warfarin and Nervous-System-Diseases

Topics: Abnormalities, Drug-Induced; Anti-Infective Agents; Anticoagulants; Biomedical Research; Cytochrome P-450 Enzyme System; Drug Eruptions; Drug Interactions; Female; Folic Acid Deficiency; Hematologic Diseases; Hemolysis; Humans; Hyperkalemia; Hypoglycemia; Hypoglycemic Agents; Immunocompromised Host; Infant, Newborn; Infant, Small for Gestational Age; Kidney; Nervous System Diseases; Pregnancy; Trimethoprim, Sulfamethoxazole Drug Combination; Warfarin

Brain injury from stroke and traumatic brain injury (TBI) may result in a persistent neuroinflammatory response in the injury penumbra. This response may include microglial activation and excess levels of tumour necrosis factor (TNF). Previous experimental data suggest that etanercept, a selective TNF inhibitor, has the ability to ameliorate microglial activation and modulate the adverse synaptic effects of excess TNF. Perispinal administration may enhance etanercept delivery across the blood-CSF barrier.. The objective of this study was to systematically examine the clinical response following perispinal administration of etanercept in a cohort of patients with chronic neurological dysfunction after stroke and TBI.. After approval by an independent external institutional review board (IRB), a chart review of all patients with chronic neurological dysfunction following stroke or TBI who were treated open-label with perispinal etanercept (PSE) from November 1, 2010 to July 14, 2012 at a group medical practice was performed.. The treated cohort included 629 consecutive patients. Charts of 617 patients following stroke and 12 patients following TBI were reviewed. The mean age of the stroke patients was 65.8 years ± 13.15 (range 13-97). The mean interval between treatment with PSE and stroke was 42.0 ± 57.84 months (range 0.5-419); for TBI the mean interval was 115.2 ± 160.22 months (range 4-537). Statistically significant improvements in motor impairment, spasticity, sensory impairment, cognition, psychological/behavioural function, aphasia and pain were noted in the stroke group, with a wide variety of additional clinical improvements noted in individuals, such as reductions in pseudobulbar affect and urinary incontinence. Improvements in multiple domains were typical. Significant improvement was noted irrespective of the length of time before treatment was initiated; there was evidence of a strong treatment effect even in the subgroup of patients treated more than 10 years after stroke and TBI. In the TBI cohort, motor impairment and spasticity were statistically significantly reduced.. Irrespective of the methodological limitations, the present results provide clinical evidence that stroke and TBI may lead to a persistent and ongoing neuroinflammatory response in the brain that is amenable to therapeutic intervention by selective inhibition of TNF, even years after the acute injury.. Excess TNF contributes to chronic neurological, neuropsychiatric and clinical impairment after stroke and TBI. Perispinal administration of etanercept produces clinical improvement in patients with chronic neurological dysfunction following stroke and TBI. The therapeutic window extends beyond a decade after stroke and TBI. Randomized clinical trials will be necessary to further quantify and characterize the clinical response.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Brain Injuries; Cohort Studies; Etanercept; Female; Humans; Immunoglobulin G; Injections, Spinal; Male; Middle Aged; Motor Skills; Muscle Spasticity; Nervous System Diseases; Pain Management; Receptors, Tumor Necrosis Factor; Recovery of Function; Sensation; Stroke; Treatment Outcome; Tumor Necrosis Factor-alpha; Walking; Warfarin; Young Adult

Fifty-seven pregnancies in women with antiphospholipid syndrome (APS) are presented. These were treated with s.c. enoxaparin and low dose aspirin. In fourteen pregnancies warfarin was prescribed between weeks 15-34 (warfarin group). The decision to switch to warfarin depended on a morbidity score, and the patient's consent. Neither teratogenicity nor significant maternal, fetal or neonatal hemorrhage was observed. Despite the higher pretreatment morbidity score of the warfarin group, the live birth rate was high in both groups: 86% in the warfarin group and 87% in the non-warfarin group. There was no significant difference in week of delivery, birth weight, or incidence of thrombosis between the groups. The study demonstrates the efficacy and safety of anticoagulants during pregnancy. The use of LMWH in pregnant women with APS not being moot, warfarin might be justified in selected patients.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Autoimmune Diseases; Enoxaparin; Female; Hemorrhage; Humans; Infant, Newborn; Lupus Erythematosus, Systemic; Nervous System Diseases; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy, Multiple; Safety; Thrombosis; Warfarin

As the number of patients with cardioembolic ischemic stroke is predicted to be double by 2030, increased burden of warfarin-associated hemorrhagic transformation (HT) after cerebral ischemia is an expected consequence. However, thus far, no effective treatment strategy is available for HT prevention in routine clinical practice. While the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) is known to protect against oxidative stress and neuronal cell death caused by ischemic brain damage, its effect on preventing warfarin-associated HT after cerebral ischemia is yet unknown. Therefore, we hypothesized that Ex-4 would stabilize the blood-brain barrier (BBB) and suppress neuroinflammation through PI3K-Akt-induced inhibition of glycogen synthase kinase-3β (GSK-3β) after warfarin-associated HT post-cerebral ischemia.. We used male C57BL/6 mice for all experiments. A 5-mg warfarin sodium tablet was dissolved in animals' drinking water (effective warfarin uptake 0.04 mg (2 mg/kg) per mouse). The mice were fed for 0, 6, 12, and 24 h with ad libitum access to the treated water. To study the effects of Ex-4, temporary middle cerebral artery occlusion (MCAO) was performed. Then, either Ex-4 (10 mg/kg) or saline was injected through the tail vein, and in the Ex-4 + wortmannin group, PI3K inhibitor wortmannin was intravenously injected, after reperfusion. The infarct volume, neurological deficits, and integrity of the BBB were assessed 72 h post MCAO. One- or two-way ANOVA was used to test the difference between means followed by Newman-Keuls post hoc testing for pair-wise comparison.. We observed that Ex-4 ameliorated warfarin-associated HT and preserved the integrity of the BBB after cerebral ischemia through the PI3K/Akt/GSK-3β pathway. Furthermore, Ex-4 suppressed oxidative DNA damage and lipid peroxidation, attenuated pro-inflammatory cytokine expression levels, and suppressed microglial activation and neutrophil infiltration in warfarin-associated HT post-cerebral ischemia. However, these effects were totally abolished in the mice treated with Ex-4 + the PI3K inhibitor-wortmannin. The PI3K/Akt-GSK-3β signaling pathway appeared to contribute to the protection afforded by Ex-4 in the warfarin-associated HT model.. GLP-1 administration could reduce warfarin-associated HT in mice. This beneficial effect of GLP-1 is associated with attenuating neuroinflammation and BBB disruption by inactivating GSK-3β through the PI3K/Akt pathway.

Topics: Animals; Anticoagulants; Blood-Brain Barrier; Brain; Brain Infarction; Brain Ischemia; Cytokines; Disease Models, Animal; Exenatide; Gene Expression Regulation; Glucagon-Like Peptide-1 Receptor; Hemorrhage; Hypoglycemic Agents; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred C57BL; Microglia; Nervous System Diseases; Peptides; Signal Transduction; Venoms; Warfarin

The 2009 Golden Helix Symposium on Pharmacogenomics and Personalized medicine was held in Athens, Greece, where approximately 150 participants from 21 countries were updated on recent developments in the fields of pharmacogenetics and pharmacogenomics. The meeting was supported by ten corporate entities, of which three were major pharmaceutical and two were technology companies. It was endorsed by the University of Chicago and partly funded by the University of Patras. Here, we report some highlights of this meeting.

Topics: Anticoagulants; Drug-Related Side Effects and Adverse Reactions; Genetic Variation; Humans; Mental Disorders; Nervous System Diseases; Pharmacogenetics; Polymorphism, Single Nucleotide; Precision Medicine; Warfarin

We hypothesized that patients with cerebral infarction on preadmission warfarin have less severe neurological deficits on admittance, less severe neurological deficits 1 week after the onset of cerebral infarction and a larger improvement as to neurological deficits within 1 week of acute cerebral infarction.. All patients with cerebral infarction who did not receive thrombolytic treatment were included. Preadmission use of warfarin was registered. The National Institute of Health Stroke Scale (NIHSS) score was obtained on admittance and 7 days after stroke onset.. In total, 42 patients (8.1%) used warfarin at the time of stroke onset. The mean NIHSS score on admittance was 6.9 among the patients on warfarin and 5.2 among those without warfarin (p = 0.10). The 1-week improvement in the NIHSS score was 3.5 among the patients on warfarin and 0.8 among the participants without warfarin (p < 0.001). Linear regression showed that a low NIHSS score on day 7 was independently associated with a low NIHSS score on admittance (p < 0.001), low age (p = 0.002) and preadmission use of warfarin (p < 0.001).. Preadmission warfarin was not associated with less severe neurological deficits on admittance. However, it was related to both less severe neurological deficits 1 week after the onset of cerebral infarction and larger improvement as to neurological deficits within 1 week of acute cerebral infarction.

Topics: Acute Disease; Aged; Anticoagulants; Atrial Fibrillation; Cerebral Infarction; Female; Humans; Linear Models; Male; Nervous System Diseases; Norway; Outcome Assessment, Health Care; Prognosis; Prospective Studies; Retrospective Studies; Time Factors; Warfarin

Head CT is frequently ordered for trauma patients who are receiving anticoagulation. However, whether patients with a Glasgow Coma Scale (GCS) score of 15 and normal findings on neurologic examination require CT is still debated. The purpose of our study was to assess the use of cranial CT in patients receiving anticoagulants after head trauma and to establish clinical criteria to identify those in this group who do not need emergency CT.. We retrospectively reviewed patients receiving heparin or coumadin who had head trauma and who subsequently underwent cranial CT at a level I trauma center within a 4-year period. Patients were evaluated for mechanism of injury, clinical signs and symptoms of head injury, and type and reason for anticoagulation. Prothrombin time, international normalized ratio, partial thromboplastin time, GCS score, age, and head CT results were recorded for each patient.. A total of 89 patients fulfilled the enrollment criteria. Among them, 82 had no evidence of intracranial injury on CT. Seven patients had evidence of intracranial hemorrhage. Patients without hemorrhage had no significant focal neurologic deficits and presented with an average GCS score of 14.8. Patients with intracranial hemorrhage tended to have focal neurologic deficits and presented with an average GCS score of 12.0.. Patients with head injury, normal GCS scores, and no focal neurologic deficits and who are receiving the anticoagulants heparin or coumadin may not necessarily require emergency CT.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cerebral Hemorrhage; Craniocerebral Trauma; Female; Glasgow Coma Scale; Heparin; Humans; Male; Nervous System Diseases; Retrospective Studies; Tomography, X-Ray Computed; Warfarin

Facial numbness and dysesthesia have not been emphasized as presenting features in spontaneous internal carotid artery dissection. Progressive facial pain, accompanied by oculosympathetic paresis, altered taste, and facial numbness suggest the possibility of basal skull neoplasm. We describe a patient, with previously undiscovered fibromuscular dysplasia, who presented with severe neck and face pain, dysgeusia, oculosympathetic paresis, and markedly reduced facial sensation due to a spontaneous vascular dissection. Altered facial sensation should now be included in the symptomatology of internal carotid artery dissection.

Topics: Aortic Dissection; Carotid Artery Diseases; Carotid Artery, Internal; Face; Facial Pain; Female; Heparin; Humans; Middle Aged; Nervous System Diseases; Radiography; Sensation; Taste Disorders; Warfarin