Daniel S. Kanter

Apolipoprotein E ε4 Is Associated With the Presence and Earlier Onset of Hemorrhage in Cerebral Amyloid Angiopathy

Background and Purpose Cerebral amyloid angiopathy is an important cause of intracerebral hemorrhage in the elderly. The e4 allele of the apolipoprotein E gene, recently established as a genetic risk for Alzheimers disease, has also been suggested as a possible risk factor for cerebral amyloid angiopathy. We sought to determine whether this allele is specifically associated with hemorrhages related to amyloid angiopathy and whether it correlates with the age at which first amyloid angiopathy-related hemorrhage occurs. Methods Forty-five consecutive patients presenting with lobar hemorrhage were prospectively classified according to clinical, radiological, and when available, pathological features and evaluated for apolipoprotein E genotype. They were compared with 1899 elderly patients from a population-based sample and with 18 consecutive patients with hemorrhages in deep regions typical of a hypertensive mechanism. Results Patients with multiple hemorrhages confined to the lobar territory demonstrated ...

Combined Intravenous and Intra-Arterial Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke

Background and Purpose A retrospective analysis was performed on 20 consecutive patients who presented with severe acute ischemic stroke and were evaluated for a combined intravenous (IV) and local intra-arterial (IA) recombinant tissue plasminogen activator (rtPA) thrombolytic approach within 3 hours of onset. Methods Twenty consecutive patients with carotid artery distribution strokes were evaluated and treated using a combined IV and IA rtPA approach over a 14-month period (September 1998 to October 1999). rtPA (0.6 mg/kg) was given intravenously (maximum dose 60 mg); 15% of the IV dose was given as bolus, followed by a continuous infusion over 30 minutes. A maximal IA dose, up to 0.3 mg/kg or 24 mg, whichever was less, was given over a maximum of 2 hours. IV treatment was initiated within 3 hours in 19 of 20 patients. All 20 patients underwent angiography, and 16 of 20 patients received local IA rtPA. Results The median baseline National Institutes of Health Stroke Scale (NIHSS) score for the 20 patients was 21 (range 11 to 31). The median time from stroke onset to IV treatment was 2 hours and 2 minutes, and median time to initiation of IA treatment was 3 hours and 30 minutes. Ten patients (50%) recovered to a modified Rankin Scale (mRS) of 0 or 1; 3 patients (15%), to an mRS of 2; and 5 patients (25%), to an mRS of 4 or 5. One patient (5%) developed a symptomatic intracerebral hemorrhage and eventually died. One other patient (5%) expired because of complications from the stroke. Conclusions We believe that the greater-than-expected proportion of favorable outcomes in these patients with severe ischemic stroke reflects the short time to initiation of both IV and IA thrombolysis.

Plasmapheresis in fulminant acute disseminated encephalomyelitis

Article abstract-We describe two patients with fulminant acute disseminated encephalomyelitis (ADEM) treated with plasmapheresis after they failed to improve on steroids. Both patients improved concomitant with the plasma exchange. These are the first reported cases of fulminant ADEM with extensive white matter abnormalities on imaging studies treated with a regimen of plasmapheresis and steroids. Plasmapheresis may be beneficial in this disorder. NEUROLOGY 1995;45: 824-827

Bilirubin Production and Oxidation in CSF of Patients with Cerebral Vasospasm after Subarachnoid Hemorrhage

Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) remains a significant cause of mortality and morbidity; however, the etiology is, as yet, unknown, despite intensive research efforts. Research in this laboratory indicates that bilirubin and oxidative stress may be responsible by leading to formation of bilirubin oxidation products (BOXes), so we investigated changes in bilirubin concentration and oxidative stress in vitro, and in cerebral spinal fluid (CSF) from SAH patients. Non-SAH CSF, a source of heme oxygenase I (HO-1), and blood were incubated, and in vitro bilirubin production measured. Cerebrospinal fluid from SAH patients was collected, categorized using stimulation of vascular smooth muscle metabolism in vitro, and information obtained regarding occurrence of vasospasm in the patients. Cerebral spinal fluid was analyzed for hemoglobin, total protein and bilirubin, BOXes, malonyldialdehyde and peroxidized lipids (indicators of an oxidizing environment), and HO-1 concentration. The formation of bilirubin in vitro requires that CSF is present, as well as whole, non-anti-coagulated blood. Bilirubin, BOXes, HO-1, and peroxidized lipid content were significantly higher in CSF from SAH patients with vasospasm, compared with nonvasospasm SAH CSF, and correlated with occurrence of vasospasm. We conclude that vasospasm may be more likely in patients with elevated BOXes. The conditions necessary for the formation of BOXes are indeed present in CSF from SAH patients with vasospasm, but not CSF from SAH patients without vasospasm.

A Description of Canadian and United States Physician Reimbursement for Thrombolytic Therapy Administration in Acute Ischemic Stroke

Background and Purpose— Acute ischemic stroke patients are infrequently treated with rtPA, despite its proven effectiveness. Poor physician reimbursement for acute stroke care is one possible explanation for the low frequency of use. We describe the physician reimbursement for thrombolytic therapy for the stroke team physicians serving the Greater Cincinnati/Northern Kentucky region (GCNK), and the Alberta region. Methods— GCNK: billing logs were accessed for the study period of 7/01–12/02, and cross-matched to stroke call logs. University of Calgary (UC): treatment records of a single physician were reviewed from 4/02–3/04. A telephone survey of Canadian provinces was conducted regarding billing practices. Results— GCNK: During the study period, 151 patients received rtPA. For treated pts. the average time spent was 2.6 hours, and average reimbursement received was

Review of Thromboelastography in Neurocritical Care

472 (of those with insurance). The highest reimbursement was received by billing critical care codes. Reimbursement for critical care was similar to or lower than common office procedures for neurologists. UC: during the study period, 131 patients received rtPA. Average reimbursement for rtPA treated patients was

Ultrasound assisted clot lysis for stroke therapy

340 US, not including on-call payments. Survey across Canada revealed many provinces with weekend/after hour premium stipends and on-call stipends. Conclusions— Physician reimbursement for the evaluation and treatment of acute stroke, when compared with other diagnoses commonly treated by neurologists, is relatively low in both the U.S. and Canada. Health policy decision-makers in the US and Canada should be made aware of the importance of providing a more balanced plan to provide medical care to stroke patients.

Stiff-arm syndrome

Thromboelastography (TEG), first described in Germany in 1948 by Dr. Hellmutt Hartert, is a test of the viscoelastic properties of whole blood, providing real-time analysis of hemostasis with information on the kinetics of clot formation and stability, from the initial thrombin burst to fibrinolysis. TEG measures many components of hemostasis (cellular, humoral, and fibrinolysic), identifying both hypocoagulable and hypercoagulable states, thereby facilitating targeted transfusion strategies [1]. TEG has been extensively studied and is commonly used in trauma, liver transplant surgery, cardiac surgery, obstetrics, bedside extracorporeal membrane oxygenation (ECMO) management, diagnosis of hypercoagulable states, major surgeries, hemophilia, and monitoring of antiplatelet therapy [2–4]. Point of care (POC) coagulation monitoring with thromboelastometry, which is similar to TEG as described below, has been shown to reduce the transfusion rate as well as costs in liver transplantation, cardiovascular surgery, and trauma surgery [5–7]. Its use in neurocritical care (NCC) disease processes is expanding, but still largely investigational; this paper reviews the current literature of TEG in NCC. Currently, there are two viscoelastic hemostatic assay (VHAs) systems commercially available: (1) TEG (TEG , Hemoscope Corporation, Niles, IL), which is the most frequently described and prevalent system in North American, and (2) rotational thromboelastometry (ROTEM ; Tem International GmbH, Munich, Germany). A third technology, Sonoclot, similar to TEG but relying on ultrasound, is more specific to platelet function and less well studied in critical care [8]. This review will specifically discuss studies regarding TEG since at the present time—the vast majority of VHA evidence in NCC utilizes TEG Table 1.

Primary prevention of stroke

Thrombolytics such as tissue plasminogen activator (tPA) have advanced the treatment of ischemic stroke. To aid in the development of a transcranial ultrasound thrombolysis system (TUTS), the synergistic thrombolytic effect of tissue plasminogen activator (tPA) and 1‐MHz ultrasound was assessed in vitro in a porcine clot model. Thirty clots were made by incubating 2‐ml aliquots of citrated whole pig blood with 2 μl of bovine thrombin (1 NIH Unit/μl) at 37 °C for 3 h, refrigerated overnight, blotted, and weighed. Clots were placed in an acoustically transparent latex sample holder filled with porcine fresh frozen plasma and tPA at a clinically relevant concentration of 0.0126 mg/ml. The clots were either sham exposed to ultrasound (0.0‐atm amplitude) or exposed to 1‐MHz pulsed ultrasound over a range of duty cycles (10%–100%) at two amplitudes (1.9 and 11.4 atm) for 30 min in a 37 °C water bath, and were weighed to determine the efficacy of thrombolysis. Clots that received continuous wave ultrasound treatment exhibited significantly more thrombolysis than those that were sham exposed (p=0.001, students t‐test). The TUTS technology promises to improve the effectiveness of thrombolytic drugs so that ultimately lower concentrations of drugs can be used for faster recanalization of blocked arteries. [Work supported by The Neuroscience Institute, University of Cincinnati Medical Center.]

Thrombolytic Therapy for Pulmonary Embolism: Frequency of Intracranial Hemorrhage and Associated Risk Factors

A 56-year-old woman experienced progressive stiffness and painful spasms in the right arm leading to a frozen arm within 2 years. She had previously developed cerebellar ataxia (anti–glutamic acid decarboxylase [GAD] antibodies, 1,550 nmol/L; age 52 years). Examination showed marked rigidity and decreased movement range of the right arm with generalized hyperreflexia (figure and video). There were no antiamphiphysin or other paraneoplastic antibodies. Search for malignancies was negative. Diabetes was ruled out. The patient benefited from diazepam and IV immunoglobulin. Stiff-person syndrome (SPS) affects predominantly the trunk and lower limbs.1 This case illustrates that the cerebellar ataxia-SPS spectrum of anti-GAD autoimmunity may occur sequentially rather than concurrently, and a stiff arm, a variant of paraneoplastic SPS,2 may rarely be a focal form of anti-GAD-mediated (nonparaneoplastic) SPS.