warfarin and Movement-Disorders

Future demographic changes predict an increase in the number of patients with atrial fibrillation. As long-term anticoagulation for the prevention of ischemic strokes becomes more prevalent, the burden of warfarin-associated intracerebral hemorrhage (W-ICH) is likely to grow. However, little is known about the clinical aspects and pathophysiologic mechanisms of W-ICH. This study describes the development of a mouse model of W-ICH in which hematoma growth and outcomes can be correlated with anticoagulation parameters.. CD-1 mice were treated with warfarin (2 mg/kg per 24 hours) added to drinking water. ICH was induced by stereotactic injection of collagenase type VII (0.075 U) into the right striatum. Hemorrhagic blood volume was quantified by means of a photometric hemoglobin assay 2 and 24 hours after hemorrhage induction. Neurologic outcomes were assessed on a 5-point scale.. The international normalized ratio in nonanticoagulated mice was 0.8+/-0.1. After 24 (W-24) and 30 (W-30) hours of warfarin pretreatment, international normalized ratio values increased to 3.5+/-0.9 and 7.2+/-3.4, respectively. Compared with nonanticoagulated mice, mean hemorrhagic blood volume determined 24 hours after hemorrhage induction was found to be 2.5-fold larger in W-24 mice (P=0.019) and 3.1-fold larger in W-30 mice (P<0.001, n=10 per group). Mortality at 24 hours after hemorrhage induction was 0% in nonanticoagulated mice, 10% in W-24 mice, and 30% in W-30 mice. Hematoma enlargement between 2 and 24 hours after hemorrhage induction was -1.4% for nonanticoagulated mice, 22.9% for W-24 mice, and 62.2% for W-30 mice.. This study characterizes the first experimental model of W-ICH. It may be helpful in gaining further insights into the pathophysiology of W-ICH and may be used for testing the efficacy of treatment strategies, such as hemostatic therapy, in this severe subtype of stroke.

Topics: Administration, Oral; Animals; Anticoagulants; Brain Damage, Chronic; Cerebral Hemorrhage; Collagenases; Corpus Striatum; Disease Models, Animal; Disease Progression; Hematoma; Injections; International Normalized Ratio; Male; Mice; Microbial Collagenase; Movement Disorders; Warfarin

Movement disorders have only rarely been reported in association with antiphospholipid syndrome (APS). In such cases, chorea is the most common disorder observed, with occasional reports of hemidystonia, Parkinsonism, and hemiballism. We report here on 3 cases of APS (3 women ages 16, 46, and 56 years) who presented with movement disorders, including tics, tremor, myoclonus, and a corticobasal syndrome, never or rarely reported in association with this disease. Mild executive dysfunction was observed in all 3 patients. We also report the successful treatment of two of these patients with mild oral anticoagulation (INR 2-3). Movement disorders in APS seem more clinically heterogeneous than previously thought. Oral anticoagulation should be considered in the treatment of movement disorders associated with APS.

Topics: Adolescent; Antiphospholipid Syndrome; Brain; Cerebral Infarction; Diagnosis, Differential; Dyskinesias; Electroencephalography; Electromyography; Female; Follow-Up Studies; Frontal Lobe; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Middle Aged; Movement Disorders; Myoclonus; Neurologic Examination; Neuropsychological Tests; Occipital Lobe; Phenindione; Phenprocoumon; Sneddon Syndrome; Spinocerebellar Degenerations; Tics; Tourette Syndrome; Tremor; Warfarin