Glomus tumor presenting as complex regional pain syndrome of the left upper limb: a case report.

BACKGROUND: Glomus tumors of the hand are rare, benign but debilitating neoplasms arising from the neuromyoarterial glomus body. They may present a diagnostic dilemma, and take years with multiple consultations and investigations before an appropriate diagnosis is made, but once a diagnosis is made, surgical excision is curative. CASE PRESENTATION: This is a case presentation of a 35-year-old African man who presented with complex regional pain syndrome of his left upper extremity, whose genesis was found to be a glomus tumor of the pulp of his left middle finger. Surgical excision resulted in resolution of the chronic regional pain syndrome and a return to a normal lifestyle. Chronic regional pain syndrome is a rare presentation of a glomus tumor, which has only been previously reported in patients with neurofibromatosis type 1, and one patient who did not have neurofibromatosis. CONCLUSIONS: Patients with glomus tumors may spend many years in pain and distress because of misdiagnosis. Sensitization and education of both the public and health care workers will help in early diagnosis and treatment of this otherwise potentially disabling pathology for which surgical excision is curative.

Effects of Targeted Proton Radiation on Spinal Cord in a Porcine Model: A Pilot Study.

AIM: To determine whether proton radiation can be used to treat chronic intractable pain. The focus of this study was on the biological effects of spinal cord irradiation. MATERIALS AND METHODS: Proton radiation (0-25 Gy, single fraction) was applied to the spinal cord within L3-L5 of Yucatan mini-pigs (n=20). Skin reaction, body mass and behavior were monitored. At euthanasia, blood and spinal cord were analyzed. RESULTS: Skin morbidity was mild and overall health for the 5-20 Gy-treated groups was good based on behavior and weight gain up to 8.5-9 months post-exposure. The 25 Gy-treated animals developed hind limb weakness at 2.5-3 months and were euthanized. Radiation had a significant effect on white blood cell count (p<0.05), with the 25 Gy-treated mini-pigs having the highest number of all three major leukocyte populations. A few differences were also noted for erythrocyte parameters, but the blood chemistry panel was normal. Apoptosis in the targeted portion of the spinal cord was elevated in the 20- and 25 Gy-treated groups versus 0 Gy (p<0.05) based on the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. There was a trend (p<0.1) for a radiation effect on glial fibrillary acidic protein expression, with the highest value being found after 25 Gy. Histology showed no difference between 0 versus 25 Gy. CONCLUSION: The data demonstrated that a small segment of the spinal cord can be readily targeted using proton radiation; doses ranging from 5-20 Gy were well-tolerated in an animal model with radiosensitivity similar to humans. Future studies with a pain model should use ≤15 Gy.

Spinal stimulator peri-electrode masses: case report.

The authors describe a case of delayed spastic quadriparesis caused by a peri-electrode mass following the implantation of a minimally invasive percutaneous spinal cord stimulator (SCS). Prior reports with paddle-type electrodes are reviewed, and a detailed histological and pathophysiological comparison with the present case is made. The patient developed tolerance to a cervical percutaneous SCS 4 months after implantation, followed by the onset of spastic quadriparesis 9 months after implantation. The stimulator was removed, and contrast-enhanced MRI revealed an enhancing epidural mass where the system had been placed, with severe spinal cord compression. Decompression was carried out, and the patient experienced neurological improvement. Pathological examination revealed fibrotic tissue with granulomatous and multinucleated giant cell reactions. No evidence of infection or hemorrhage was found. Professionals treating patients with SCSs or contemplating their insertion should be aware of this delayed complication and associated risk factors.

Management of advanced plexiform neurofibromatosis of the foot presenting with skeletal deformation and intractable pain: an indication for proximal amputation.

Plexiform neurofibromas of the foot are rare and often present with significant pain, deformity, and functional impairment secondary to their locally invasive behavior. While treatment has traditionally focused on attempts at radical resection, a lack of consensus among surgeons has hindered the establishment of a well-defined algorithm to guide the management of these highly co-morbid peripheral nerve sheath tumors. We present the case of an advanced plexiform neurofibroma of the right foot in a 24-year-old male with neurofibromatosis type 1. The patient presented following accelerated tumor growth with extensive osseous erosion, intractable pain, and progressive ankle instability that limited his capacity to ambulate and wear shoes. A modified transtibial amputation with a vascularized fibular bone graft (Ertl procedure) was performed without complication. Following graduated rehabilitation, postoperatively, the patient regained functional independence and was able to ambulate without pain in a customized prosthesis after 3 months. Plexiform neurofibromas of the foot present a complex challenge for foot and ankle surgeons. On the basis of our experience and previously reported cases, we advocate for amputation over aggressive attempts at advanced limb salvage for patients with extensive skeletal destruction, joint instability, and/or intractable pain caused by tumor mass effect.

Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis.

Abstract Doxycycline inhibits amyloid formation in vitro and its therapeutic efficacy is under evaluation in clinical trials for different protein conformational diseases, including prion diseases, Alzheimer's disease and transthyretin amyloidosis. In patients on chronic hemodialysis, a persistently high concentration of ß2-microglobulin causes a form of amyloidosis (dialysis-related amyloidosis, DRA) localized in bones and ligaments. Since doxycycline inhibits ß2-microglobulin fibrillogenesis in vitro and accumulates in bones, DRA represents an ideal form of amyloidosis where doxycycline may reach a therapeutic concentration at the site of amyloid deposition. Three patients on long-term dialysis with severe articular impairment and uncontrollable pain due to DRA were treated with 100 mg of doxycycline daily. Pharmacokinetics and safety of treatment were conducted. Plasmatic levels of the drug reached a plateau after one week (1.1-2.3 µg/ml). Treatment was well tolerated in two patients for a year, while one was suspended after 5 months due to mild esophagitis. Treatment was associated with a significant reduction in articular pain and with a significant and measurable improvement in passive and active movements in all cases, despite the persistence of unchanged amyloid deposits measured by magnetic resonance imaging.

Microglia and intractable chronic pain.

Many pathological processes within the central nervous system are mediated by complex interactions between neurons and resident glial cells. In the case of painful peripheral neuropathy, spinal microglia react and undergo a series of changes that directly influence the establishment of neuropathic pain states. Purinergic signaling has been shown to be at the center of this reactivity, and here we review recent mechanistic advances describing the importance of microglial P2 receptors and their interactions with neuronal populations in the development of neuropathic pain.

Psoas syndrome: a frequently missed diagnosis.

Psoas syndrome is an easily missed diagnosis. However, it is important to consider this condition as part of the differential diagnosis for patients presenting with low back pain--particularly for osteopathic physicians, because patients may view these practitioners as experts in musculoskeletal conditions. The authors describe the case of a 48-year-old man with a 6-month history of low back pain that had been attributed to "weak core muscles." The diagnosis of psoas syndrome was initially overlooked in this patient. After the correct diagnosis was made, he was treated by an osteopathic physician using osteopathic manipulative treatment, in conjunction with at-home stretches between office treatments. At his 1-month follow-up appointment, he demonstrated continued improvement of symptoms and a desire for further osteopathic manipulative treatment.

Anatomical variations of the lateral nasal wall: The secondary and accessory middle turbinates.

The aim of the current anatomical and clinical study was to audit our cases of patients who presented with secondary and/or accessory middle turbinates during a two-year period. We investigated the incidence and the clinical impact of these variations. Twenty-eight patients, 19 males and 9 females with a mean age of 41.5 years, representing different ethnic origins, were diagnosed with double middle turbinates based on endoscopic examination. Of those, 92.8% had a main symptom of refractory frontal headache. A secondary nasal symptom was sensation of blocked nose. Patients who underwent endoscopic surgery (n = 13) for reduction of the extra turbinate, reported significant symptom scores improvement (P < 0.0001) of frontal headache and blocked nose, from means of 9.07 ± 0.26 and 8.57 ± 1.39 to 1 ± 0.31, and 1.42 ± 0.35, respectively. Our results indicate that double middle turbinates may be encountered in rhinology practice (2%). Clinically they may present with refractory headache and blocked nose. Endoscopic surgical approach seems to be an effective way of improving the symptoms.

Deep brain stimulation for Dejerine-Roussy syndrome: case report.

BACKGROUND: The term "central post-stroke pain" is more appropriate to describe neuropathic pain following a cerebrovascular accident. Most patients complain of burning and other symptoms like lacerating and shooting pain. Treatment options for central pain are limited in number and efficacy. CASE REPORT: This paper reports on a 47-year-old man with central post-stroke pain refractory to treatment. The patient underwent insertion of a deep brain stimulator utilizing the Leksell frame. The target was the left centromedian thalamic nuclei. He had a qualitative symptomatic improvement. CONCLUSION: Deep brain stimulation can be a useful tool when all other modalities have failed. It is a minimally invasive neurosurgical procedure that may improve the quality of life in carefully selected (often desperate) patients with central post-stroke pain.

Cancer pain and its relationship to systemic inflammation: an exploratory study.

Pain is the commonest symptom in cancer patients, whereas inflammation is implicated in cancer development and progression. The relationship between pain and inflammation in cancer is therefore of interest; however, it is challenging to examine because multiple factors may affect these variables. This study assessed the relationship between cancer pain and systemic inflammation using a retrospective analysis of 2 clinical trial datasets of patients with cancer cachexia. Included patients had gastrointestinal, lung, or pancreatic cancer. Pain was assessed using the pain subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-30. Inflammation was assessed using C-reactive protein (CRP). A regression analysis between pain and logarithmically transformed CRP was run, and Pearson correlation coefficients were calculated. A total of 718 patients entered the trials, of whom 449 had CRP measured. Both trial populations were well matched. Pain positively correlated with CRP. The Pearson correlation coefficients were 0.126 and 0.163 for trials 1 and 2, respectively. This correlation was statistically significant at the P<.05 level. These findings support that pain is related to systemic inflammation in a cohort of cancer patients. Many factors can affect pain and inflammation in cancer, demonstrating that any relationship that exists between pain and inflammation is of interest. This is in keeping with work showing this relationship in nonmalignant pain. Studies targeting inflammation and assessing its effect on pain in cancer would be an important step in the research agenda.

Peripheral formalin injury induces 2 stages of microglial activation in the spinal cord.

UNLABELLED: The formalin test produces 2 well-known acute phases of nociceptive behavior. Recently, we have shown that this same formalin test produces a third phase of nociceptive behavior consisting of prolonged thermal and mechanical hyperalgesia beginning days after formalin injection and lasting for at least 3 weeks. Here we investigated the activity of 3 MAPKs (p38, ERK and JNK) in the spinal dorsal horn following 5% formalin injection into rat hind paw. The p38 MAPK was rapidly activated in the spinal microglia minutes after injection and the activation persisted for 1 hour. In addition, this same injury induced a secondary increase of phospho-p38 expression in spinal microglia that was maximal 3 to 7 days postinjection. Intrathecal administration of p38 inhibitor SB203580 not only inhibited the early acute spontaneous nociceptive behaviors, but also inhibited the long-term formalin injury-induced mechanical hyperalgesia. Our results suggest that peripheral formalin injection induces 2 stages of microglial activation, and p38 activation in spinal microglia plays key roles in central pain modulation in formalin test respectively for the early acute phases and the late secondary long-term pain state as well. PERSPECTIVE: This article presents unique properties of spinal microglial activation in a pain animal model. This finding could potentially help clinicians to further understand the contributions of spinal microglia to acute and chronic pain state.

Minocycline attenuates mechanical allodynia and central sensitization following peripheral second-degree burn injury.

UNLABELLED: Burn injury induces severe pain that can be refractory to existing pharmacotherapies. The underlying mechanism of burn pain remains unclear. We previously established an animal model and reported that unilateral burn injury induces chronic and bilateral mechanical allodynia, which is associated with central sensitization and microglial activation in the spinal cord dorsal horn. Modulation of the activity of microglia and p38 mitogen-activated protein kinase (MAPK) has been shown to ameliorate neuropathic pain in several nerve-injury pain models. In the present study, we show in this rat model that daily treatment with the microglial inhibitor minocycline (10 mg/kg), administered at the time of burn injury and for 7 days thereafter, significantly attenuates ipsilateral and contralateral allodynia as assessed up to 1 month following burn injury. These sensory changes are paralleled by significant suppression of evoked hyperexcitability of dorsal-horn neurons and of the expression of phosphorylated p38 (phospho-p38) in OX42+ microglial cells within the dorsal horn. Our results suggest that modulation of inflammation at early times after burn injury may have long-lasting effects, attenuating central neuropathic mechanisms which contribute to pain after burn injury. PERSPECTIVE: We demonstrate, in a rodent model of burn-associated pain, that the microglial inhibitor minocycline, delivered at the time of burn injury and for 1 week thereafter, has long-lasting effects, attenuating microglial activation and neuronal hyperresponsiveness in the dorsal horns, and ameliorating allodynia for at least 1 month.

Clinical presentation of asbestosis with intractable pleural pain in the adult child of a taconite miner and radiographic demonstration of the probable pathology causing the pain.

Taconite, although not classified by the United States Government as asbestos or asbestiform material, has been associated with asbestos-related diseases. The mineral is used in the production of steel and as a road-patch material and is mined in Michigan and Minnesota. This report describes the case of a middle-aged Caucasian woman with exposure to taconite mining dust from her miner father's clothing in childhood with a resultant presentation consistent with asbestosis and intractable pleural pain. Intractable pleural pain has been described in asbestos-exposed patients with theorized etiologies. However, no in vivo reported mechanism has demonstrated a plausible, anatomically apparent mechanism for the pain. We utilize an application of the Vitrea software for enhancement of high-resolution computerized tomography which demonstrates at least one likely mechanism for intractable pleural pain.

Historic evolution of open cingulectomy and stereotactic cingulotomy in the management of medically intractable psychiatric disorders, pain and drug addiction.

Stereotactic cingulotomy constitutes a psychosurgical procedure nowadays advocated in the treatment of medically intractable obsessive-compulsive disorder, chronic pain and drug addiction. From its theoretical conception to the first cingulectomies performed and modern stereotactic-guided cingulotomies, various target localization methods, different surgical techniques, and numerous lesioning devices have been utilized. In the current article, the authors performed a literature review related to cingular lesion placement in an effort to identify misconceptions of the past, recapitulate existing knowledge and recognize targets for further research. The initial animal and human electrophysiologic experimental data regarding the role of the cingulate cortex in various behavioral and cognitive functions were meticulously reviewed. The clinical indications, surgical technique and the clinical results and complications of open cingulectomies were examined. The anatomic target localization methodologies, surgical technique, and the outcome of the initial stereotactic cingulotomy procedures were reviewed, and the evolution of the imaging techniques, stereotactic devices, and lesioning strategies were followed. The modern advanced surgical techniques, clinical outcome and the procedure-associated complications were analyzed with particular emphasis on the emotional, behavioral, and cognitive procedure-induced changes. Large-scale prospective studies with strict inclusion and well-defined, objective outcome criteria are necessary for defining the role of stereotactic cingulotomy in the current psychosurgical armamentarium.

Dorsal root entry zone lesions for phantom limb pain with brachial plexus avulsion: a study of pain and phantom limb sensation.

BACKGROUND: Lesions in the dorsal root entry zone (DREZ) have been shown to be significantly effective in relieving the pain of brachial plexus avulsion (BPA), but they have a limited effect on phantom limb pain (PLP). There is still the question remaining of whether DREZ lesions are effective in treating PLP in cases of BPA. METHODS: Our study includes 14 post-traumatic patients with BPA and upper limb amputation. All developed PLP and underwent DREZ lesions. After the surgery, patients were asked to estimate the global percent of pain relief (0-100%). The phantom limb sensation (PLS) was also inquired after. RESULTS: Overall, 9 (64.3%) of 14 patients had satisfactory pain relief; the mean follow-up was 15.2 +/- 6.6 months. Among the 9 patients with satisfactory pain relief, PLS had altered in 6 (66.7%), while, in the other 5 patients with poor pain relief, none had experienced alterations in PLS. CONCLUSION: DREZ lesions are effective in the treatment of PLP with BPA. Alteration in PLS after the surgery may be a predictive factor for good pain relief. The good response of PLP patients with BPA to DREZ lesions suggests that an evaluation of the cervical dorsal roots should be conducted in patients with post-traumatic PLP.

Inverse relation between intensity of GFAP expression in the substantia gelatinosa and degree of chronic mechanical allodynia.

Glial cells are known to have a large impact on neuropathic pain conditions. Within the spinal cord, microglia rapidly respond to peripheral nerve injury, resulting in central sensitization and ultimately in the onset of enhanced pain behaviour. Astroglia respond with a short delay and are thought to contribute to the early maintenance of neuropathic pain. Nevertheless, it is unknown whether the roles of these glial cell types can be influenced by the chronicity of the neuropathology. Here, the persistent responses of astroglia and microglia to peripheral nerve injury within central pain networks in the upper dorsal horn laminae were studied. At 12 weeks after complete sciatic nerve injury, upregulation of glial fibrillary acidic protein (GFAP), but not complement receptor-3, could be detected in laminae II and III. Moreover, it was found that neuropathic animals with a higher degree of mechanical allodynia had a lower intensity of GFAP expression in lamina II (substantia gelatinosa). From these data we conclude that the role of astroglial responses in mechanical allodynia after peripheral nerve injury may be less straightforward as previously thought. Although astroglia are known to play a pro-nociceptive role in early neuropathic pain states, this role may shift to anti-nociception in more chronic pain states.

Impact of bilateral anterior cingulotomy on neurocognitive function in patients with intractable pain.

Although the cingulate cortices are important with regard to neurocognitive functions, outcome studies usually fail to identify evident cognitive dysfunction following anterior cingulotomy. The aim of this study was to document any impairment of neurocognitive functions following anterior cingulotomy. Between September 2002 and April 2004, 10 patients underwent stereotactic bilateral anterior cingulotomy for intractable cancer pain. A neuropsychological assessment of each patient was performed 1 day prior to surgery and 1 week and 1 month post-operatively. Assessment of pain relief was evaluated with a short form of the McGill pain questionnaire. Six of the 10 patients achieved fair to good pain relief following the cingulotomy procedure. Most neurocognitive functions, including language, memory, motor, visual-constructional, and intellectual functions, remained unaffected. A decline in focused attention performance was identified at the early post-operative assessment. The results of this longitudinal evaluation will help to better define the risk-to-benefit profile of cingulotomy for intractable pain.