Neutralizing antibodies to 500 microg interferon beta-1b: 28-month results of the IDEAS extension trial.

The Interferon Dose Escalation Assessment of Safety extension trial monitored neutralizing antibodies to interferon beta-1b in patients who currently or had previously received the double dose (500 microg) for up to 28 months. Fifteen patients entered the extension trial; five patients were neutralizing antibody-positive at the start of the trial. The present study demonstrates that when neutralizing antibodies develop in patients receiving higher doses of interferon beta-1b they tend to persist for a prolonged period, although neutralizing antibody titers tend to decrease over time and some patients may revert to neutralizing antibody-negative status.

Interferon beta-1b (betaseron/betaferon) is well tolerated at a dose of 500 microg: interferon dose escalation assessment of safety (IDEAS).

The approved interferon beta-1b (Betaseron/Betaferon) dose is 250 microg (8 MIU) administered subcutaneously (sc) every other day (eod). Clinical trial data suggest a dose response effect for interferon beta in multiple sclerosis (MS) treatment and a maximum dose has yet to be established. The Interferon Dose Escalation Assessment of Safety (IDEAS) study evaluated the safety and tolerability of interferon beta-1b 500 microg (16 MIU) sc eod with structured dose escalation and adverse event (AE) management in 22 patients (20 interferon beta-1b-treated (SD) and two interferon beta-1b-naïve (ND)) with relapsing-remitting (RR) MS, secondary-progressive (SP) MS, or progressive relapsing MS. IDEAS comprised an eight-week dose escalation period and a 12-week maintenance period, with modification as clinically warranted. Autoinjectors were used for all injections > or =0.4 mL. Clinical laboratory values were monitored monthly. Baseline and exit assessments included the MS Functional Composite score, EDSS, and neutralizing antibody MxA assay. AEs were recorded at every injection. Dose escalation ranged from two to 12 weeks. Some 91% of patients (20/22) achieved the 500-microg dose, and of these 90% (18/20) completed the maintenance phase. There were no differences in response between ND and SD patients. Most common AEs were decreased general well-being, insomnia, and injection site reactions (mostly mild). The 500-microg dose of interferon beta-1b was well tolerated in the short-term with escalation and premedication in these patients, most of whom had previously been receiving 250 microg interferon beta-1b.

Multiple sclerosis characteristics in African American patients in the New York State Multiple Sclerosis Consortium.

The objective of this study was to determine the clinical characteristics of multiple sclerosis (MS) in African American (AA) patients in the New York State Multiple Sclerosis Consortium (NYSMSC) patient registry. The NYSMSC is a group of 18 MS centers throughout New York State organized to prospectively assess clinical characteristics of MS patients. AAs comprise 6% (329) of the total NYSMSC registrants (5602). Demographics, disease course, therapy, and socioeconomic status were compared in AA registrants versus nonAfrican Americans (NAA). There was an increased female preponderance and a significantly younger age at diagnosis in the AA group. AA patients were more likely to have greater disability with increased disease duration. No differences were seen in types of MS and use of disease modifying therapies. Our findings suggest a racial influence in MS. Further genetic studies that consider race differences are warranted to elucidate mechanisms of disease susceptibility.

A profile of multiple sclerosis: the New York State Multiple Sclerosis Consortium.

We have obtained a current profile of multiple sclerosis York State through a centralized patient registry and standardized data collection instrument associated with the New York State Multiple Sclerosis Consortium of 12 MS centers located throughout the state. Data from the first 3019 patients with clinically definite MS revealed a clear relationship between MS disease type, duration of disease, and severity of physical disability. Patients with relapsing disease had disease durations approximately half as long as those with progressive forms of the disease (means approximately 6 years versus 11 years). The majority of patients with relapsing disease had Expanded Disability Status Scale (EDSS) scores of 4.0 or less (self-sustained, fully ambulatory), whereas the majority of patients with progressive disease types had EDSS scores of 6.0 or greater (at least unilateral assist for walking). These findings emphasize the importance of early intervention in patients with relapsing disease to slow or prevent the accumulation of physical disability associated with progressive types of disease. Progressive disease was associated with lack of full-time employment and being disabled before the age of 60 years. Patients with relapsing disease were more likely to be employed and have private forms of insurance, whereas patients with progressive types of disease were more likely to have government-supported insurance to cover medical expenses.

Tissue plasminogen activator for acute stroke in everyday clinical practice.

Thrombolysis for acute ischemic stroke has become a reality. The aim of our study was to assess the opportunity and practicality of establishing acute stroke treatment in a hospital that did not participate in acute stroke treatment trials, as well as to prospectively analyze 2 groups of patients who reached the Emergency Department (ED) within 3 hours who were either treated or not treated with tissue plasminogen activator (t-PA). The average score for severity of neurological deficits for the patients who received t-PA was 14 on the National Institute of Health Stroke Scale (NIHSS). We compare this group with 18 patients who did not receive t-PA but had similar NIHSS scores (13.9 average). Both groups were matched for age and other comorbidity factors. We concluded that the establishment of an acute stroke treatment algorithm is possible de novo in a hospital that is equipped with computed tomography (CT) and neurosurgery services. The number of patients who can receive t-PA treatment is limited by the strict inclusion and exclusion criteria. Prolonged door-to-needle time was caused by delays in CT interpretation, processing of laboratory results, and stabilization of blood pressure. Patients who received t-PA had a shorter length of stay, were more independent, and had a better survival rate after 1 year. Our findings were in agreement with the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Study that led to the approval of the use of t-PA in the treatment of acute ischemic stroke.

The CVC removal distress syndrome: an unappreciated complication of central venous catheter removal.

The removal of a central venous catheter (CVC) can be complicated by rare but potentially life-threatening neurocardiopulmonary distress. The clinical courses of eight patients who had CVC removal complications are reviewed. Seven patients had catheter removal from the right internal jugular vein, and one from the right subclavian vein. The complications occurred after complete removal of the catheter (four patients), after guidewire replacement for catheter change (three patients), and after detachment of the hemostasis side port of the Swan introducer during sheath removal (one patient). Each of them had more than one complication. The major complications were: neurologic paresis or coma (four patients), respiratory failure (four patients), and shock (two patients). One patient died of pulmonary sepsis. The overall mortality rate was 12.5 per cent. Guidelines for safe removal of central venous catheters are proposed. Possible mechanisms of the complications are discussed. We refer to the observed complications as the CVC removal distress syndrome.

Cardiac arrest caused by trigeminal neuralgia.

A 67-year-old man with a 12-year history of trigeminal neuralgia experienced multiple fainting episodes preceded by right facial pain. One episode resulted in cardiac arrest with successful resuscitation. Pacemaker insertion prevented further episodes of syncope despite the occurrence of pain. The fainting episodes and cardiac arrest are believed to be unusual manifestations of trigeminal neuralgia.

Modified Brown-Séquard syndrome following coronary artery bypass graft: case report.

A 75 year old man underwent a triple coronary artery bypass graft performed with intra-aortic balloon pump assistance. Left leg weakness developed on the first postoperative day, progressive worsening occurred over the next 2 1/2 weeks, finally culminating in a modified Brown-Séquard pattern of deficit. No etiology was found. Previous reports of spinal cord injury following coronary artery bypass graft are reviewed and the microcirculation of the spinal cord is discussed.