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https://www.readbyqxmd.com/read/28920889/therapies-targeting-dna-and-rna-in-huntington-s-disease
#1
REVIEW
Edward J Wild, Sarah J Tabrizi
No disease-slowing treatment exists for Huntington's disease, but its monogenic inheritance makes it an appealing candidate for the development of therapies targeting processes close to its genetic cause. Huntington's disease is caused by CAG repeat expansions in the HTT gene, which encodes the huntingtin protein; development of therapies to target HTT transcription and the translation of its mRNA is therefore an area of intense investigation. Huntingtin-lowering strategies include antisense oligonucleotides and RNA interference targeting mRNA, and zinc finger transcriptional repressors and CRISPR-Cas9 methods aiming to reduce transcription by targeting DNA...
October 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28919982/effective-management-of-spasticity-and-impacts-on-weight-change-and-resting-energy-expenditure-in-a-female-with-spinal-cord-injury-a-case-report
#2
Amy N Nevin, Khanh Nguyen, Sridhar Atresh, Angela Vivanti, Ingrid J Hickman
INTRODUCTION: The impact of muscle spasticity on weight change and energy expenditure after spinal cord injury (SCI) is not well understood. CASE PRESENTATION: This case study reports changes to body weight and resting energy expenditure (REE) in a 36-year-old female (T3 AIS A SCI; 80 kg; body mass index=28 kg m(-)(2) at injury) requiring escalating therapies to manage severe spasticity. Body weight, spasticity medications and fasted REE (measured using indirect calorimetry, canopy hood) were recorded at 4, 16, 17, 20 and 44 months post injury...
2017: Spinal Cord Series and Cases
https://www.readbyqxmd.com/read/28915338/neurocognitive-psychosocial-and-quality-of-life-outcomes-in-adult-survivors-of-childhood-non-hodgkin-lymphoma
#3
Matthew J Ehrhardt, Daniel A Mulrooney, Chenghong Li, Malek J Baassiri, Kari Bjornard, John T Sandlund, Tara M Brinkman, I-Chan Huang, Deo Kumar Srivastava, Kirsten K Ness, Leslie L Robison, Melissa M Hudson, Kevin R Krull
BACKGROUND: Children with non-Hodgkin lymphoma (NHL) undergo treatment with central nervous system-directed therapy, the potentially neurotoxic effects of which have not been reported in NHL survivors. METHODS: NHL survivors (n = 187) participating in the St. Jude Lifetime Cohort who were 10 or more years from their diagnosis and were 18 years old or older underwent neurocognitive, emotional distress (Brief Symptom Inventory 18), and health-related quality of life (HRQOL) assessments (36-Item Short Form Health Survey)...
September 15, 2017: Cancer
https://www.readbyqxmd.com/read/28913765/treatment-of-theiler-s-virus-induced-demyelinating-disease-with-teriflunomide
#4
Francesca Gilli, Libin Li, Darlene B Royce, Krista D DiSano, Andrew R Pachner
Teriflunomide is an oral therapy approved for the treatment of relapsing remitting multiple sclerosis (MS), showing both anti-inflammatory and antiviral properties. Currently, it is uncertain whether one or both of these properties may explain teriflunomide's beneficial effect in MS. Thus, to learn more about its mechanisms of action, we evaluated the effect of teriflunomide in the Theiler's encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a viral infection and an excellent model of the progressive disability of MS...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28913502/regional-anesthesia-for-a-total-knee-arthroplasty-on-an-adult-patient-with-spastic-diplegia-and-an-intrathecal-baclofen-pump
#5
Elird Bojaxhi, David R Salek, Courtney E Sherman, Roy A Greengrass
We describe the clinical presentation of a patient with spastic diplegia, and its unique perioperative challenges. Opioids and antispasmodic medications are the primary therapy for managing pain and spasticity in the perioperative setting. However, such combination results in several side-effects and their sedative properties are synergistic. A 64-year-old woman with a history of spastic diplegia and an intrathecal baclofen pump for the treatment of her lower extremity spasticity was scheduled for a third elective left knee arthroplasty...
April 2017: Rom J Anaesth Intensive Care
https://www.readbyqxmd.com/read/28890435/pain-control-in-thoracic-oncology
#6
Christine Peeters-Asdourian, Gilbert Massard, Paragi H Rana, Paul Van Houtte, Andrew P White, Bogdan Grigoriu, Dominique Lossignol, Mohammed Almalki, Jean Alexiou, Jean-Luc Engelholm, Jean-Paul Sculier
This review of pain management in lung cancer is based on the presentation of four cases of thoracic oncology patients with pain at various stages of their disease. The approach will be multidisciplinary, involving a thoracic oncologist, radiologist, thoracic and orthopaedic spine surgeon, radiation therapist, pain medicine specialist, and palliative care specialist. This multispecialty approach to the management of different painful presentations in thoracic oncology will demonstrate the complexity of each case and the improved patient outcomes which result from the involvement of different disciplines working in concert...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28889721/spinal-myoclonus-responding-to-continuous-intrathecal-morphine-pump
#7
Jung-Eun Ahn, Dallah Yoo, Ki-Young Jung, Jong-Min Kim, Beom Seok Jeon, Myung Chong Lee
Spinal myoclonus is a sudden, brief, and involuntary movement of segmental or propriospinal muscle groups. Spinal myoclonus has occasionally been reported in patients undergoing opioid therapy, but the pathophysiology of opioid-induced myoclonus has not been elucidated yet. Here, we present two patients with spinal segmental myoclonus secondary to ischemic and radiation myelopathy. Conventional medications did not help treat persistent myoclonus in both legs. Continuous intrathecal morphine infusion was implanted for pain control in one patient, which relieved spinal myoclonus entirely...
September 12, 2017: Journal of Movement Disorders
https://www.readbyqxmd.com/read/28883219/high-dose-chemotherapy-with-autologous-stem-cell-transplantation-following-systemic-chemotherapy-prophylactic-intrathecal-methotrexate-and-radiotherapy-prevents-relapse-and-improves-the-outcome-of-advanced-stage-primary-testicular-lymphoma-even-with-cardiac
#8
Shin Lee, Takahiro Yamauchi, Keiichi Kinoshita, Shin Imamura, Kenichi Kamiya
Primary testicular lymphoma (PTL) is a rare but aggressive disease. Although most patients present in the early stage, their prognosis is poor. Similar with PTL, cardiac lymphoma is also an uncommon disease characterized by its aggressive clinical course and poor prognosis. We herein report an extremely rare case of advanced stage PTL with cardiac involvement, treated by high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT) followed by systemic chemotherapy, prophylactic intrathecal methotrexate (IT-MTX), and radiotherapy...
September 6, 2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28874182/long-term-neurologic-and-cardiac-correction-by-intrathecal-gene-therapy-in-pompe-disease
#9
J Hordeaux, L Dubreil, C Robveille, J Deniaud, Q Pascal, B Dequéant, J Pailloux, L Lagalice, M Ledevin, C Babarit, P Costiou, F Jamme, M Fusellier, Y Mallem, C Ciron, C Huchet, C Caillaud, M-A Colle
Pompe disease is a lysosomal storage disorder caused by acid-α-glucosidase (GAA) deficiency, leading to glycogen storage. The disease manifests as a fatal cardiomyopathy in infantile form. Enzyme replacement therapy (ERT) has recently prolonged the lifespan of these patients, revealing a new natural history. The neurologic phenotype and the persistence of selective muscular weakness in some patients could be attributed to the central nervous system (CNS) storage uncorrected by ERT. GAA-KO 6neo/6neo mice were treated with a single intrathecal administration of adeno-associated recombinant vector (AAV) mediated gene transfer of human GAA at 1 month and their neurologic, neuromuscular, and cardiac function was assessed for 1 year...
September 6, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28868047/in-premature-newborns-intraventricular-hemorrhage-causes-cerebral-vasospasm-and-associated-neurodisability-via-heme-induced-inflammasome-mediated-interleukin-1-production-and-nitric-oxide-depletion
#10
Michael Eisenhut, Samyami Choudhury
BACKGROUND: Intraventricular hemorrhage (IVH) occurs in 60-70% of neonates weighing 500-750 g and 10-20% of those weighing 1,000-1,500 g. All forms of IVH have been associated with neurocognitive deficits. Both subarachnoid and IVHs have been associated with delayed vasospasm leading to neurological deficits. Pathways linking hemoglobin release from blood clots to vasospasm include heme-induced activation of inflammasomes releasing interleukin-1 (IL-1) that can cause calcium dependent and independent vasospasm...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28866663/infections-of-intrathecal-baclofen-delivery-systems-and-ventriculoperitoneal-shunting-systems-clinical-series-discussion
#11
Oussama Abousamra, Maria Del Pilar Duque Orozco, Kenneth J Rogers, Freeman Miller, Julieanne P Sees
BACKGROUND/AIMS: The physiological interaction between the intrathecal baclofen (ITB) delivery system and the ventriculoperitoneal (VP) shunting system in a patient who had both systems implanted has not been reported previously. The aim of our report is to evaluate the effect that one system's infection might have on the other. METHODS: Records of children who were followed at our institution between 2004 and 2015 for management of their ITB systems were reviewed...
September 2, 2017: Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28859883/analgesic-effects-of-novel-lysophosphatidic-acid-receptor-5-antagonist-as2717638-in-rodents
#12
Nobuhito Murai, Hideki Hiyama, Tetsuo Kiso, Toshihiro Sekizawa, Tomonari Watabiki, Hiromasa Oka, Toshiaki Aoki
Lysophosphatidic acid (LPA) is a bioactive lipid that acts via at least six G protein-coupled receptors, LPA receptors 1-6 (LPA1-6), for various physiological functions. We examined (1) whether LPA5 is involved in pain signaling in the spinal cord; and (2) the pharmacological effects of a novel LPA5 antagonist on intrathecal prostaglandin (PG)- and (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced allodynia, and neuropathic and inflammatory pain in rodents. Intrathecal injection of a selective LPA5 agonist, geranylgeranyl diphosphate, and a non-selective agonist, LPA, induced allodynia in wild type, but not in LPA5 knockout mice...
August 30, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28837387/crmp2-is-necessary-for-neurofibromatosis-type-1-related-pain
#13
Aubin Moutal, Song Cai, Shizhen Luo, Raphaëlle Voisin, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases, affecting roughly 1 in 3000 individuals. As a multisystem disorder, it affects cognitive development, as well as bone, nerve and muscle constitution. Peripheral neuropathy in NF1 constitutes a potentially severe clinical complication and is associated with increased morbidity and mortality. The discovery of effective therapies for Neurofibromatosis type 1 (NF1) pain depends on mechanistic understanding that has been limited, in part, by the relative lack of availability of animal models relevant to NF1 pain...
August 24, 2017: Channels
https://www.readbyqxmd.com/read/28835663/choroid-plexitis-and-ependymitis-by-magnetic-resonance-imaging-are-biomarkers-of-neuronal-damage-and-inflammation-in-hiv-negative-cryptococcal-meningoencephalitis
#14
Dima A Hammoud, Eman Mahdi, Anil A Panackal, Paul Wakim, Virginia Sheikh, Irini Sereti, Bibi Bielakova, John E Bennett, Peter R Williamson
CNS cryptococcal meningoencephalitis in both HIV positive (HIV+) and HIV negative (HIV-) subjects is associated with high morbidity and mortality despite optimal antifungal therapy. We thus conducted a detailed analysis of the MR imaging findings in 45 HIV- and 11 HIV+ patients to identify imaging findings associated with refractory disease. Ventricular abnormalities, namely ependymitis and choroid plexitis were seen in HIV- but not in HIV+ subjects. We then correlated the imaging findings in a subset of HIV- subjects (n = 17) to CSF levels of neurofilament light chain (NFL), reflective of axonal damage and sCD27, known to best predict the presence of intrathecal T-cell mediated inflammation...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28834868/outcomes-of-intrathecal-baclofen-therapy-in-patients-with-cerebral-palsy-and-acquired-brain-injury
#15
Young Kwon Yoon, Kil Chan Lee, Han Eol Cho, Minji Chae, Jin Woo Chang, Won Seok Chang, Sung-Rae Cho
Intrathecal baclofen (ITB) has been known to reduce spasticity which did not respond to oral medications and botulinum toxin treatment. However, few results have been reported comparing the effects of ITB therapy in patients with cerebral palsy (CP) and acquired brain injury. This study aimed to investigate beneficial and adverse effects of ITB bolus injection and pump therapy in patients with CP and to compare outcomes to patients with acquired brain injury such as traumatic brain injury and hypoxic brain injury...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28832395/multiple-sites-and-actions-of-gabapentin-induced-relief-of-ongoing-experimental-neuropathic-pain
#16
Kirsty Bannister, Chaoling Qu, Edita Navratilova, Janice Oyarzo, Jennifer Yanhua Xie, Tamara King, Anthony H Dickenson, Frank Porreca
Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats...
August 21, 2017: Pain
https://www.readbyqxmd.com/read/28831736/intravascular-lymphoma-in-the-cns-options-for-treatment
#17
REVIEW
Damir Nizamutdinov, Nitesh P Patel, Jason H Huang, Ekokobe Fonkem
Purpose of review The purpose of this review was to discuss therapeutic manipulations and effective current interventions available to treat intravascular lymphoma in the central nervous system. Recent findings Patients experienced resolution and remission of disease for 14 months and up to 2 years after eight cycles of R-CHOP and four courses of intrathecal therapy with MTX, cytarabine, and prednisolone. Intravascular use of unfractionated heparin during therapy may contribute to better outcome. Summary Series of therapeutic avenues were analyzed and compared...
August 23, 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28822691/fatal-meningitis-in-swine-after-intrathecal-administration-of-adeno-associated-virus-expressing-syngeneic-interleukin-10
#18
Mark D Unger, Josef Pleticha, James E Collins, Anibal G Armien, Jennifer L Brazzell, Laura K Newman, Lukas F Heilmann, Jodi A Scholz, Timothy P Maus, Andreas S Beutler
Interleukin-10 (IL-10) delivered by intrathecal (i.t.) gene vectors is a candidate investigational new drug (IND) for several chronic neurological disorders such as neuropathic pain. We performed a preclinical safety study of IL-10. A syngeneic large animal model was used delivering porcine IL-10 (pIL-10) to the i.t. space in swine by adeno-associated virus serotype 8 (AAV8), a gene vector that was previously found to be nontoxic in the i.t. space. Unexpectedly, animals became ill, developing ataxia, seizures, and an inability to feed and drink, and required euthanasia...
August 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28817499/nurse-practitioner-lead-pediatric-baclofen-pump-program-impact-on-safety-and-quality-of-care
#19
Kristin Buxton, Ann Morgan, Jayne Rogers
Children with cerebral palsy experience spasticity that can be debilitating and cause significant pain and contractures. Intrathecal baclofen (ITB) therapy can help relieve this spasticity and improve the quality of life for these patients, but it comes with risk. Withdrawal from the medication in case of abrupt discontinuation of delivery can be life-threatening. Regular maintenance of the system is mandatory. Having a program in place to manage the device and support patients helps to ensure their safety...
August 16, 2017: Journal of Neuroscience Nursing: Journal of the American Association of Neuroscience Nurses
https://www.readbyqxmd.com/read/28816796/intrathecal-infusion-of-haploidentical-nondonor-lymphocytes-for-central-nervous-system-leukemic-relapse-after-haploidentical-hematopoietic-stem-cell-transplantation
#20
Azusa Mayumi, Akihisa Sawada, Aya Ioi, Kohei Higuchi, Mariko Shimizu, Maho Sato, Masahiro Yasui, Masami Inoue
Leukemic relapse in the central nervous system (CNS) after conventional treatment is associated with a poor prognosis. The effectiveness and safety of IV infusion of human leukocyte antigen (HLA)-mismatched lymphocytes for leukemia, and intrathecal (IT) infusion of HLA-mismatched lymphocytes for cerebrospinal fluid (CSF) dissemination of medulloblastoma have been reported. A 13-year-old girl (HLA-A31) was diagnosed as relapsing from Philadelphia chromosome-positive acute leukemia in the CNS after receiving chemotherapy, tyrosine kinase inhibitors, haploidentical hematopoietic stem cell transplantation (HSCT) from her father (HLA-A31), and craniospinal irradiation...
August 14, 2017: Journal of Pediatric Hematology/oncology
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