Robert J. Schwartzman

The movement disorder of reflex sympathetic dystrophy

We present 43 patients with reflex sympathetic dystrophy (RSD) who manifested abnormalities of movement. The patients have focal dystonia, weakness, spasms, tremor, difficulty initiating movement, and increased tone and reflexes. These motor signs and symptoms may precede other manifestations of the illness by weeks or months. They most frequently, but not invariably, occur concomitantly with sudomotor or vasomotor changes and pain. Lioresal is effective in reducing spasms. Early in the course of RSD, the motor manifestation may be alleviated by intense sympathetic blockade or sympathectomy. In many patients, the movement disorder becomes independent of sympathetic innervation.

Changes in cerebrospinal fluid levels of pro-inflammatory cytokines in CRPS

&NA; Complex Regional Pain Syndrome (CRPS) Types I and II are characterized by various combinations of sensory, autonomic and motor abnormalities. Pain disproportionate to the severity and duration of the inciting event is the most devastating symptom. In animal studies, conditions resulting in exaggerated pain states demonstrate elevated pro‐inflammatory cytokines. In addition, pro‐inflammatory cytokines have been shown to induce or increase neuropathic and inflammatory pain. Utilizing high sensitivity enzyme linked immunosorbent assay (ELISA), we compared the levels of the pro‐inflammatory cytokines interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and Tumor Necrosis Factor‐alpha (TNF‐α) in the cerebrospinal fluid (CSF) of patients afflicted with CRPS to CSF levels found in other patients with and without painful conditions. The results from this study demonstrated significant increases in IL‐1β and IL‐6, but not TNF‐α in the CSF of individuals afflicted with CRPS as compared to controls. CSF cytokine levels in controls with painful conditions did not differ from levels in controls without pain. These increases showed no correlation with the patients gender or weight. These results are consistent with studies that suggest that the pathogenesis of CRPS is due in part to central neuroimmune activation.

Patterns of spread in complex regional pain syndrome, type I (reflex sympathetic dystrophy)

&NA; There are reports that complex regional pain syndrome, type I (reflex sympathetic dystrophy; CRPS‐I/RSD) can spread from the initial site of presentation, but there are no detailed descriptions of the pattern(s) of such spread. We describe a retrospective analysis of 27 CRPS‐I/RSD patients who experienced a significant spread of pain. Three patterns of spread were identified. ‘Contiguous spread (CS)’ was noted in all 27 cases and was characterized by a gradual and significant enlargement of the area affected initially. ‘Independent spread (IS)’ was noted in 19 patients (70%) and was characterized by the appearance of CRPS‐I in a location that was distant and non‐contiguous with the initial site (e.g. CRPS‐I/RSD appearing first in a foot, then in a hand). ‘Mirror‐image spread (MS)’ was noted in four patients (15%) and was characterized by the appearance of symptoms on the opposite side in an area that closely matched in size and location the site of initial presentation. Only five patients (19%) suffered from CS alone; 70% also had IS, 11% also had MS, and one patient had all three kinds of spread. Our results suggest that CRPS‐I/RSD spread may not be a unitary phenomenon. In some it may be due to a local spread of pathology (CS); in others it may be a consequence of a generalized susceptibility (IS). In the MS case, spread may be due to abnormal neural functioning spreading via commissural pathways. Alternatively, we discuss the possibility that all three kinds of spread may be due to aberrant CNS regulation of neurogenic inflammation.

Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: A double-blind placebo controlled study

ABSTRACT Complex regional pain syndrome (CRPS) is a severe chronic pain condition that most often develops following trauma. The pathophysiology of CRPS is not known but both clinical and experimental evidence demonstrate the important of the NMDA receptor and glial activation in its induction and maintenance. Ketamine is the most potent clinically available safe NMDA antagonist that has a well established role in the treatment of acute and chronic pain. This randomized double‐blind placebo controlled trial was designed to evaluate the effectiveness of intravenous ketamine in the treatment of CRPS. Before treatment, after informed consent was obtained, each subject was randomized into a ketamine or a placebo infusion group. Study subjects were evaluated for at least 2 weeks prior to treatment and for 3 months following treatment. All subjects were infused intravenously with normal saline with or without ketamine for 4 h (25 ml/h) daily for 10 days. The maximum ketamine infusion rate was 0.35 mg/kg/h, not to exceed 25 mg/h over a 4 h period. Subjects in both the ketamine and placebo groups were administered clonidine and versed. This study showed that intravenous ketamine administered in an outpatient setting resulted in statistically significant (p < 0.05) reductions in many pain parameters. It also showed that subjects in our placebo group demonstrated no treatment effect in any parameter. The results of this study warrant a larger randomized placebo controlled trial using higher doses of ketamine and a longer follow‐up period.

The Natural History of Complex Regional Pain Syndrome

ObjectiveComplex regional pain syndrome (CRPS) is a severe chronic pain condition characterized by sensory, autonomic, motor, and dystrophic signs and symptoms. This study was undertaken to expand our current knowledge of the evolution of CRPS signs and symptoms with duration of disease. MethodThis was a retrospective, cross-sectional analysis using data extracted from a patient questionnaire to evaluate the clinical characteristics of CRPS at different time points of disease progression. Data from the questionnaire included pain characteristics and associated symptoms. It also included autonomic, motor, and dystrophic symptoms and also initiating events, ameliorating and aggravating factors, quality of life, work status, comorbid conditions, pattern of pain spread, family history, and demographics. Comparisons were made of different parameters as they varied with disease duration. ResultsA total of 656 patients with CRPS of at least 1-year duration were evaluated. The average age of all participants was 37.5 years, with disease duration varying from 1 to 46 years. The majority of participants were white (96%). A total of 80.3% were females. None of the patients in this study demonstrated spontaneous remission of their symptoms. The pain in these patients was refractory showing only modest improvement with most current therapies. DiscussionThis study shows that although CRPS is a progressive disease, after 1 year, the majority of the signs and symptoms were well developed and although many variables worsen over the course of the illness, the majority demonstrated only moderate increases with disease duration.

Efficacy of Ketamine in Anesthetic Dosage for the Treatment of Refractory Complex Regional Pain Syndrome: An Open‐Label Phase II Study

OBJECTIVE Advanced complex regional pain syndrome (CRPS) remains very difficult to treat. While subanesthetic low-dose ketamine has shown promise in early localized CRPS, its use in advanced CRPS has not been as effective. Since ketamines analgesic potency and duration of effect in neuropathic pain are directly dose-dependant, we investigated the efficacy of ketamine in anesthetic dosage in refractory CRPS patients that had failed available standard therapies. METHODS Twenty ASA I-III patients suffering from refractory CRPS received ketamine in anesthetic dosage over 5 days. Outcome criteria were pain relief, effect on the movement disorder, quality of life, and ability to work at baseline and up to 6 months following treatment. RESULTS Significant pain relief was observed at 1, 3, and 6 months following treatment (93.5 +/- 11.1%, 89.4 +/- 17.0%, 79.3 +/- 25.3%; P < 0.001). Complete remission from CRPS was observed at 1 month in all patients, at 3 months in 17, and at 6 months in 16 patients. If relapse occurred, significant pain relief was still attained at 3 and 6 months (59.0 +/- 14.7%, P < 0.004; 50.2 +/- 10.6%, P < 0.002). Quality of life, the associated movement disorder, and the ability to work significantly improved in the majority of patients at 3 and 6 months. CONCLUSIONS This open-label trial suggests benefit in pain reduction, associated CRPS symptoms, improved quality of life and ability to work following anesthetic ketamine in previously refractory CRPS patients. However, a randomized controlled trial will be necessary to prove its efficacy.

Epidural Spinal Cord Stimulation in the Management of Reflex Sympathetic Dystrophy

Eighteen subjects with intractable pain due to reflex sympathetic dystrophy (RSD) underwent treatment by epidural spinal cord Stimulation (SCS). All the patients had previously undergone multiple symp

Personality assessment of patients with complex regional pain syndrome type I.

OBJECTIVE There is controversy regarding the importance of psychological/psychiatric factors in the development of the Complex Regional Pain Syndrome (CRPS). Our objective was to determine whether CRPS type I patients were psychiatrically different from other chronic pain patients, with particular attention to personality pathology. DESIGN A standardized clinical assessment of all major psychiatric categories, including personality disorders, was performed on 25 CRPS type I patients and a control group of 25 patients with chronic low back pain from disc-related radiculopathy. MEASURES Both sections of the Structured Clinical Interview for the Diagnostic and Statistical Manual (3rd ed., rev.) and the visual analog scale. RESULTS Both groups were similar in terms of pain intensity and duration. Statistical analysis showed both groups to have a significant amount of major psychiatric comorbidity, in particular major depressive disorder, and a high incidence of personality disorders. Therefore, intense chronic pain was associated with significant psychiatric comorbidity in both groups and in similar proportions. CONCLUSION The high incidence of personality pathology in both groups may represent an exaggeration of maladaptive personality traits and coping styles as a result of a chronic, intense, state of pain.

Pathophysiology of complex regional pain syndrome

Complex regional pain syndrome (CRPS) most often follows injury to peripheral nerves or their endings in soft tissue. A combination of prostanoids, kinins and cytokines cause peripheral nociceptive sensitization. In time, the Mg2+ block of the N-methyl-D-aspartate receptor is removed, pain transmission neurons (PTN) are altered by an influx of Ca2+ that activates kinases for excitation and phosphatases for depression, activity-dependent plasticity that alters the firing of PTN. In time, these neurons undergo central sensitization that lead to a major physiological change of the autonomic, pain and motor systems. The role of the immune system and the sickness response is becoming clearer as microglia are activated following injury and can induce central sensitization while astrocytes may maintain the process.

High-dose cyclophosphamide without stem-cell rescue for refractory CIDP

Four patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who were refractory to conventional treatment were treated with high-dose cyclophosphamide (200 mg/kg over 4 days). All improved in functional status and muscle strength. Nerve conduction studies improved in three of four. Other immunomodulatory medications have been discontinued. High-dose cyclophosphamide can be given safely to patients with CIDP and patients with disease persistence after standard therapy may have a response that lasts for over 3 years and results in long-term disease remission.