Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuromyelitis optica (NMO) or Devic's disease is an inflammatory neurologic disease characterized by severe optic neuritis and transverse myelitis. Other features of NMO include female preponderance, higher onset age, severe functional disability, longitudinally extensive spinal cord lesions (longer than 3 vertebral segments), and oligoclonal IgG bands negativity. Brain lesions are not uncommon in NMO. The relation between NMO and multiple sclerosis (MS) has long been a matter of controversy, but since the discovery of anti-aquaporin 4 (AQP4) antibody (NMO-IgG), an NMO-specific autoantibody, the clinical, MRI, and laboratory features that distinguish NMO from MS have been clarified. Anti-AQP4 antibody binds to the extracellular domain of AQP4, which is highly expressed in endfeet of astrocytes. Recent neuropathological studies, analysis of CSF-GFAP levels during relapse and experimental studies strongly suggest that NMO is an anti-AQP4 antibody-mediated astrocytopathic disease and that T cell-mediated CNS inflammation is necessary to develop NMO. Also, IL-6 is remarkably elevated in the CSF and appears to regulate plasmablasts to produce anti-AQP4 antibody. Therefore, from the therapeutic point of view, depletion of anti-AQP4 antibody, suppression of T cell response to trigger relapse and anti-IL-6 therapy seem to be pivotal. High-dose intravenous methylprednisolone is the first-line therapy for acute exacerbations of NMO. But plasma exchange should be started soon if corticosteroid is not efficacious. If untreated, AQP4 antibody-positive patients are highly likely to experience relapses within a year. Thus, immunosuppressive therapy (corticosteroids, immunosuppressants, rituximab) should be initiated without delay. Preliminary results suggest that eculizumab, an anti-C5 monoclonal antibody, can also prevent relapse in NMO, Meanwhile, interferon-beta, a first-line disease modifying drug of MS, is not effective in NMO. Symptomatic therapy for pain, paresthesia, spasticity, dysuria and constipation which commonly occur in the chronic stage of NMO is also important to improve patients' quality of life.
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PMID:[Treatment of neuromyelitis optica]. 2257 70

Thecaloscopy is less invasive exploration of spinal subarachnoid space with ultra-thin flexible endoscope and endoscopic fenestration of scars and adhesions. Thecalopscopy was used in Russian neurosurgery at the first time. Since 2009 we operated 32 patients with following diagnosis: 17--spinal adhesive arachnoiditis (8--local forms, 9--diffuse forms), 12--spinal arachnoid cysts (7--posstraumatic cysts, 5--idiopathic cysts), 3--extramedullary tumors (thecaloscopic videoassistance and biopsy). In all cases we realized exploration of subarachnoid space and pathologic lesion with endoscopic perforation of cyst or dissection of adhesions using special instrumentation. Mean follow-up in our group was 11.4 months. Neurological improvement (mean 1.4 by modified Frankel scale, 1.8 by Ashworth spasticity scale) was seen in 87% of patients operated for spinal arachnopathies. Temporary neurological deterioration (mild disturbances of deep sensitivity) was seen in 9% of patients and managed successfully with conservative treatment. 1 (3.1%) patient was operated 3 times because of relapse of adhesions. There were no serious intraoperative complications (e.g., serious bleeding, dura perforation etc). Postoperative complications included 1 CSF leakage and 1 postoperative neuralgic pain. Mean term of hospitalization was 7.6 days. According to our data, we suppose that thecaloscopy is efficient and safe method, and should be widely used for spinal arachnopaties, adhesive arachnoiditis and arachnoid cysts. Taking into account that adhesive spinal arachnoiditis is systemic process and spinal arachnoid cysts can be extended as well, thecaloscopy may be regarded as the most radical and less-invasive way of surgical treatment existing currently in neurosurgery.
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PMID:[Flexible endoscopy in surgical treatment of spinal adhesive arachnoiditis and arachnoid cysts]. 2456 85

The authors report an unusual case of intrathecal baclofen withdrawal due to the perforation and subsequent leakage of a baclofen pump catheter in a patient with spastic cerebral palsy. A 15-year-old boy underwent an uncomplicated placement of an intrathecal baclofen pump for the treatment of spasticity due to cerebral palsy. After excellent control of symptoms for 3 years, the patient presented to the emergency department with increasing tremors following a refill of his baclofen pump. Initial evaluation consisted of radiographs of the pump and catheter, which appeared normal, and a successful aspiration of CSF from the pump's side port. A CT dye study revealed a portion of the catheter directly overlying the refill port and extravasation of radiopaque dye into the subfascial pocket anterior to the pump. During subsequent revision surgery, a small puncture hole in the catheter was seen to be leaking the drug. The likely cause of the puncture was an inadvertent perforation of the catheter by a needle during the refilling of the pump. This case report highlights a unique complication in a patient with an intrathecal baclofen pump. Physicians caring for these patients should be aware of this rare yet potential complication in patients presenting with baclofen withdrawal symptoms.
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PMID:Baclofen pump catheter leakage after migration of the abdominal catheter in a pediatric patient with spasticity. 2604 90

A paradigm shift is currently ongoing in the treatment of spasticity in childhood in Japan. Functional posterior rhizotomy (FPR), which was first introduced to Japan in 1996, is best indicated for children with spastic cerebral palsy, regardless of the clinical severity of spasticity. Surgery is generally carried out in the cauda equina, where the posterior root is separated from the anterior one, and neurophysiological procedures are used to judge which nerve root/rootlet should be cut. The outcome of FPR is favorable for reducing spasticity in the long-term follow-up. Intrathecal baclofen (ITB) treatment for childhood spasticity was approved in 2007 in Japan and the number of children undergoing ITB pump implantation has been gradually increasing. ITB treatment is best indicated for children with severe spasticity, especially those with dystonia, regardless of the pathological background. Since it is a surgery performed to implant foreign bodies, special attention should be paid to avoid perioperative complications such as CSF leakage, meningitis, and mechanical failure. Severely disabled children with spasticity would benefit most from ITB treatment. We would especially like to emphasize the importance of a strategic approach to the treatment of childhood spasticity. The first step is to reduce spasticity by FPR, ITB, and botulinum toxin injection. The second step is to aim for functional improvement after controlling spasticity. Traditional orthopedic surgery and neuro-rehabilitation form the second step of treatment. The combination of these treatments that allows them to complement each other is the key to a successful treatment of childhood spasticity.
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PMID:Neurosurgical Management of Childhood Spasticity: Functional Posterior Rhizotomy and Intrathecal Baclofen Infusion Therapy. 2622 57

OBJECT Intrathecal baclofen (ITB) is an effective management option for childhood hypertonia. Given the potential complications of implanted ITB pumps, trials of ITB are usually performed as part of the workup for ITB pumps. Two methods are used for ITB trials, lumbar puncture (LP) and catheter insertion into the intrathecal space. Little has been written to date on the number of positive trials and complications in trials. This study aimed to report the outcomes and complications in ITB trials for childhood hypertonia (dystonia, spastic, or mixed). METHODS A retrospective case notes review was conducted of all patients who underwent ITB trials at the Evelina London Children's Hospital between 2005 and 2012 (inclusive). Positive trials were defined as a reduction in Modified Ashworth Scale by a minimum of 1 point in at least 2 muscle groups and improvement reported by the caregivers in the areas of goals agreed upon between professionals and the families. RESULTS Our patient group comprised children with dystonia (n = 7), mixed spasticity/dystonia (n = 29), spasticity (n = 4), and pain (n = 1). A total of 47 trials were attempted in 41 children. Forty trials were successfully completed, with 39 being positive. Thirty-three were catheter trials, and 14 were LPs. The overall complication rate in the 47 attempted trials was 53%: 61% in catheter trials, and 36% in LP trials. This difference was not statistically significant. The most common complications were vomiting (n = 9) and CSF leak (n = 4). The most serious complication was meningitis (n = 1) in a catheter trial. No patients experienced a permanent injury. CONCLUSIONS There is a high risk of minor self-limiting complications with ITB trials, which needs to be factored into the decision process of progression to trials. The rate of positive trials in this study was 98%, of which 21% did not progress to pump implantation. While the authors would still advocate for ITB trials prior to ITB pump insertion to aid parental decision-making, this figure suggests that with good patient selection, ITB pumps could be placed without a preceding trial.
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PMID:Intrathecal baclofen trials: complications and positive yield in a pediatric cohort. 2651 61

OBJECT Intrathecal baclofen (ITB) is a valuable therapeutic option for patients with spasticity and dystonia. The techniques that place an ITB pump catheter into the subcutaneous fat of a lumbar incision are well described. Because patients who require ITB often have low body fat content, they may be predisposed to catheter-related complications. The senior author used a novel technique to place the catheter in a paraspinal subfascial fashion, and the short-term results were previously published. That study demonstrated no development of hardware erosions, catheter migrations, or CSF leaks within an average follow-up of 5 months. This study followed up on those initial findings by looking at the long-term outcomes since this technique was introduced. METHODS Using the institutional review board-approved protocol, the electronic medical records were reviewed retrospectively for all patients who underwent paraspinal subfascial catheter placement by the senior author. Patients received follow-up with the surgeon at 2 weeks postoperatively and were followed routinely by their physiatrist thereafter. RESULTS Of the 43 patients identified as having undergone surgery by the senior author using the paraspinal subfascial technique between July 2010 and February 2014, 12 patients (27.9%) required reoperation. There were 5 patients (11.6%) who had complications related to the catheter or lumbar incision. No hardware erosions or CSF leaks were identified. These patients received a median follow-up of 3.0 years, with 30 of 43 patients receiving follow-up over 2.0 years. CONCLUSION This follow-up study suggests that the technique of paraspinal subfascial catheter placement translates to long-term decreases in CSF leakage and complications from erosion, infection, and also catheter malfunctions. It does not seem to affect the overall rate of complications.
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PMID:Long-term follow-up for lumbar intrathecal baclofen catheters placed using the paraspinal subfascial technique. 2658 57

Repeated replacement of sulphamidase via cerebrospinal fluid injection is an effective treatment for pathological changes in the brain in mice and dogs with the lysosomal storage disorder, mucopolysaccharidosis type IIIA (MPS IIIA). Investigational trials of this approach are underway in children with this condition, however, infusions require attendance at a specialist medical facility. We sought to comprehensively evaluate the effectiveness of sustained-release (osmotic pump-delivered) enzyme replacement therapy in murine MPS IIIA as this method, if applied to humans, would require only subcutaneous administration of enzyme once the pump was installed. Six-week-old MPS IIIA and unaffected mice were implanted with subcutaneous mini-osmotic pumps connected to an infusion cannula directed at the right lateral ventricle. Either recombinant human sulphamidase or vehicle were infused over the course of 7 weeks, with pumps replaced part-way through the experimental period. We observed near-normalisation of primarily stored substrate (heparan sulphate) in both hemispheres of the MPS IIIA brain and cervical spinal cord, as determined using tandem mass spectrometry. Immunohistochemistry indicated a reduction in secondarily stored GM 3 ganglioside and neuroinflammatory markers. A bias towards the infusion side was seen in some, but not all outcomes. The recombinant enzyme appears stable under pump-like conditions for at least 1 month. Given that infusion pumps are in clinical use in other nervous system disorders, e.g. for treatment of spasticity or brain tumours, this treatment method warrants consideration for testing in large animal models of MPS IIIA and other lysosomal storage disorders that affect the brain. Clinical trials of repeated injection of replacement enzyme into CSF are underway in patients with the inherited neurodegenerative disorder mucopolysaccharidosis type IIIA. In this pre-clinical study, we examined an alternative approach - slow, continual infusion of enzyme using pumps. We observed significant reductions in substrate accumulation and other disease-based lesions in treated mouse brain. Thus, the strategy warrants consideration for testing in large animal models of MPS IIIA and also in other neurodegenerative lysosomal storage disorders.
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PMID:Low-dose, continuous enzyme replacement therapy ameliorates brain pathology in the neurodegenerative lysosomal disorder mucopolysaccharidosis type IIIA. 2676 78

OBJECTIVE Intrathecal baclofen infusion systems to manage severe spasticity and dystonia are associated with higher infection rates in children than in adults. Factors unique to this population, such as poor nutrition and physical limitations for pump placement, have been hypothesized as the reasons for this disparity. The authors assessed potential risk factors for infection in a multivariate analysis. METHODS Patients who underwent implantation of a programmable pump and intrathecal catheter for baclofen infusion at a single center between January 1, 2000, and March 1, 2012, were identified in this retrospective cohort study. The primary end point was infection. Potential risk factors investigated included preoperative (i.e., demographics, body mass index [BMI], gastrostomy tube, tracheostomy, previous spinal fusion), intraoperative (i.e., surgeon, antibiotics, pump size, catheter location), and postoperative (i.e., wound dehiscence, CSF leak, and number of revisions) factors. Univariate analysis was performed, and a multivariate logistic regression model was created to identify independent risk factors for infection. RESULTS A total of 254 patients were evaluated. The overall infection rate was 9.8%. Univariate analysis identified young age, shorter height, lower weight, dehiscence, CSF leak, and number of revisions within 6 months of pump placement as significantly associated with infection. Multivariate analysis identified young age, dehiscence, and number of revisions as independent risk factors for infection. CONCLUSIONS Young age, wound dehiscence, and number of revisions were independent risk factors for infection in this pediatric cohort. A low BMI and the presence of either a gastrostomy or tracheostomy were not associated with infection and may not be contraindications for this procedure.
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PMID:Risk factors for baclofen pump infection in children: a multivariate analysis. 2691 15

OBJECTIVE In this single-center study the authors investigated the complications occurring before and after the introduction of the new Ascenda intrathecal catheter (Medtronic Inc.) in pediatric patients treated with intrathecal baclofen therapy (ITB) for spasticity and/or dystonia. METHODS This was a retrospective review of 508 children who had received ITB, 416 with silicone catheters in the 13 years between September 1998 and September 2011 and 92 with Ascenda catheters in the 3 years between September 2011 and August 2014. The authors evaluated major complications such as infections, CSF leaks treated, and problems related to the catheter or pump, and they compared the 2 groups of patients who had received either a silicone catheter or an Ascenda catheter implant. RESULTS One hundred twenty patients in the silicone group (29%) and 1 patient in the Ascenda group (1.1%; p < 0.001) had a major complication. In the silicone group 23 patients (5.5%) were affected by CSF leakage and 75 patients (18%) experienced 82 catheter-related events, such as occlusion, dislodgment, disconnection, or breakage, which required catheter replacement. In the Ascenda group, only 1 patient (1.1%) was affected by CSF leakage. CONCLUSIONS To the authors' knowledge, this study is the first in the literature to compare the performance of the new Ascenda catheter, introduced in 2011, with the traditional silicone catheter for intrathecal drug infusion. In their analysis, the authors found that the Ascenda catheter can reduce major complications related to the catheter after ITB pump implantation. Further investigation is necessary to expand on and confirm their results.
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PMID:Comparison between an Ascenda and a silicone catheter in intrathecal baclofen therapy in pediatric patients: analysis of complications. 2734 10

OBJECTIVE Medically refractory spasticity and dystonia are often alleviated with intrathecal baclofen (ITB) administration through an indwelling catheter inserted in the lumbar spine. In patients with cerebral palsy, however, there is a high incidence of concomitant neuromuscular scoliosis. ITB placement may be technically challenging in those who have severe spinal deformity or who have undergone prior instrumented thoracolumbar fusion. Although prior reports have described drilling through the lumbar fusion mass with a high-speed bur, as well as IT catheter implantation at the foramen magnum or cervical spine, these approaches have notable limitations. To the authors' knowledge, this is the first report of ITB placement using cone beam CT (CBCT) image guidance to facilitate percutaneous IT catheterization. METHODS Data were prospectively collected on patients treated between November 2012 and June 2014. In the interventional radiology suite, general anesthesia was induced and the patient was positioned prone. Imaging was performed to identify the optimal trajectory. Percutaneous puncture was performed at an entry site with image-guided placement of a sheathed needle. CBCT provided real-time 2D projections and 3D reconstructions for detailed volumetric imaging. A biopsy drill was passed through the sheath, and subsequently a Tuohy needle was advanced intrathecally. The catheter was threaded cephalad under fluoroscopic visualization. After tip localization and CSF flow were confirmed, the stylet was replaced, the external catheter tubing was wrapped sterilely in a dressing, and the patient was transported to the operating room. After lateral decubitus positioning of the patient, the IT catheter was exposed and connected to the distal abdominal tubing with typical pump placement. RESULTS Of 15 patients with Gross Motor Function Classification System Levels IV and V cerebral palsy and instrumented thoracolumbar fusion, 8 had predominantly spasticity, and 7 had mixed spasticity and dystonia. The mean age of patients was 20.1 years (range 13-27 years). Nine patients underwent initial catheter and pump placement, and 6 underwent catheter replacement. The procedure was technically successful, with accurate spinal catheter placement in all patients. The median hospital stay was 4 days (IQR 3-5 days). One patient had an early postoperative urinary tract infection. With a mean follow-up of 25.8 months (median 26, range 18-38 months), no CSF leakage or catheter failure occurred. One late infection due to Pseudomonas aeruginosa (requiring pump explantation) occurred at 4 months, probably secondary to recurrent urinary tract infections. CONCLUSIONS Image-guided CBCT navigation resulted in accurate percutaneous placement of the IT catheter for ITB pumps in patients with prior instrumented thoracolumbar fusion. The multimodality approach is an alternate technique that may be used for IT catheter insertion in patients with complex lumbar spine anatomy, extending the potential to provide safe, durable ITB therapy in this population.
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PMID:Image-guided intrathecal baclofen pump catheter implantation: a technical note and case series. 2815 8


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