the affected hand. This
bone loss was less frequent and of a lower degree in the asymptomatic
contralateral hand than in the affected hand. The bone loss in the
asymptomatic contralateral hand could be explained by the loss of
sympathetic tone in CRPS1 and contralateral sympathetic innervation.
PMID: 14691686
Lake AP.
Intravenous regional sympathetic block: past, present and
future?
Pain Res Manag. 2004 Spring;9(1):35-7.
Glan Clwyd Hospital, Bodelwyddan, Denbighshire, United Kingdom.
Intravenous regional sympathetic block is a valued component of
the pain clinician's armamentarium for the management of the complex
regional pain syndrome type 1. Treatment of this multifaceted condition
is multimodal, and despite a lack of convincing supporting evidence
from clinical trials, the author makes the case for retaining the
technique while recommending both appropriate guidance and further
study.
PMID: 15007401
Mense S.
Neurobiological basis for the use of botulinum toxin in
pain therapy.
J Neurol. 2004 Feb;251 Suppl 1:1-7.
Institut fur Anatomie und Zellbiologie III, Universitat Heidelberg,
Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
The various serotypes of botulinum toxin (BoNT) exert their action
by inhibiting the exocytosis of acetylcholine (ACh) on cholinergic
nerve endings. BoNT cleaves proteins (e.g. SNAP-25 or VAMP) that
are necessary for the docking of the ACh vesicle to the presynaptic
membrane. Without docking, no ACh can be released into the synaptic
cleft and the innervated structure is paralyzed. This article focuses
on the neuromuscular endplate. The main targets of BoNT therapy
are states of muscle hyperactivity such as contractures (in the
physiological sense), or spasm and focal dystonias. CONTRACTURES:
The "integrated hypothesis" of the formation of myofascial
trigger points suggests that a lesion of a muscle damages the endplate
so that excessive ACh is released. This causes a local contracture
(partial contraction of a muscle fiber) underneath the endplate.
The contracture compresses small blood vessels, and the tissue becomes
ischemic. Ischemia leads to the release of bradykinin (BKN) and
sensitization or excitation of nociceptors. BoNT is a causal therapy
in these cases, because it stops the excessive ACh release. SPASM:
Reflex spasm in a given muscle can be induced by nociceptive input
from neighboring joints or muscles. If the force generated by a
spasm is relatively high, it will compress the large blood vessels
supplying the muscle. The final effect again is ischemia. In this
case a drop in pH may accompany the ischemia and BKN are known to
be effective stimulants for muscle nociceptors. DYSTONIA: In cases
of weak dystonias, a compression of blood vessels is unlikely. However,
the tonic contraction will cause a lowering of pH and a release
of ATP. Muscle cells contain ATP at concentrations sufficient to
excite muscle nociceptors. In cases of spasm and dystonia, BoNT
can abolish the pain by relaxing the muscle. Since many patients
report alleviation of their pain before the muscle relaxing effect
of BoNT has set in, a direct analgesic action of BoNT is being discussed.
Most hypotheses rest on the assumption that BoNT inhibits not only
the exocytosis of ACh but also of their neurotransmitters. Such
an action could be analgesic if the release of neuropeptides from
nociceptive nerve endings is prevented. This way, BoNT could alleviate
the pain of neuropathies and various types of headache where neurogenic
inflammation plays a role. Another site of an analgesic action could
be the postganglionic sympathetic nerve ending that uses norepinephrine
and ATP as transmitters. Norepinephrine is known to increase cases
of chronic pain, and ATP is a stimulant of muscle nociceptors. If
BoNT inhibits the release of these transmitters, it could be analgesic
in cases of sympathetically maintained pain including the complex
regional pain syndrome.
PMID: 14991335
STUDIES N-Z
For a copy of this or any CRPS article,
visit McMaster Health Sciences Library. Search Pub Med using the
PMID number listed.
Pleger B, Tegenthoff M, Schwenkreis P, Janssen F, Ragert P, Dinse
HR, Volker B, Zenz M, Maier C.
Mean sustained pain levels are linked to hemispherical side-to-side
differences of primary somatosensory cortex in the complex regional
pain syndrome I.
Exp Brain Res. 2004 Mar;155(1):115-9. Epub 2004 Jan 27.
Department of Neurology, BG-Kliniken Bergmannsheil, Ruhr University
Bochum, Buerkle-de-la-Camp Platz 1, 44789, Bochum, Germany.
Chronic back pain as well as phantom-limb pain is characterized
by a close relationship between the amount of cortical reorganization
and the magnitude of pain. In patients with positively assessed
complex regional pain syndrome type I (CRPS I), we found a positive
correlation between representational changes of primary somatosensory
cortex (SI) and mean sustained pain levels. We investigated seven
right-handed patients with CRPS I of one upper limb by means of
somatosensory evoked potential (SSEP) mapping. Cortical representation
of the CRPS-affected hand was significantly smaller than that of
the contralateral healthy hand, giving rise to a substantial side
difference. Subjective pain levels experienced over the last 4 weeks
were estimated according to the visual analogue scale (VAS). Individual
expansion of hand representation contralateral to the CRPS-affected
limb was significantly correlated with mean pain intensity. Accordingly,
low pain levels were linked to small representational side-to-side
differences, while subjects with a distinctive hemispherical asymmetry
reported the highest pain levels. Follow-up studies using functional
imaging methods might be instrumental in providing a better understanding
of this issue.
PMID: 15064892
Pleger B, Janssen F, Schwenkreis P, Volker B, Maier C, Tegenthoff
M.
Repetitive transcranial magnetic stimulation of the motor
cortex attenuates pain perception in complex regional pain syndrome
type I.
Neurosci Lett. 2004 Feb 12;356(2):87-90.
Department of Neurology, Ruhr-University Bochum, BG-Kliniken Bergmannsheil,
Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany.
In complex regional pain syndrome (CRPS) many clinical symptoms
suggest involvement of the central nervous system. Neuropathic pain
as the leading symptom is often resistant to therapy. In the present
study we investigated the analgesic efficiency of repetitive transcranial
magnetic simulation (rTMS) applied to the motor cortex contralateral
to the CRPS-affected side. Seven out of ten patients reported decreased
pain intensities. Pain relief occurred 30 s after stimulation, whereas
the maximum effect was found 15 min later. Pain re-intensified increasingly
45 min after rTMS. In contrast, sham rTMS did not alter pain perception.
These findings provide evidence that in CRPS I pain perception can
be modulated by repetitive motor cortex stimulation.
Rizzo M, Balderson SS, Harpole DH, Levin LS.
Thoracoscopic sympathectomy in the management of vasomotor
disturbances and complex regional pain syndrome of the hand.
Orthopedics. 2004 Jan;27(1):49-52.
Division of Orthopedic, Duke University Medical Center, Box 3945,
Durham, NC 27710, USA.
Complex regional pain syndrome, vasospastic disorders, and hyperhidrosis
are chronic and debilitating upper extremity problems. Twenty-nine
consecutive patients treated with thoracoscopic sympathectomy are
presented. Diagnoses included complex regional pain syndrome, hyperhidrosis,
Buerger's disease, Raynaud's disease, and peripheral vascular disease.
All patients with hyperhidrosis had complete symptom resolution.
Patients with Buerger's and Raynaud's disease had excellent/good
results. Six patients with complex regional pain syndrome had excellent
or good relief; the remaining six patients had varying degrees of
recurrence. A statistically significant association was noted between
duration of complex regional pain syndrome prior to sympathectomy
and outcome. Thoracoscopic sympathectomy is an effective treatment
for hyperhidrosis and vasospastic disorders. Although the results
for complex regional pain syndrome are not uniformly excellent,
this technique offers promise in the treatment of this difficult
problem.
PMID: 14763530
CHARLES BERDE, MD PhD,
presenter at the Tampa conference, is a well known expert in
the treatment of CRPS in children and teens. The Pain Treatment
Service has treated over 600 children since 1986 and continues to
do so.There is also ongoing research at the Boston Hospital where
he works.
PHYSICAL THERAPY AND COGNITIVE BEHAVIOURAL
TREATMENT FOR CRPS
Berde CB,Lee BH, Scharff L, Sethna NF, McCarthy
CF, Scott-Sutherland J, Shea AM, Sullivan P, Meier P, Zurakowski
D,Masek BJ. 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 nonparametric 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 good.
PMID: 12091866
For a copy of this or any CRPS article,
visit McMaster Health Sciences Library. Search Pub Med using the
PMID number listed.
GENDER DIFFERENCES IN CRPS I/ RSD
IN CHILDREN AND ADOLESCENTS
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
sympathetic blocks.
RSDS IN CHILDREN AND ADOLESCENTS
(summary of Dr. Berde’s presentation at RSDSA's Tampa
conference)
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.
FURTHER READING
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:
IASP Press.
Sherry DD et al Short and long term outcomes of children with CRPS
1 treated with exercise therapy. Clinical Journal of Pain 1999;
15:218-33
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.
INTRODUCTION
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 studies.
KETAMINE-MIDAZOLAM ANAESTHESIA FOR INTRACTABLE
CRPS-1
INTRODUCTION
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.
METHODS
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.
OBSERVATIONS
INITIAL
All TEN responded by having no pain, no hyperalgesia, no allodynia
and an absence of CRPS-1 signs.
LONG TERM
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.
CONCLUSIONS
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
found.
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
REVIEW
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.
AIMS
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 ?
PATIENTS
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.
RESULTS
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.
CONCLUSIONS
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
time.
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.
STUDIES A-M
***Argoff CE. A focused review on the use of botulinum
toxins for neuropathic pain. Clin J Pain. 2002 Nov-Dec;18(6
Suppl):S177-81.
Cohn Pain Management Center, North Shore University Hospital, New
York University School of Medicine, Bethpage, New York 11714, USA.
pargoff@optonline.net
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.
PMID: 12569966
---------------
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
Wiley-Liss, Inc.
PMID: 12766967
-------------------
Bennett GJ. Are the complex regional pain syndromes due
to neurogenic inflammation?
Neurology. 2001 Dec 26;57(12):2161-2.
Comment on:
Neurology. 2001 Dec 26;57(12):2179-84.
Letter
PMID: 11756591
***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 (alees@ion.ucl.ac.uk)
* 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.
Abstract
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
April 2001
__________
***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
reactive hyperemia.
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
hypoxia.
[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.
PMID: 12562438
---------------------------------------------
STUDIES N-Z
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. candy.mccabe@rnhrd-tr.swest.nhs.uk
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.
PMID: 12509620
--------------------------------
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,
Australia.
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.
PMID: 12505953
------------------
***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.
Abstract
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
Netherlands. schasfoort@rev.fgg.eur.nl
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.
PMID: 12507702
-----------------------
Schouten AC, Van De Beek WJ, Van Hilten JJ, Van Der Helm FC.
Proprioceptive reflexes in patients with reflex sympathetic
dystrophy.
Delft University of Technology, Department of Mechanical Engineering,
Man Machine Systems and Control, Mekelweg 2, 2628 CD Delft, Leiden,
The Netherlands.
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.
PMID: 12743675
------------------------
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.
PMID: 12618683
-------------------------------------
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. sbc@cmc.cuk.ac.kr
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.
PMID: 12546368
---------------
van de Beek WJ, Schwartzman RJ, van Nes SI, Delhaas EM, van Hilten
JJ. Diagnostic criteria used in studies of reflex sympathetic
dystrophy.
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
define RSD.
PMID: 11865127
--------------
***van de Beek WJ, Vein A, Hilgevoord AA, van Dijk JG, van Hilten
BJ.
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.
PMID: 11896357
--------------
***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,
The Netherlands
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
DUTCH
RSD CONFERENCE
NOVEMBER 14-15 , 2003.
RSD AND THE SYMPATHETIC NERVOUS SYSTEM
R. Baron, Klink fur Neurologie, Christian-Alrechts-Universitat,
Kiel, Germany,
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
application of
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
syndromes.
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
changes.
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
Lancet 1993
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
1987
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
Med 2002
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”
inflammation.
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
disturbances.
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
limb trauma.
SPINAL CORD STIMULATION IN PATIENTS WITH CRPS TYPE 1:
LONG TERM RESULTS(translation)
M van Kleef, AZ Maastricht, Dept. of Anesthesiology and Pain Management,
Maastricht.
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
SCS.
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
EQ5D.
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
abnormal
posturing. These conditions constitute “faux CRPS” and
the patients are profoundly psychiatrically
impaired.
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
its symptoms.
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
approaches.
-----------------
Lecture notes:
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
CRPS?
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
enough.
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.
Introduction
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?
Hypothesis
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
reaction?
Lecture notes:
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:
| Type |
CRPS-1 patients |
Control Group |
| HLA-DR 6(cold RSD) |
50% |
31% |
| HLA-DQ 1(warmRSD) |
99% |
83% |
| TNF-a |
40% |
19% |
| Subgroup(more than one extremity) |
50% |
31% |
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.
File last updated April 2004.
|
