Spinal Cord Stimulation for Visceral Pain: Present Approaches and Future Strategies.

INTRODUCTION: The introduction of successful neuromodulation strategies for managing chronic visceral pain lag behind what is now treatment of choice in refractory chronic back and extremity pain for many providers in the United States and Europe. Changes in public policy and monetary support to identify nonopioid treatments for chronic pain have sparked interest in alternative options. In this review, we discuss the scope of spinal cord stimulation (SCS) for visceral pain, its limitations, and the potential role for new intradural devices of the type that we are developing in our laboratories, which may be able to overcome existing challenges. METHODS: A review of the available literature relevant to this topic was performed, with particular focus on the pertinent neuroanatomy and uses of spinal cord stimulation systems in the treatment of malignant and nonmalignant gastrointestinal, genitourinary, and chronic pelvic pain. RESULTS: To date, there have been multiple off-label reports testing SCS for refractory gastrointestinal and genitourinary conditions. Though some findings have been favorable for these organs and systems, there is insufficient evidence to make this practice routine. The unique configuration and layout of the pelvic pain pathways may not be ideally treated using traditional SCS implantation techniques, and intradural stimulation may be a viable alternative. CONCLUSIONS: Despite the prevalence of visceral pain, the application of neuromodulation therapies, a standard approach for other painful conditions, has received far too little attention, despite promising outcomes from uncontrolled trials. Detailed descriptions of visceral pain pathways may offer several clues that could be used to implement devices tailored to this unique anatomy.

Pseudoanginal chest pain associated with vagal nerve stimulation: a case report.

BACKGROUND: Vagal nerve stimulation (VNS) can be an effective therapy for patients with epilepsy refractory to anti-epileptic drugs or intracranial surgery. While generally well tolerated, it has been associated with laryngospasm, hoarseness, coughing, dyspnea, throat and atypical chest pain, cardiac symptoms such as bradycardia and occasionally asystole. We report on a patient receiving vagal nerve stimulation who experienced severe typical anginal chest pain during VNS firing without any evidence of cardiac ischemia or dysfunction. Thus, the pain appeared to be neuropathic from the stimulation itself rather than nociceptive secondary to an effect on heart function. CASE PRESENTATION: A 29-year-old man, with a history of intractable frontal lobe epilepsy refractory to seven anti-epileptic medications and subsequent intracranial surgery, underwent VNS implantation without complications. On beginning stimulation, he began to have intermittent chest pain that corresponded temporally to his intermittent VNS firing. The description of his pain was pathognomonic of ischemic cardiac chest pain. On initial evaluation, he displayed Levine's sign and reported crushing substernal chest pain radiating to the left arm, as well as shortness of breath walking upstairs that improved with rest. He underwent an extensive cardiac workup, including 12-lead ECG, cardiac stress test, echocardiogram, 12-day ambulatory cardiac monitoring, and continuous ECG monitoring each with and without stimulation of his device. The workup was consistently negative. Inability to resolve the pain necessitated the disabling and eventual removal of the device. CONCLUSION: To our knowledge, this is the first report of pseudoanginal chest pain associated with VNS. This occurrence prompted our review of the mechanisms of cardiac chest pain and suggests that vagal afferents may convey anginal pain separately or in parallel with known spinal cord pain mechanisms. These insights into the physiology of chest pain may be of general interest and important to surgeons implanting VNS devices who may potentially encounter such symptoms.

Coexistent intraventricular abnormalities in periventricular giant arachnoid cysts.

OBJECT: Arachnoid cysts are congenital lesions that arise during development by splitting of the arachnoid membrane. Large cysts can be adjacent to CSF pathways causing a marked midline shift and hydrocephalus. The association between a large arachnoid cyst and hydrocephalus has been commonly described as being due to a mass effect, but these previous reports have not focused closely on any associated intraventricular abnormalities. METHODS: Seven patients who were previously treated with a cystoperitoneal shunt presented with shunt failure, hydrocephalus, and/or cyst expansion. All of these patients had giant arachnoid cysts extending to the periventricular region from the original site, which was the sylvian fissure in 4 patients, and the suprasellar cistern, quadrigeminal cistern, and interhemispheric fissure in 1 patient each. Endoscopic exploration of the ventricular system and cyst fenestration was then performed in all patients. RESULTS: The endoscopic findings were obstruction of the cerebral aqueduct by a membrane not related to the cyst in 5 patients, occlusion of the foramen of Monro in 6, septum pellucidum hypoplasia in 2, and occlusion of the cerebral aqueduct by a quadrigeminal arachnoid cyst in 1. Endoscopic procedures performed were septum pellucidum fenestration and/or foraminoplasty in 5 patients, aqueductoplasty in 2, endoscopic third ventriculostomy in 5, fenestration of the lamina terminalis in 1, and direct cystocisternostomy in 1. After the endoscopic procedure, signs and symptoms of increased intracranial pressure and hydrocephalus improved in all patients, with a reduction in size of the cyst and the ventricle. CONCLUSIONS: Ventricular abnormalities contributing to hydrocephalus may be associated with arachnoid cysts. These abnormalities may more likely reflect a common origin than a casual relation. Foramen of Monro stenosis and cerebral aqueduct occlusion associated with an arachnoid cyst can be more frequent than has been previously believed. In cases of periventricular giant arachnoid cysts, endoscopic exploration is a good alternative for examining the ventricular system and identifying and treating CSF obstructions caused by and/or related to arachnoid cysts.

Apnea and macrocephaly-cutis marmorata telangiectatica congenita.

The authors report a case of an infant girl with macrocephaly-cutis marmorata telangiectatica congenita (Macrocephaly-CMTC). This patient presented with developmental delay, mild subcostal retractions, and occasional apneic spells. An MRI demonstrated mild to moderate lateral ventricle hydrocephalus, left hemi-megalencephaly, and left cerebellar tonsillar herniation with full occlusion of the cisterna magna. Her foramen magnum was narrowed, measuring 17.5mm in transverse diameter. This value was significantly below the 50th percentile for age, which is 23.5mm. Together, these findings were suggestive of cervicomedullary cord compression, concerning for sudden death. The patient underwent posterior fossa decompression by suboccipital craniectomy and cervical laminectomy. Initially due to hypertrophy and paralysis of the left true and false vocal cords, endotracheal intubation was not achieved, requiring tracheostomy tube placement. To our knowledge this is the first report of apnea in a patient diagnosed with M-CMTC, likely due to cervicomedullary cord compression and perhaps exacerbated by unilateral laryngeal hypertrophy. M-CMTC is a newly-described hemi-hypertrophy syndrome affecting the neurodevelopment of affected children. The authors emphasize airway obstruction secondary to unilateral hypertrophy of the vocal cords in addition to brainstem compromise as a consideration for the etiology of apnea in M-CMTC patients presenting with signs and symptoms of cervicomedullary cord compression.

A new technique allowing prolonged temporary cerebral artery occlusion.

OBJECT: Clipping of complex cerebral aneurysms often requires temporary vessel occlusion. The risk of stroke, however, increases exponentially with occlusion time. The authors hypothesized that prolonged temporary occlusion might be tolerated if the occluded vessels were perfused with cold physiological saline solution (CPSS). A low-flow perfusion rate would permit surgical manipulation of an aneurysm distal to the occlusion. METHODS: To test this hypothesis, the authors temporarily occluded the middle cerebral artery (MCA) with an endovascular catheter in 6 rats. Three animals, the treatment group, were perfused with 5-ml CPSS/hour through the occluding endovascular catheter into the MCA, and the other 3 served as an ischemic control group. In both groups, the catheter was removed after 90 minutes of occlusion. The brain temperature was monitored with a stereotactically placed probe in the caudate-putamen in 2 separate experimental groups (11 animals). RESULTS: Magnetic resonance imaging perfusion scanning during vessel occlusion confirmed similar reduction of cerebral blood flow during MCA occlusion in both the simple-occlusion and perfusion-occlusion groups. Magnetic resonance imaging diffusion scans performed 24 hours after temporary occlusion revealed infarcts in the ischemic control group of 138.3 +/- 28.0 mm(3) versus 9.9 +/- 9.9 mm(3) in the cold saline group (p < 0.005). A focal cooling effect during perfusion with CPSS was demonstrated (p < 0.05). CONCLUSIONS: Prolonged temporary cerebral vessel occlusion can be tolerated using superselective CPSS perfusion through an occluding endovascular catheter into the ischemic territory. This technique could possibly be applied in neurosurgery practice to the management of complex intracranial aneurysms.

Cerebral pressure autoregulation in traumatic brain injury.

An understanding of normal cerebral autoregulation and its response to pathological derangements is helpful in the diagnosis, monitoring, management, and prognosis of severe traumatic brain injury (TBI). Pressure autoregulation is the most common approach in testing the effects of mean arterial blood pressure on cerebral blood flow. A gold standard for measuring cerebral pressure autoregulation is not available, and the literature shows considerable disparity in methods. This fact is not surprising given that cerebral autoregulation is more a concept than a physically measurable entity. Alterations in cerebral autoregulation can vary from patient to patient and over time and are critical during the first 4-5 days after injury. An assessment of cerebral autoregulation as part of bedside neuromonitoring in the neurointensive care unit can allow the individualized treatment of secondary injury in a patient with severe TBI. The assessment of cerebral autoregulation is best achieved with dynamic autoregulation methods. Hyperventilation, hyperoxia, nitric oxide and its derivates, and erythropoietin are some of the therapies that can be helpful in managing cerebral autoregulation. In this review the authors summarize the most important points related to cerebral pressure autoregulation in TBI as applied in clinical practice, based on the literature as well as their own experience.

The role of c-AMP-dependent protein kinase in spinal cord and post synaptic dorsal column neurons in a rat model of visceral pain.

Visceral noxious stimulation induces central neuronal plasticity changes and suggests that the c-AMP-dependent protein kinase (PKA) signal transduction cascade contributes to long-term changes in nociceptive processing at the spinal cord level. Our previous studies reported the clinical neurosurgical interruption of post synaptic dorsal column neuron (PSDC) pathway by performing midline myelotomy effectively alleviating the intractable visceral pain in patients with severe pain. However, the intracellular cascade in PSDC neurons mediated by PKA nociceptive neurotransmission was not known. In this study, by using multiple experimental approaches, we investigated the role of PKA in nociceptive signaling in the spinal cord and PSDC neurons in a visceral pain model in rats with the intracolonic injection of mustard oil. We found that mustard oil injection elicited visceral pain that significantly changed exploratory behavior activity in rats in terms of decreased numbers of entries, traveled distance, active and rearing time, rearing activity and increased resting time when compared to that of rats receiving mineral oil injection. However, the intrathecal infusion of PKA inhibitor, H89 partially reversed the visceral pain-induced effects. Results from Western blot studies showed that mustard oil injection significantly induced the expression of PKA protein in the lumbosacral spinal cord. Immunofluorescent staining in pre-labeled PSDC neurons showed that mustard oil injection greatly induces the neuronal profile numbers. We also found that the intrathecal infusion of a PKA inhibitor, H89 significantly blocked the visceral pain-induced phosphorylation of c-AMP-responsive element binding (CREB) protein in spinal cord in rats. The results of our study suggest that the PKA signal transduction cascade may contribute to visceral nociceptive changes in spinal PSDC pathways.

Spontaneous spinal epidural arteriovenous fistulae in neurofibromatosis type-1.

BACKGROUND: NF-1 is one of the most common autosomal-dominantly inherited genetic disorders with an incidence of approximately 1:3500. We report a case and review the literature to characterize spontaneous spinal AVF that occur in neurofibromatosis (NF-1). CASE REPORT: A 51-year-old woman presented with NF-1 and progressive radiculomyelopathy. Angiography revealed an AVF terminating in a giant intraspinal epidural varix extending paraspinally through the C3/4 neural foramen. Trapping of the AVF attempted 18 years earlier prevented endovascular access for embolization, and vigorous bleeding made direct surgical resection impossible. Therefore, as palliation, arterial feeding collaterals were occluded, and surgically exposed tortuous veins were packed with coils. Laminectomies and partial resection of the epidural varix resulted in subtotal occlusion with clinical improvement. CONCLUSION: The spinal AVF associated with NF-1 appears to show dominant venous drainage to the intraspinal extradural and paraspinal venous plexus without evidence of intradural drainage. The vertebral artery is typically the origin of the fistula. A giant venous varix and numerous collateral feeders to the vertebral artery may give an AVM-like appearance. Clinically, the fistulae produce a syndromic triad including symptoms of NF-1, progressive radiculomyelopathy, and a bruit. Treatment is direct attack on the fistula by either surgery or embolization. If, however, a direct approach cannot be chosen, occlusion of feeding vessels combined with laminectomies can result in long-term symptomatic improvement.

Development and implementation of a problem-focused neurological assessment system.

A menu-driven, problem-focused neurological assessment system was constructed and implemented after concerns at a six-hospital teaching center about the quality of nursing assessments for patients with neurological diagnoses were validated. This system enables the physician to guide the nurse's assessment by ordering specific neurological tests for each patient. Extensive staff training took place to develop competence with this system. This new system has resulted in positive changes for this facility. Nurses acknowledge greater comfort with performing neurological assessment; documentation of assessment has improved; and the assessments are becoming more individualized for each patient. This system resulted in a higher quality of neurological care for patients.

Preoperative embolization and intraoperative cryocoagulation as adjuncts in resection of hypervascular lesions of the thoracolumbar spine.

OBJECT: The purpose of this study was twofold. First the authors evaluated preoperative embolization alone to reduce estimated blood loss (EBL) when resecting hypervascular lesions of the thoracolumbar spine. Second, they compared this experience with intraoperative cryotherapy alone or in conjunction with embolization to minimize further EBL. METHODS: Twelve patients underwent 13 surgeries for hypervascular spinal tumors. In 10 cases the surgeries were augmented by preoperative embolization alone. In one patient, two different surgeries involved intraoperative cryocoagulation, and in one patient surgery involved a combination of preoperative embolization and intraoperative cryocoagulation for tumor resection. When cryocoagulation was used, its extent was controlled using intraoperative ultrasonography or by establishing physical separation of the spinal cord from the tumor. In the 10 cases in which embolization alone was conducted, intraoperative EBL in excess of 3 L occurred in five. Mean EBL was of 2.8 L per patient. In one patient, who underwent only embolization, excessive bleeding (> 8 L) required that the surgery be terminated and resulted in suboptimum tumor resection. In another three cases, intraoperative cryocoagulation was used alone (in two patients) or in combination with preoperative embolization (in one patient). In all procedures involving cryocoagulation of the lesion, adequate hemostasis was achieved with a mean EBL of only 500 ml per patient. No new neurological deficits were attributable to the use of cryocoagulation. CONCLUSIONS: Preoperative embolization alone may not always be satisfactory in reducing EBL in resection of hypervascular tumors of the thoracolumbar spine. Although experience with cryocoagulation is limited, its use, in conjunction with embolization or alone, suggests it may be helpful in limiting EBL beyond what can be achieved with embolization alone. Cryocoagulation may also assist resection by preventing spillage of tumor contents, facilitating more radical excision, and enabling spinal reconstruction. The extent of cryocoagulation could be adequately controlled using ultrasonography or by establishing physical separation between the tumor and spinal cord. Additionally, somatosensory evoked potential monitoring may provide early warning of spinal cord cooling.

Chemical shift imaging of mannitol in acute cerebral ischemia. Case report.

The effectiveness of mannitol for the treatment of cerebral edema after stroke has long been debated, and the diffusion of mannitol through a disrupted blood-brain barrier has been the focus of many contradictory studies. The authors present a unique case in which chemical shift imaging was used to demonstrate the accumulation of mannitol in an area of stroke underlying a subdural hematoma in a patient with end-stage renal disease being treated with hemodialysis. A metabolite map for the xenobiotic mannitol was created from the data and demonstrated the accumulation of mannitol when hemodialysis was interrupted prematurely. Metabolite maps were also used to show removal of the mannitol with the reestablishment of hemodialysis. It is concluded that mannitol can accumulate in an area of infarction, and that chemical shift imaging can be used to illustrate this process.